Actively Recruiting Studies

This page features extramurally funded clinical trials supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Click on a disease/condition below to find studies that are actively recruiting. Updates are made to this page as new studies get funded and begin recruitment. Please check back often to find new trials supported by NIAMS.

Please check other clinical trials supported by the NIAMS that have completed recruitment or completed with published results following the links below.
View Active Studies with Completed Recruitment
View Completed Studies with Published Results

For questions, please contact the NIAMS Clinical Trials team at: NIAMSclinicaltrials@mail.nih.gov

Disease / Condition

 

Actinic Neoplasia

Photodynamic Therapy-Induced Immune Modulation: Part III

Numerous environmental and iatrogenic pro-oxidative stressors ranging from chemotherapy to ultraviolet radiation have been demonstrated to induce immunosuppression in preclinical murine (mouse) models. These stressors have also been shown to be potent inducers of the lipid mediator platelet-activating factor (PAF), which exerts immunosuppressive effects in murine mouse models. The previous work has characterized the exact pathways by which PAF-dependent immunosuppression occurs and have identified a major role of regulatory T cells (Treg). PAF released from injury acts upon the mast cell PAF receptor resulting in the formation of immunosuppressive Tregs. This process is dependent upon the cytokine IL-10 and cyclooxygenase-2 (COX-2) generated prostaglandins. Though high levels of PAF has been shown to be generated in humans in response to many of the immunosuppressive stressors that induce PAF in animal models, studies are needed to define if this PAF COX-2Treg pathway is functional in humans.

The study team has found that topical photodynamic therapy (PDT) is a very potent inducer of PAF in murine skin and induces systemic immunosuppression only in mice expressing PAF receptors. Therefore, this study is designed to test if the PAF COX-2 Treg pathway is involved in PDT-induced effects and could be pharmacologically modulated with COX-2 inhibitors to block the immunosuppression and potentially improve PDT efficacy in treating precancerous actinic keratoses lesions

View more about this trial in ClinicalTrials.gov

Anterior Cruciate Ligament (ACL) Injury 

Real-time Sensorimotor Feedback for Injury Prevention Assessed in Virtual Reality

Traumatic and debilitating anterior cruciate ligament (ACL) injuries occur at a 2- to 10-fold greater rate in female than male athletes, and 50-100% of females develop knee osteoarthritis within 12-20 years of initial injury. The National Public Health Agenda for Osteoarthritis recommends expanding and refining evidence- based prevention of ACL injury to reduce this burden. The study team has identified modifiable risk factors that predict ACL injury in young female athletes. The lab-based neuromuscular training targets modifiable risk factors and shows statistical efficacy in high-risk athletes, but a meaningful risk re-categorization to "low-risk" has not been achieved.  The overall objective of this proposal is to implement and test innovative augmented neuromuscular training (aNMT) methods to enhance sensorimotor learning and more effectively reduce biomechanical risk factors for ACL injury.

View more about this trial in ClinicalTrials.gov

 

A Two Arm Non-Inferiority Randomized Clinical Trial Comparing ACL Repair with BEAR Device vs. Autograft Patellar Tendon ACL Reconstruction (BEAR – MOON Trial)

Tissues which live within joints, including the anterior cruciate ligament, rotator cuff tendon, meniscus and labrum fail to heal spontaneously after injury and have high failure rates of surgical repair. The ACL represents a good model to study the problem of intra-articular healing as there are validated preclinical models and clinical outcome measures that make it possible to critically evaluate the success or failure of strategies to enhance tissue healing. The current standard of care for ACL injuries is ACL reconstruction, which is good at stabilizing the knee but requires compromising other uninjured structures around the knee to obtain a graft that is subsequently used to replace the ACL. Further the early posttraumatic OA is not mitigated despite ACL reconstruction. The preclinical studies on ACL repair called BEAR (Bridge-Enhanced ACL Repair) demonstrated a prevention of posttraumatic OA and achieved knee stability. The positive preclinical findings of BEAR compared to ACL reconstruction provided the foundation for two FDA approved preliminary clinical trials: 1) the first-in-human cohort study (“BEAR I”), and 2) a small, single-center randomized control trial (“BEAR II”). The statistical analysis of our pilot data shows a 200 patient trial will be required to demonstrate non-inferiority of BEAR (a novel paradigm changing technology) when compared to ACL reconstruction (current gold standard) for the key outcomes of anterior-posterior (AP) knee laxity and a validated patient reported outcome for knee surgery. Therefore, the study team proposes the BEAR-MOON (Bridge-Enhanced ACL Repair) multi-center randomized non-inferiority clinical trial for co-primary outcomes AP (anterior-posterior) knee laxity and International Knee Documentation Committee (IKDC) validated patient reported outcome measure.

View more about this trial in ClinicalTrials.gov

 

STABILITY 2: ACL Reconstruction +/- Lateral Tenodesis with Patellar vs. Quad Tendon

Anterior cruciate ligament reconstruction (ACLR) is complicated by high failure rates in young active individuals. The surgical methods to reconstruct the ACL-deficient knee, including graft selection (autograft bone-patellar tendon-bone or quadriceps tendon) and performance of a lateral extra-articular tenodesis may reduce the risk of graft failure in young active individuals. Improved surgical methods to reduce the risk of graft failure will minimize the need for revision ACLR and the associated decreased quality of life and socioeconomic burden that occurs because of ongoing knee instability and the increased risk for post-traumatic osteoarthritis.

