Studies That Have Completed Recruitment
Trials that are no longer recruiting but remain active to complete other study activities are found here. Click on a disease/condition below to learn more about a range of clinical trials studying new and existing interventions for prevention and treatment of arthritis, musculoskeletal and skin diseases.
For questions, please contact the NIAMS Clinical Trials team at: NIAMSclinicaltrials@mail.nih.gov
Disease / Condition
Over the last four decades, these debilitating Injuries have occurred at a 2 to 10-fold greater rate in female compared to male athletes with the highest prevalence occurring between the ages of 16-18 years. As a consequence, there is a large population of females that endure significant pain, functional limitations and knee osteoarthritis (OA) as early as 5 years after the initial unintentional injury. To reduce the burden of OA, The National Public Health Agenda for Osteoarthritis recommends both expanding and refining evidence-based prevention of ACL injury. There currently is a gap in knowledge regarding how to maximize the effectiveness of injury prevention training in young female athletes. The long-term goal is to reduce the ACL injuries in young female athletes. The objective of this study is to increase the efficacy of biofeedback training to reduce the risk of ACL injury. This study tests the central hypothesis that biofeedback methodology is needed to maximize the effectiveness of neuromuscular prophylactic interventions.
Nearly 1 in 60 adolescent athletes will suffer ACL injuries. Approximately 90% of these injured athletes will undergo an ACL reconstruction at an estimated annual cost of $3 billion. While reconstruction and subsequent rehabilitation allow these athletes to return to sports, they have a 15-fold increased risk of secondary ACL injuries, a tear of the ACL graft or the contralateral ACL. As a result, development of an intervention to reduce the incidence of secondary ACL tears would meet a critical need.
The long-term objective of this study is to decrease the number of secondary ACL tears by decreasing side-to-side movement and loading asymmetry. Specifically, this study proposes to evaluate a novel biofeedback training program that focuses on altering loading and movement patterns to improve symmetry and overall lower extremity mechanics in a group of 40 (20 control, 20 intervention) adolescent ACL reconstructed patients.
The loss of skeletal muscle mass, strength, and physical function with age (sarcopenia) has numerous physiological and metabolic consequences that may lead to undesirable outcomes in older adults. Skeletal muscle plays a direct role in force production and its loss can lead to reduced mobility, loss of balance, increased incidence of falls and ultimately disability and loss of independence. In addition, muscle plays an underappreciated role in metabolism and sarcopenia has been associated with insulin resistance and metabolic syndrome. Consequently, identifying interventions that maintain muscle mass and function is a high priority therapeutic goal to improve quality of life and reduce medical costs associated with older adult populations. Dietary intake of the branch-chained amino acid leucine increases the rate of protein synthesis in skeletal muscle through mechanistic target of rapamycin complex 1 (mTORC1)-dependent as well as independent signaling pathways. However, physical inactivity reduces the ability to stimulate muscle protein synthesis in response to amino acids, termed anabolic resistance. Since older adults are at a greater risk of being inactive due to injury, illness or sedentary behavior, it is thought that anabolic resistance to amino acids may contribute to the development of sarcopenia.
Pegloticase is highly efficacious therapy for chronic refractory gout patients. It decreases serum urate (sUA) levels to often undetectable levels and reduces tophi burden. However, its long- term real-world effectiveness is severely limited due to its immunogenicity caused by anti-pegloticase antibody formation. This study investigates the preliminary efficacy and safety of using immune modulating therapy with mycophenolate mofetil (MMF) to prevent immunogenicity conferred by pegloticase.
The primary aims of this trial are to 1) determine if a 12-week course of immune modulating therapy with daily MMF can safely and significantly attenuate immunogenicity to pegloticase as determined by the proportion of participants achieving and maintaining an sUA less than or equal to 6 mg/dL through 12 weeks, compared to concurrent controls, and 2) to assess the incidence and types of adverse events and infusion reaction.
