Clinical Trials in the Spotlight Main Page

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports a range of clinical trials studying new and existing interventions for prevention and treatment of arthritis, musculoskeletal, and skin diseases.  Investigators supported by the NIAMS need your help finding individuals to participate in clinical trials.  Participating in clinical trials allows you to play an active role as a volunteer in research and contribute to generating new knowledge about the disease/condition, and potentially future treatments.  The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible. 

Study Description

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.

In order to test these hypotheses, the study team will establish a cohort of well-characterized RA subjects and non-RA controls, who will undergo assessment of physical function, body composition, disease activity, and needle biopsy from the vastus lateralis muscle (aim 1). In aim 2, the study team will conduct a 12-week, double-blind, and placebo-controlled study with pioglitazone in patients with RA who are insulin resistant to determine whether treatment of insulin resistance will improve functional characteristics, cellular and molecular responses in their skeletal muscle. Completion of the proposed research will begin to define the molecular underpinnings of impaired skeletal muscle homeostasis in RA.

ELIGIBILITY CRITERIA:

Ages Eligible for Study:           35 Years to 65 Years   (Adult, Older Adult)

Sexes Eligible for Study:          All

Accepts Healthy Volunteers:  Yes

Inclusion Criteria:

Inclusion Criteria for RA patients (cross-sectional study):

  • Age 35-65
  • Diagnosed with RA by a Rheumatologist and according to American College of Rheumatology 2010 criteria

Inclusion Criteria for controls (cross-sectional study):

  • Age 35-65
  • In generally good health

Inclusion Criteria for RA patients who are: (i) insulin resistant by the 2-hour glucose tolerance test; (ii) have the presence of 3 or more risk factors for metabolic syndrome (MetS) according to the ATP III Clinical Identification of MetS criteria; (iii) have a Hemoglobin A1c level equal or greater than 5.7 and less than 6.5.

  • Age 35-65
  • Diagnosed with RA by a Rheumatologist and according to American College of Rheumatology 2010 criteria
  • Insulin resistant according to the Matsuda index

Exclusion Criteria:

Exclusion Criteria (cross-sectional study):

  • Age <35 or >65
  • Pregnant, breast-feeding, cognitive dysfunction, incarcerated or otherwise vulnerable persons
  • Any acute or chronic medical or psychiatric disorder that, in the opinion of the investigators, would impair evaluation of the study measures

Exclusion criteria (pioglitazone randomized clinical trial):

  • Women of reproductive age who are pregnant or who do not agree to effective birth control or who are lactating
  • Clinically significant hepatic, cardiac or renal impairment
  • Untreated osteoporosis
  • Active cancer other than skin cancer
  • Use of drugs (other than glucocorticoids) or nutritional supplements known to affect skeletal muscle mass
  • Participation in regular and intense physical training
  • Severe edema.

Exclusion criteria for the muscle biopsy (cross-sectional and pioglitazone randomized clinical trial):

  • Bleeding diathesis or chronic anticoagulant therapy
  • Unable or unwilling to discontinue aspirin or non-steroidal anti-inflammatory drugs for 5 days prior to muscle biopsy

Study Design:

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Double (Participant, Investigator)

Primary Purpose: Treatment

Study Location(s):

University of Alabama at Birmingham, Birmingham, Alabama, United States, 35294

Study Website:

https://clinicaltrials.gov/ct2/show/NCT02535832?term=NCT02535832&rank=1

Last Reviewed: 05/06/2019