View more about this trial in ClinicalTrials.gov

Anti-Phospholipid Syndrome

Certolizumab to Prevent Pregnancy Complications in High-Risk Patients With APS or SLE - (IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy)

Antiphospholipid syndrome (APS) is an autoimmune disorder that occurs most commonly in women of reproductive age and is associated with thrombosis and adverse pregnancy outcomes (APOs), such as fetal loss and preterm birth due to severe preeclampsia (PE) or placental insufficiency (PI). Traditional therapy for APS during pregnancy has been a heparin agent and low dose aspirin. However, in PROMISSE, a prospective observational study of 724 patients, 44% of pregnancies in women with APS and LAC resulted in APOs despite treatment with heparin and low dose aspirin.

Based on the observations in PROMISSE, this study hypothesizes that tumor necrosis factor-alpha blockade will significantly decrease the rate of fetal death and preterm delivery due to PE and PI in women with APS and LAC.

View more about this trial in ClinicalTrials.gov

Atopic Dermatitis

JAK Inhibition in Down Syndrome

People with Down syndrome (DS) display profound immune dysregulation, which could have myriad negative impacts on their health, including the development of various immune and neurological disorders. Multiple lines of evidence indicate that hyperactivation of interferon (IFN) signaling drives immune dysregulation in DS. This study aims to complete a clinical trial in adults with DS and immune skin conditions, using a pharmacological inhibitor of IFN signaling, which is expected to have multidimensional therapeutic benefits in this population.

View more about this trial in Clinical Trials.gov

Chronic Pain

GET Living: Graded Exposure Treatment for Children and Adolescents with Chronic Musculoskeletal Pain

With up to a third of adolescents reporting recurrent or chronic musculoskeletal pain, it is a critical national health problem. The experience of chronic pain in adolescence negatively impacts overall health during this important life period and increases the risk of pain and mental health problems in adulthood. Pain-related fear is repeatedly identified as an important factor that increases the likelihood of poor outcomes among adolescents with pain, and yet pain-related fear is rarely targeted in typical pain management (TPM). Perhaps unsurprisingly, TPM yields no change in pain-related fear, and modest improvements in functional disability. To overcome limitations of TPM for pain-related fear, graded in-vivo exposure treatment (GET) was developed. While TPM focuses on pain control via pain management psychology and impairment-based physical therapy, GET is jointly delivered by a pain psychologist and physical therapist targeting functional improvement, through exposing patients to activities previously avoided due to fear of pain. GET is successful in adults with chronic musculoskeletal pain! and our pilot data of GET for adolescents with chronic pain (GET Living) is robust, with significant declines in patient fear, activity avoidance, and disability. Uniquely, GET Living also targets parent distress and behavior, and our pilot data demonstrate decreases in parent fear, avoidance, and protective behavior. GET Living also distinguishes itself with an innovative assessment approach to patient progress and clinical endpoints. In addition to standard assessment tools, GET Living utilizes electronic daily diary technology to identify exactly when improvements in outcomes are occurring/not occurring, and objective biomechanical assessment using motion analysis and physical activity monitoring via Actigraphy.

View more about this trial in ClinicalTrials.gov

Chronic Low Back Pain

Proof of Concept Study to Treat Negative Affect in Chronic Low Back Pain

This study addresses the need for better evidence-based pain treatment for patients with chronic low back pain (CLBP) who have co-occurring negative affective disorders, such as major depression with anxious features. The CLBP subgroup with comorbid depression or anxiety disorders (commonly termed, high negative affect) is approximately 20-30% of the 50 million adults with CLBP in the United States. This subgroup is particularly refractory to pain treatment and is in desperate need of better non-opioid, comprehensive pain treatment options. Patients with CLBP and high levels of negative affect (NA) suffer higher levels of pain and have worse disability and function. Due to these factors, they have been prescribed opioids more frequently and misuse opioids at a much greater rate (40-60% rates of non-adherence), which is related to self-medication of depression and anxiety by taking extra opioids. Poor pain management in patients with high NA is due in part to a lack of more effective evidence-based treatment options to improve pain, depression, anxiety, and function, and prevent opioid misuse.

View more about this trial in ClinicalTrials.gov

Fibromyalgia

Multi-site Randomized Clinical Trial of FIT Teens for Juvenile Fibromyalgia

Juvenile-onset fibromyalgia (JFM) is a chronic, debilitating pain condition that persists into adulthood for the majority of patients. The previous research has demonstrated that cognitive-behavioral therapy (CBT) is effective in reducing functional disability in adolescents with JFM. However, in order to achieve stronger and clinically meaningful improvement in functional disability and reduce pain, changing sedentary behavior and increasing engagement in moderate-vigorous physical activity is a crucial component of JFM pain management. Incorporation of physical exercise has emerged as a logical next step to enhance CBT, yet regular participation in any physical activity is difficult to initiate and maintain in JFM patients.