The study aims to develop a rAAVrh74.MCK.GALGT2 as a surrogate gene therapy that can provide significant clinical benefit to boys affected by Duchenne muscular dystrophy (DMD). The study objective is to perform first-in-human studies demonstrating the safety and expression of the vector following intramuscular injection. The central hypothesis is that following intramuscular injection into the extensor digitorum brevis (EDB) muscle, CT antigen expression will be widely identifiable at the sarcolemmal membrane, and no significant inflammation will be seen. The study's specific aims are to perform a first-in-human safety study of intramuscular gene transfer of rAAVrh74.MCK.GALGT2 and to assess the degree of and the effects of CT antigen expression in EDB muscles.
Herpes zoster (HZ), also known as "shingles", is caused by reactivation and multiplication of the ubiquitous varicella zoster virus (VZV) that remains latent in everyone's sensory neurons following varicella, or "chickenpox". Among individuals who live to age 85, the lifetime risk for HZ is 50%, and more than one in five individuals affected by zoster develop post-herpetic neuralgia, resulting in chronic pain. Other serious complications include encephalitis, permanent vision loss, or more rarely, dissemination and death. Fortunately, a live attenuated vaccine is available and can reduce HZ risk by up to 70%. For patients with rheumatoid arthritis (RA), this vaccine has great potential to provide improved quality of life by reducing the incidence and complications associated with zoster. Due to the underlying disease and/or treatments (e.g. steroids) for rheumatoid arthritis (RA), the risk of herpes zoster in RA patients is approximately double in the general population. This increased risk should make prevention of zoster and vaccination exceedingly important for RA patients.
In light of 1) a substantial elevated HZ risk among RA patients; 2) national data showing most RA patients are not vaccinated for HZ; and 3) the high effectiveness of this vaccine in the general population, the investigators propose to conduct the Varicella zostER VaccinE (VERVE) trial, a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and long-term effectiveness of the live herpes zoster vaccine.
Hip fractures occur in 280,000 Americans, over 5,000 per week. During the next 40 years, the number of hip fractures is likely to exceed 500,000 annually, and the estimated annual health care costs will reach a staggering $9.8 billion. Hip fracture patients are at risk of a 30% mortality rate and impairment of independence and quality of life. Hip fractures are commonly treated with a hip replacement, or arthroplasty. Two common types of arthroplasty exist, total hip arthroplasty (THA) and hemi-arthroplasty (HA). Advocates of hemi-arthroplasty (HA) focus upon reduced dislocation rates, lower rates of deep vein thrombosis, shorter operating times, less blood loss, and a technically less demanding procedure. Surgeons supporting THA perceive benefits in improving patient function and improving quality of life. Methodological limitations of previous studies, as well as their small sample sizes and resulting wide confidence intervals, have left the optimal operative approach unresolved.
This study aims to develop and to demonstrate the effectiveness of a systematic, practical, cost-effective diet-induced weight loss and exercise intervention that communities can implement to reduce pain and improve other clinical outcomes in knee OA patients. The primary objective is to determine whether a pragmatic, community-based 18-month diet-induced weight loss and exercise intervention implemented in three North Carolina counties with diverse residential (from urban to rural) and socioeconomic composition significantly decreases knee pain in overweight and obese adults with knee OA relative to an attention control group. Secondary aims will determine whether this intervention improves self-reported function, health-related quality of life, and mobility.
The development of gene therapy has advanced to a point where a cure for Pompe disease can be foreseen. Pompe disease (glycogen storage disease type II; acid maltase deficiency) is a devastating muscle disease resulting from acid alpha-glucosidase (GAA) deficiency in striated and smooth muscle. Despite the availability of enzyme replacement therapy (ERT) with recombinant human (rh) GAA, many patients have poor outcomes including death due to clinically significant anti-GAA antibody response. The limitations of ERT have prompted the preclinical development of gene therapy for Pompe disease. Clinical translation of efficacious gene therapy will greatly advance treatment for Pompe disease by correcting GAA deficiency and suppressing immune responses against rhGAA.