This study evaluates whether Fibromyalgia Integrative Training program for Teens (FIT Teens), a combined cognitive behavioral therapy and neuromuscular exercise training program are more effective in reducing disability in adolescents with Juvenile Fibromyalgia compared to CBT alone or a graded aerobic exercise (GAE) program alone.

View more about this trial in ClinicalTrials.gov

 

Mechanisms and Modification of Pain Modulatory Capacity

Chronic pain affects over 100 million Americans, with an annual cost estimated at over $500 billion. Reliance on opioid medications has led to an “opioid crisis” and the need to identify alternative treatment for chronic pain. This study hypothesizes that chronic pain represents failure or suboptimal function of pain modulatory capacity (PMC) and aims to test hypotheses about resilience to clinically relevant pain challenges, and test multisystem (psychological, behavioral, and neural) mechanisms underlying chronic pain. Furthermore, the study aims to demonstrate the trainability of PMC in asymptomatic controls, which has relevance for pain prevention, and in patients with fibromyalgia (FM) who are hypothesized to have suboptimal PMC (resilience) to pain challenges.

View more about this trial in ClinicalTrials.gov

 

Fibromyalgia TENS in Physical Therapy Study (FM-TIPS) (FM-TIPS)

Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain, tenderness, and stiffness associated with fatigue and sleep disturbance. The goal of reducing opioid use in patients with chronic pain requires that proven non-pharmacological treatments are applied in clinical practice. The study team has recently completed the FAST (Fibromyalgia Activity Study with TENS) trial demonstrating the efficacy of Active Transcutaneous Electrical Nerve Stimulation (TENS) compared with Placebo TENS or No Treatment in women with FM.  While physical therapists are trained in the use of TENS, it is underused in clinical practice. This study proposes to conduct an embedded pragmatic trial to compare the effectiveness of physical therapy with or without the addition of TENS for FM patients within physical therapy (PT) practices as the study sites.

View more about this trial in ClinicalTrials.gov

Granulomatosis with Polyangiitis (GPA)

Abatacept (CTLA4-Ig) for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (Wegener's) (ABROGATE)

Granulomatosis with polyangiitis (Wegener’s) (GPA) is a systemic inflammatory disease that is characterized by necrotizing, granulomatous inflammation and vasculitis of the small to medium-sized vessels. Despite the availability of medications that can induce remission, disease relapses occur in up to 75% of patients with GPA. The majority of these relapses are not severe, but can nevertheless result in incremental significant morbidity, from both GPA and the use of immunosuppressive treatment required to manage such relapses.   Abatacept (CTLA4-Ig) is comprised of the ligand-binding domain of CTLA4 plus human immunoglobulin. Through this construct abatacept carries the potential to modulate the costimulatory signal required for T cell activation. Based on laboratory data supporting a potential role for activated CD4 T cells in the pathogenesis of GPA, an open-label study was conducted to examine the role of abatacept in non-severe relapsing GPA. In 20 GPA patients treated with abatacept, 90% improved, 80% achieved remission, and 70% reached common closing. Eleven out of 15 patients were able to discontinue prednisone.

This multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of abatacept to achieve sustained glucocorticoid-free remission in patients with relapsing non-severe GPA.

 View more about this trial in ClinicalTrials.gov

 

The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach

Granulomatosis with polyangiitis (Wegener’s) (GPA) is a primary systemic vasculitis, predominantly involving microscopic blood vessels with no or scanty immune deposits. GPA is strongly associated with circulating auto-antibodies to neutrophils (ANCA) and is one of a group of conditions known as ANCAassociated vasculitis (AAV). The cause of AAV is unknown. AAV has an annual incidence of 20 per million and an approximate prevalence of 200/million. It is a multi-system autoimmune disease that causes tissue damage especially to the respiratory tract and kidneys and causes early mortality, organ failure including end-stage renal disease, and chronic morbidity. Prior to the availability of effective treatment, AAV was almost universally fatal, with a 93% mortality within 2 years due to pulmonary and renal failure. Administration of cytotoxic immunosuppression (cyclophosphamide, rituximab, methotrexate) and glucocorticoids (GC) for at least one year induces remission in approximately 80% of patients. GC are a standard of care in the treatment of AAV. High doses of GC early in disease although undeniably reduce disease activity due to their anti-inflammatory and immunosuppressive properties also increase the risk of infection particularly in the elderly and in the presence of uremia. There is a major unmet need for safer therapy that leads to sustained treatment free remission in patients with relapsing disease, which will reduce drug toxicity that results from cumulative exposure to immunosuppression and glucocorticoids.

This randomized controlled trial aims to evaluate the effects of using low-dose glucocorticoids as compared to stopping glucocorticoid treatment entirely.

View more about this trial in ClinicalTrials.gov

Hand Osteoarthritis

A Pilot Randomized Controlled Trial of Hand Traction for Nodal Osteoarthritis

Hand osteoarthritis (OA) is a common problem and is associated with substantial functional limitations. To date, few therapies are effective in reducing pain in hand OA; and most are only based on expert opinion. Although nodal hand OA has traditionally not been viewed as a biomechanically driven disease, there is growing evidence that indeed it is. OA in the knee, a disease long known to be biomechanically driven, can be treated with distraction, a therapy where external hardware is surgically placed preventing joint motion, providing intra-articular negative pressure, and increasing the joint space. People awaiting knee total knee arthroplasty receiving distraction have reduced pain, growth of new articular cartilage, and delay and sometimes complete avoidance of arthroplasty. Unfortunately, distraction is associated with serious attendant adverse events including a 10% rate of pulmonary emboli despite anticoagulation and an 85% rate of pin site infection, limiting the widespread use of this treatment. Nevertheless, it is an important proof of concept that unloading an OA joint may allow structure and symptom improvement. Since distraction has both symptom and structure benefits in knee OA, then traction therapy, using non-invasive finger traps, may have similar benefits for hand OA without attendant complications. Thus, this study proposes a pilot randomized controlled trial of traction on 100 participants recruited from the Michael E. DeBakey VA Medical Center with at least 3 joints affected by distal interphalangeal (DIP) nodal hand OA, with at least one symptomatic joint.

View more about this trial in ClinicalTrials.gov

Isolated Skin Vasculitis

A Randomized Multicenter Study for Isolated Skin Vasculitis

Vasculitides are uncommon diseases which can affect almost any organ. Vasculitis frequently involves the skin, as an isolated process, or as part of systemic vasculitis. Skin vasculitis represents an important source of morbidity and symptomatology as well as an opportunity for early diagnosis and treatment. Despite the important place of isolated skin vasculitis in this group of diseases, there has historically been limited emphasis placed on understanding its pathogenic mechanisms and determining its best treatment. Whereas episodes of isolated small vessel vasculitis in the skin are often self-limited, resolve over 3-4 weeks with residual hyperpigmentation, and do not recur, up to one-third of patients have persistent or recurrent disease for up to several years. The cutaneous vasculitic lesions can be itchy, painful, and cosmetically disturbing. It can ulcerate, and then be complicated by infection and scarring. In around 8-10% of patients, chronic or recurrent small vessel vasculitis can develop. In general, systemic involvement (if found) is minimal and limited to mild arthralgias, myalgias, fatigue, low-grade fever or peripheral edema. No therapy has been proven to shorten the duration of disease or decrease its severity and the frequency of the flares.  Initial long-term treatment options mainly include colchicine, dapsone, or azathioprine.

This study proposes to compare the efficacy of three of the drugs among the most commonly used ones — colchicine, dapsone, and azathioprine — for the treatment of isolated skin vasculitis, in a multi-center sequential multiple assignment randomized trial.

View more about this trial in ClinicalTrials.gov

Knee Arthroplasty

Improving Physical Activity and Gait Symmetry After Total knee Arthoplasty

Total knee arthroplasty (TKA) is one of the most common surgical procedures performed in the U.S., and rates are rising rapidly. TKA results in decreased pain, increased range of motion, and improvements in some aspects of physical function for most patients. However, accumulating evidence shows that patients have persistent deficits in other critical outcomes following TKA. First, the majority of patients do not substantially increase physical activity beyond levels prior to TKA, remaining well below recommended levels. This has negative implications for both joint health and overall health. Second, gait asymmetries are common following TKA, such that patients often continue to load the non-surgical leg more heavily during walking, even when the post-surgical leg is pain free, placing the contralateral limb at risk for developing or worsening osteoarthritis. The long-term objective of this study is to improve post-TKA outcomes, particularly overall physical activity and joint loading symmetry, through implementation of a rehabilitation process that directly addresses these core domains.

View more about this trial at ClinicalTrials.gov

Knee Osteoarthritis

The Relation of Altered Pain Processing to Impact Loading and Response to a Gait Retraining Treatment in Knee Osteoarthritis

Knee Osteoarthritis (OA) is a major public health problem, causing substantial pain and functional limitations and effects ~12% of older adults. There are a few effective non-invasive treatments to prevent disease progression or decrease pain. The current proposal will provide evidence-based information in order to design novel and effective rehabilitation treatments for knee osteoarthritis.

View more about this trial at ClinicalTrials.gov

A Sequenced-Strategy for Improving Outcomes in Patients with Knee Osteoarthritis Pain

Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability worldwide, affecting over 30% of older adults and represents a major global health and economic burden to individuals and society. The rates of KOA have more than doubled in the past 70 years and continue to grow sharply, given increases in life expectancy and population BMI. Surgery is often employed to treat KOA, but it is associated with a high rate of persistent pain and is not a permanent solution. Numerous nonsurgical therapies have been advocated to treat pain in patients with KOA. However, stand-alone conservative treatments including non-opioid medications and joint injections provide only limited pain relief and functional improvement in a subset of knee OA sufferers. This has led to a high rate of opioid use in this population. The overarching goal of this proposal is to conduct a sequential parallel group randomized controlled trial (RCT) to rigorously evaluate the comparative-effectiveness of conservative behavioral and non-opioid pharmacological treatments (Phase I) and, among non-responders, the benefits of nonsurgical procedural interventions (Phase II) in three interrelated Aims.