The long-term goal of the study is to develop curative therapy for Pompe disease. Toward this end we have developed gene therapy with an adeno-associated virus (AAV) vector that expresses GAA specifically in the liver accompanied by GAA secretion and receptor-mediated uptake of GAA in the heart and skeletal muscle. It is the central hypothesis that continuous GAA production from a liver depot will surpass the benefits achieved with ERT in Pompe disease.
Osteoporosis is a large and Growing public health concern that affects over 20 million American and leads to 1.5 million fractures every year. While various drugs are approved to treat osteoporosis, no agent is fully able to restore skeletal health in most patients with severe disease. This proposal aims to extend a proof-of-principle clinical trial that evaluates short-term therapy with a novel combination of osteoporosis medications followed by a single dose of a longer-acting agent. This treatment regimen has the potential to significantly improve the management of patients with established osteoporosis.
Systemic sclerosis (SSc) is a multisystem autoimmune illness characterized by vasculopathy, immune system activation and fibrosis of the skin and internal organs. SSc affects approximately 240 people per million in the U.S. but is a disease for which there is no FDA approved medication. Current hypothesis of pathogenesis suggests that a vascular injury with endothelial dysfunction may be an inciting event contributing to immunologic activation and fibrosis in the pathogenesis of the disease. More than 90% of individuals with SSc have vascular complications including Raynaud phenomenon, digital ulcers or gangrene and pulmonary hypertension; with microvascular abnormalities felt to contribute to Raynaud and digital ulcerations.
Statin medications are well-recognized to have pleiotropic effects which may modify all three aspects of SSc pathogenesis. Early diagnosis and treatment of microvascular endothelial dysfunction and Raynaud phenomenon may have the greatest effect in early disease. Thus, this study hypothesizes that treatment with atorvastatin in a well-defined cohort of early diffuse systemic sclerosis will produce beneficial results.
A Double-blinded, Placebo-controlled Pilot Study of Dimethyl Fumarate (DMF) in Pulmonary Arterial Hypertension (PAH) Associated With Systemic Sclerosis (SSc-PAH): The Effect of DMF on Clinical Disease and Biomarkers of Oxidative Stress
Systemic sclerosis (SSc) is a complex, multifactorial autoimmune disease characterized by fibrosis and vasculopathy in skin and various internal organs such as the lungs, kidneys and heart disease with no specific treatment. Pulmonary arterial hypertension (PAH) is a common complication of SSc, and compared to other subgroups of PAH patients, responds poorly to currently approved vasodilators. Oxidative damage is a well-defined component of lung disease in SSc as well as in other organs and pathology studies have shown evidence of oxidative damage in SSc lungs. Dimethyl fumarate (DMF), recently been approved as a treatment for multiple sclerosis, triggers the general response to oxidative damage through Nrf2, resulting in the induction of multiple enzymes designed to counteract the oxidative process. Preclinical studies by the study team as well as other groups have shown that DMF inhibits PAH in murine models. In addition, multiple markers of oxidative stress are elevated in patients with SSc and SSc-PAH, suggesting that this is an important pathway mediating vascular damage in SSc-PAH. On the basis of these studies, the study team proposes a double-blinded, placebo-controlled study of DMF added to stable background, standard of care PAH therapy in SSc‐PAH patients, comparing the change in 6-minute walk distance (6MWD) at 24 weeks to baseline in DMF compared to placebo-treated patients.
Traumatic knee injury is common and highly debilitating. Surgical reconstruction/repair improves knee biomechanics and function, but neuromuscular dysfunction persists for years despite rehabilitation, hindering resumption of normal activities, increasing the risk of further injury and, in a majority of patients, hastening the development of knee osteoarthritis (OA). The period from the injury through the early, post-surgical period is critical for the development of functional deficits, as the trauma of the injury and surgery combine with muscle disuse to reduce skeletal muscle size and intrinsic function.
This study aims to evaluate the utility of neuromuscular electrical stimulation (NMES), initiated following injury and maintained through the early post-surgical period, to prevent muscle atrophy and intrinsic contractile dysfunction.