View more about this trial in ClinicalTrials.gov

Knee Replacement

Reducing Sedentary Time Using an Innovative mHealth Intervention Among Total Knee Replacement Patients

The number of individuals undergoing total knee replacement (TKR) each year continues to rise. While TKR is effective for improving pain and function, subsequent improvements in physical activity are not common. As a result, patients spend most of their day engaged in sedentary behavior, which may put them at higher risk of experiencing poor function and disability, as well as lower the overall success of the surgical treatment. Intervening on sedentary time, rather than physical activity, may be a more feasible first-step approach for modifying activity-related behaviors in this population. Therefore, the purpose of this innovative clinical trial is to use TKR as a teachable moment for implementing a sedentary reduction intervention. This study proposes to use a just-in-time mobile health (mHealth) intervention to reduce sedentary time among TKR patients.

View more about this trial at ClinicalTrials.gov

Low Back Pain

Randomized-controlled trial of virtual reality for chronic low back pain to improve patient-reported outcomes and physical activity

Chronic low back pain is a prevalent and costly condition that impairs physical, emotional, and social function. Therapeutic virtual reality (VR) has emerged as a promising and evidence-based treatment modality for acute and chronic pain. This study will test the impact of VR on chronic lower back pain management and measure whether it can improve pain, reduce opioid use, and improve quality of life.

View more about this trial in ClinicalTrials.gov

Meniscal tear and Osteoarthritis (OA)

Treatment of Meniscal Problems in Osteoarthritis

Knee osteoarthritis is a disabling problem affecting over 15 million adults in the United States. Many people who have knee arthritis also experience painful meniscal tears. There are a number of different treatments that can be used to manage meniscal tears in the presence of knee arthritis. Treatments include surgically removing the damaged part of the meniscus; strengthening exercises to improve pain and function; manual therapy including massage and mobilization; acupuncture; and others. The combination of surgery and exercise therapy was long thought to be the best treatment. However, recent studies have shown that surgery followed by physical therapy is no more effective than physical therapy by itself.

While physical therapy alone has been shown to result in similar pain relief as arthroscopic surgery, researchers have not yet done studies to determine what type of physical therapy is best for people with knee arthritis and meniscal tears. This study proposes the TeMPO (Treatment of Meniscal Problems in Osteoarthritis) Trial to compare different non-operative physical therapy regimens to gain a better understanding of how physical therapy works and what regimen will best reduce pain and improve function in persons with meniscal tear and osteoarthritis.

View more about this trial in ClinicalTrials.gov

Osteogenesis Imperfecta

Rare Diseases Clinical Research Network Brittle Bone Disease Consortium Longitudinal Study of Osteogenesis Imperfecta

Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. The purpose of this natural history study is to perform a long-term follow-up of a large group of people with osteogenesis imperfecta (OI) to improve the health and quality of life of people with OI.  The study team will collect information on medical history, number of broken bones, surgeries done, medications taken, ability to walk, pain, lung function and breathing, hearing, and bone mineral density. This study aims to perform DNA testing and collect natural history data on all individuals enrolled in this longitudinal study, see how often people with type I OI have vertebral compression fractures of the spine, follow people with all forms of OI to see how often they develop scoliosis (curvature of the spine), and look at dental health in people with OI.

View more about this trial in ClinicalTrials.gov

Osteoporosis

Mechanisms Underlying the Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration

One in three women and one in five men will experience an osteoporotic fracture during their lifetime. Currently, available medications reduce fracture risk but are unable to fully restore skeletal integrity. Thus, there remains an urgent need for osteoporosis treatments that rapidly and effectively restore bone strength. Unlike most chronic conditions, osteoporosis has historically been treated with only one drug at a time. Attemps to combine anabolic agents with the most commonly used antiresorptive agents (bisphosphonates) did not prove efficacious. In contrast, we recently reported that the combination of teriparatide and the receptor activator of nuclear factor-kB ligand (RANKL) inhibitor, denosumab, increases bone density and improves bone microarchitecture and estimated strength more than either drug alone and more than any vailable therapy. The study team has hypothesized that the efficacy of this combination is dependent on denosumab's capacity to fully block teriparatide's stimulation of bone resorption while allowing for teriparatide-induced stimulation of bone formation (modeling-based bone formation). In this proposal, the study team will directlyl assess the ability of teriparatide to stimulate modeling-based bone formation with bone resorption is blocked by denosumab.

View more about this trial in ClinicalTrials.gov

Osteosarcopenia

Effect of a Ghrelin Receptor Agonist on Muscle and Bone

Adults with low muscle mass also usually have low bone mass, making them vulnerable to falls, fractures, and other injuries. This study will determine the effectiveness of treatment with a ghrelin receptor agonist in improving short term indicators of muscle and bone health in adults with low bone and muscle mass. The results of this trial will inform the design of a larger definitive randomized trial designed to establish efficacy.

View more about this trial in ClinicalTrials.gov

Pelvic Fractures

PTH(1-34) and Pelvic Fracture Healing - a Randomized Controlled Trial

This randomized, double-blind, placebo-controlled 3-month study tests the efficacy of teriparatide (TPTD) to accelerate fracture healing in women and men ≥ 65 years of age with acute fractures of the pelvis.  The investigator hypothesizes that TPTD for 3 months as an adjunctive therapy in addition to standard of care will accelerate radiographic evidence of fracture healing and functional recovery and that differences between TPTD and placebo groups documented at 3 months of treatment will persist when evaluated up to 12 months. 

View more about this trial in ClinicalTrials.gov

Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable and inherited mechano-bullous disease of the skin characterized by skin fragility, blister formation, and chronic wounds. RDEB is caused by mutations in the COL7A1 gene encoding type VII collagen (C7), the major component of anchoring fibrils (AFs) that anchor the epidermis to the dermis. AFs are attenuated, diminutive, or absent in RDEB. There is no effective treatment for RDEB except palliative measures and supportive wound care.  Based on encouraging in vitro and in vivo RDEB data, the proposed study will assess the safety and efficacy of IV gentamicin in RDEB patients with nonsense mutations.

View more about this trial in ClinicalTrials.gov

Rheumatoid Arthritis

Skeletal Muscle Dysfunction in Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, with a prevalence of 1% worldwide. Nearly two-thirds of RA patients suffer from loss of skeletal muscle mass, which often co-occurs with central obesity, a feature of metabolic syndrome. Lower muscle mass leads to muscle weakness, a major contributor to physical impairment in patients with RA, even after multivariate adjustment for demographic and disease variables. The overarching goal is to understand at a mechanistic level the metabolic and physiologic abnormalities of skeletal muscle in patients with RA and to use that knowledge to improve therapy for skeletal muscle dysfunction in RA.  Thus, this study hypothesizes that increased lipid content in skeletal muscle contributes to insulin resistance and impaired skeletal muscle homeostasis and function in RA and that treatment with pioglitazone will improve muscle function by decreasing lipid deposition in skeletal muscle, restoring the anabolic effects of insulin and attenuating inflammation.

 View more about this trial in ClinicalTrials.gov

 

Cell-Based Therapy in Rheumatoid Arthritis: Proof of Concept Phase 1 Trial

Rheumatoid Arthritis (RA) affects adults in the prime of their life and their career with two peaks of onset, the first in the mid-life around the age of forty and the second in the sixties. RA affects women more frequently than men with up to 1% of the population affected. The burden to society includes but is not limited to the potential loss of individuals who are at the peak of their careers themselves who may be affected by RA or who may be responsible for caring for a family member with RA. This Phase I clinical trial in which RA patients have had an incomplete response to methotrexate receive add on therapy with a single infusion of adult bone marrow stem cells (or placebo infusion) from a healthy donor to “quiet” the immune system. If successful, cell-based therapy would represent a paradigm shift in the treatment of RA. Studies have demonstrated that early treatment of new-onset RA improves outcomes, but therapies are most often life long, expensive and have undesirable side effects. If immune tolerance can be induced and the immune system "reset" to its "pre-RA" condition, then environmental, and other lifestyle changes (e.g., quitting smoking) could be used to reduce the chance of recrudescence of RA and increase the interval to "flare."

View more about this trial in ClinicalTrials.gov

 

Treatments Against RA and Effect on FDG-PET/CT (The TARGET Trial)

Rheumatoid arthritis (RA) is a chronic inflammatory disease, causing joint damage and disability. While remarkable progress in the treatment of RA over the past two decades has improved many outcomes, mortality rates in RA remain 1.5-3-fold above non-RA controls. Cardiovascular disease (CVD) is the leading cause of excess deaths in RA.  Most experts believe that enhanced vascular inflammation underpins accelerated atherosclerosis and CV events yet, there has been no direct proof for this hypothesis. If this is true, then RA therapies that reduce joint inflammation might also reduce CV risk. The lack of an RA-specific CV risk tool hampers evidence-based guidelines, as general population tools perform poorly in RA. These gaps in knowledge create uncertainty for patients and providers in managing RA and its comorbidities. This study proposes to use 18fluoro-deoxyglucose by positron emission tomography/computed tomography (FDG PET/CT) as a novel imaging modality to detect baseline, and disease-modifying antirheumatic drug (DMARD)-associated changes in, vascular inflammation in RA.

View more about this trial in ClinicalTrials.gov

 

Weight loss and exercise to improve rheumatoid arthritis cardiovascular risk

Despite recent, revolutionary improvements in pharmacologic management, rheumatoid arthritis (RA) remains associated with increased rates of cardiovascular disease and mortality. RA cardiovascular risk results from a combination of traditional risk factors and RA-related systemic inflammation. Consequently, to improve overall RA cardiovascular risk, efforts should target both traditional risk factors and inflammation. One hypothetical means of improving overall RA cardiovascular risk is through weight loss and physical activity. Together, weight loss and physical activity can improve traditional cardiometabolic health through fat mass loss and skeletal muscle quality and functional gains. Additionally, disease-related cardiovascular risk will improve as both fat mass loss and exercise reduce systemic inflammation.

This study will explore whether a supervised intervention with weight loss and exercise training improves objective assessments of RA cardiovascular risk, disease activity and results in patients reporting overall improved health.

View more about this trial in ClinicalTrials.gov

Sedentariness

Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Physical inactivity is a major public health challenge underlying a broad range of health problems at all ages. While physical activity (PA) has shown to produce relevant health benefits, the underlying molecular mechanisms are poorly known. The coordinated effort of clinical and animal studies supported by bioinformatics and chemical analyses will achieve the Molecular Transducers of Physical Activity Consortium (MoTrPAC) goals of assessing the molecular changes that occur in response to PA. The Consortium Coordinating Center (CCC) for the MoTrPAC will provide support for the organization, administration, planning, standardization, documentation, monitoring and reporting activities relating to the MoTrPAC. The CCC will play a pivotal role in ensuring the cohesion of the MoTrPAC by enhancing communication and integration across all study components, including the Clinical Sites, the Preclinical Animal Study Sites, the Bioinformatics Center, the Chemical Analysis Sites, and the various study committees. The CCC will develop strategies and strategic planning processes by integrating activities of the MoTrPAC investigators and facilitate interactions and communications with junior and senior investigators outside the consortium to maximize the use of the MoTrPAC resources toward achieving the overall research goals. To accomplish these goals and maximize the progress and productivity of the MoTrPAC, the CCC will promote team science, team leadership, and innovative leadership approaches across all study components. Strategic planning that follows the principles of the dynamic theory of strategy will be fostered to evaluate alternative approaches, maintain the cutting-edge scientific focus, leverage state-of-the-art coordination technologies, anticipate challenges, and maximize future opportunities to ensure the success of the consortium.

View more about this trial in ClinicalTrials.gov

Spinal Cord Injury

Exploration of blood flow regulation to bone in humans

Without blood flow, bone cannot maintain its integrity. Bone blood flow responds to various local and systemic factors, however, bone perfusion in humans remains relatively unstudied. This study will investigate key mechanisms that regulate bone perfusion in able-bodied and contrast responses to those with spinal cord injury (SCI). SCI is a model of chronic reduced loading with loss of sympathetic regulation.

In tibial cortical bone, the study team will: 1) determine the impact of compressive loading with and without muscle contractions; 2) determine the impact of vascular sympathetic activity and systemic perfusion pressure; 3) compare the response between able-bodied and those with SCI

View more about this trial in Clinical Trials.gov

Statin-Induced Inhibition of Skeletal Muscle Adaptation to Exercise

Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity

More than 40 million Americans currently take statins for the treatment or prevention of hyperlipidemia and cardiovascular disease (CVD). Patients taking statins are also commonly advised to exercise regularly to further lower the risk for metabolic and cardiovascular disease. However, recent evidence suggests that statins can impair important exercise adaptations and that this, again, may occur as a result of statins negatively impacting mitochondria in skeletal muscle. Understanding how long-term statin therapy affects mitochondrial function in skeletal muscle is extremely important clinically, given the critical role skeletal muscle plays in maintaining metabolic and cardiovascular health. Therefore, the objectives of this study are to determine the impact of statin therapy on skeletal muscle mitochondrial function, cardiorespiratory fitness, and metabolism in humans.

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Systemic Lupus Erythematosus (SLE)

Study of Anti-Malarials in Incomplete Lupus Erythematosus

Systemic lupus erythematosus (SLE) causes major organ damage and shortens lifespan in relatively young persons. Early diagnosis and treatment are essential to improving outcomes for SLE patients. However, evidence-based approaches to early treatment interventions and the appropriate target population for these interventions are not available. We propose that individuals who have positivity for antinuclear antibodies (ANAs) and who also exhibit some of the other features that are used to classify SLE, are at high risk of progressing to the full systemic form of this disease. These individuals, who have significant levels of ANA with 1 or 2 additional items from the lupus classification criteria, are considered to have incomplete lupus erythematosus (ILE).

The primary objective is to determine whether HCQ treatment can prevent acquisition of additional clinical and immunologic features that define SLE. The secondary objectives are to determine whether HCQ treatment 1) lessens lupus disease activity as measured by standard scoring indices, 2) improves patient-reported outcomes, 3) prevents accumulation of immunologic abnormalities including autoantibodies and cytokines, and 4) has an acceptable toxicity profile.

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Lupus Intervention for Fatigue Trial

Systemic lupus erythematosus (SLE, lupus) is a systemic autoimmune disease characterized by pronounced inflammation that affects up to 1.5 million people in the US. While excess mortality has decreased in SLE patients since the 1970s, a major ongoing cause of morbidity in this population is chronic, debilitating fatigue that significantly decreases quality of life, and increases risk of work disability and associated health care costs. An urgent, unmet need in the management of patients with SLE is identification of effective strategies to reduce fatigue.

Preliminary data from lupus patients showed that regular aerobic exercise can improve quality of life and reduce fatigue. In considering other lifestyle behaviors, there is limited literature on effects of diet, energy balance, and/or nutrient density in SLE patients, but diet intervention has been favorably associated with managing fatigue in other disorders (e.g., cardiovascular disease and age-related functional decline). To study the effects of intervening on these two potential modifiable lifestyle behaviors (PA and diet) this study designed the Lupus Intervention Fatigue Trial (LIFT) to compare the effectiveness of a motivational interviewing program intervention versus a patient educational program control to reduce fatigue in persons with lupus.

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Ulnar Neuropathy

Clinical Trial for Surgery of the Ulnar Nerve (SUN) at the Elbow

Ulnar neuropathy at the elbow (UNE) is a common compressive neuropathy condition that can cause pain, tingling , and muscle loss in hand. If left untreated, it can lead to disability and job loss. Conservative treatment fails in 60% of cases, and most patients require surgery, which is often recommended to eliminate symptoms, but controversy xists over the best procedure. The two most common surgical procedures are in-situ (simple) decompression and subcutaneous anterior transposition. This study plans to conduct a multicenter randomized clinical trial to compare outcomes for two commonly used surgical procedures and develop an optimal surgical plan for individual patients.

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Vasculitis

Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis

Symptoms clearly attributable to inflammatory disease are controllable in the great majority of patients with vasculitis. However, most patients do not feel healthy despite effective immune-suppressive treatment. Among the residual symptoms that disrupt the lives of patients with vasculitis, fatigue, poor physical function, sleep disturbance, and satisfaction with social roles are the most common and have the greatest negative impact on quality of life. Although there are multiple potential sources of these symptoms – residual autoimmune/inflammatory disease, medication side effects, co-morbidities such as obstructive sleep apnea or depression – the cause(s) often defy identification and successful management in the individual patient. Chronic pain is also high on the list of important negative influences on quality of life of patients with vasculitis.

Naltrexone is an opioid antagonist that is used in high doses for emergency treatment of opioid overdose and is FDA approved in an oral daily dose of 50 mg to prevent recidivism in alcoholics. At much lower doses of 4 – 4.5 mg daily, however, it has been shown in small, blinded, randomized trials to improve pain in fibromyalgia, gastrointestinal symptoms in Crohn’s disease, and quality of life in patients with multiple sclerosis.  The mechanism is unclear, with proposals including not only modulation of central pain-processing pathways but also mitigation of inflammatory roles of microglia. In addition to blocking opioid receptors, naltrexone blocks TLR-4, and some studies suggest that the anti-inflammatory effects of low dose naltrexone are independent of opioid receptors.

This multi-center, randomized, double-blinded, cross-over, placebo-controlled trial aims to evaluate the efficacy of low-dose naltrexone (LDN) at 4.5 mg nightly in improving self-reported physical health in patients with vasculitis.

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Venous Leg Ulcers (VLU)

Developing Strategies for Effective Debridement in Patients for Venous Leg Ulcers

Chronic non-healing venous leg ulcers (VLUs) have an intrinsic healing impairment that is associated with dysfunctional gene expression patterns. The previous study has shown that tissue from the non-healing edge of chronic VLUs exhibits characteristic histopathology including epidermal hyperproliferation, dermal fibrosis, accumulation of intracellular pro-collagen and dysregulation of genes involved in epidermal differentiation, migration and proliferation. It also has demonstrated that biopsies taken from the non-healing edges of VLUs before and after debridement have distinct morphologies and distinguishable gene expression patterns, providing the biological basis and justification of debridement. These observations are supported by the findings that primary cells grown from tissue biopsies before and after debridement also have distinct and typical genomic patterns, with cells from pre-debridement edge biopsies exhibiting a non-healing phenotype as evidenced by loss of migration and loss of ability to respond to growth factor stimuli. Moreover, using a genomic approach in a clinical trial to determine mechanism of action of cell-based therapy in patients with VLU, the study team has identified a specific set of genes responsible for therapeutic reprogramming that shifts non-healing ulcer into acute wound-like healing VLU.

The goal of this project is to use genomic profiling, candidate genes and proteins to develop guided surgical debridement to improve healing in chronic non-healing VLUs and to test the efficacy of this approach.

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X-Linked Hypophosphatemia

Calcitriol Monotherapy for X-Linked Hypophosphatemia

X-linked hypophosphatemia (XLH) is characterized by increased FGF23, which impairs activation of vitamin D and promotes renal phosphate wasting leading to osteomalacia and rickets. Current treatment using 1,25- dihydroxyvitamin D(calcitriol) and phosphate is often complicated by hypercalcemia and nephrocalcinosis and does not always prevent hyperparathyroidism. Furthermore, it does not normalize growth. Thus, the study team undertook a pre-clinical study in the Hyp mouse model of XLH, to compare the effects of calcitriol alone vs treatment with FGF23 blocking antibodies on growth, serum and urine mineral ions as well as histological, histomorphometric, microarchitectural and biomechanical properties of bones. These studies revealed that calcitriol monotherapy improves growth, prevents rickets and improves the microarchitectural and biomechanical properties of bone without phosphate supplementation. The beneficial effects of calcitriol were superior to those of the FGF23 blocking antibody employed, perhaps because, as in humans, FGF23 blocking antibodies were not able to sustain increased levels of 1,25-dihydroxyvitamin D. It is notable that the beneficial effects of calcitriol occur in spite of a significant increase in circulating FGF23 and bone FGF23 mRNA expression.

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Last Updated: June 2021