MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Duke University
- Enrollment
- 21
- Locations
- 2
- Primary Endpoint
- Muscle stiffness and elasticity
Study Overview
Brief Summary
Persons with rheumatoid arthritis (RA) suffer from increased disability and mortality, in part resulting from skeletal muscle impairments. In this study, our objective is to determine if skeletal muscle biomechanical properties are altered in RA. Up to 15 participants with early RA defined as duration of disease/symptoms of less than 6 months (where "duration" denotes the length of time the patient has had symptoms/disease, not the length of time since RA diagnosis) AND prior to starting biologic Disease-modifying anti-rheumatic drugs (bDMARD) therapy and 15 age-, sex-, and BMI-matched controls will undergo clinical assessments of skeletal muscle stiffness and elasticity as measured by the hand-held MyotonPro device. Additional study participant assessments include cardiopulmonary exercise testing, muscle strength testing, body composition measurement using BodPod, muscle oxidative capacity testing using near-infrared spectroscopy, and thigh muscle needle biopsies to compare clinical findings to an ex vivo cultured myobundle system. Primary statistical analyses will be comparisons of skeletal muscle parameters in RA compared to controls and correlations to determine relationships between variables. Thigh muscle biopsies are a low-risk procedure that may cause minor local soreness and bleeding; all other clinical assessments are non-invasive and will induce minimal discomfort to participants.
Detailed Description
Study design: Up to 30 adults, 25-75 yrs. of age may be recruited and enrolled to participate in a cross-sectional study. Subjects will be divided between two cohorts: 1) persons with early RA (n=15) and 2) age-, sex-, Body Mass Index (BMI)-matched healthy controls (n=15). The goal is to have equal numbers between groups complete the study. Early RA defined as duration of disease/symptoms of less than 6 months (where "duration" denotes the length of time the patient has had symptoms/disease, not the length of time since RA diagnosis) AND prior to starting biologic DMARD therapy were chosen to minimize the effect of medications on skeletal muscle.
Demographics and comorbidities will be assessed via self-report during an initial phone screening interview, with confirmation from the computerized medical record. Once it has been determined that the subject meets pre-screening criteria, they will be scheduled for Visit-1.
Phone Pre-Screening: Demographics and comorbidities will be assessed via self-report during an initial phone screening interview, with confirmation from the electronic medical record. Once it has been determined that the subject meets pre-screening criteria, they will be scheduled for a virtual study information/consent session.
Online surveys: After completion of the e-consent process, participants will be provided a REDCap survey link via email to complete some online questionnaires about their overall health, pain, fatigue, physical function, sleep and ability to manage their disease.
The study involves two on-site study visits at the Duke Center for Living; each visit lasts approximately 2.5 hours.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 25 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Study participants will include 25-75 year-old adults with early rheumatoid arthritis and healthy age-, gender-, and BMI-matched controls.
- •Rheumatoid arthritis participants will all be seropositive (positive rheumatoid factor or anti-citrullinated protein antibody) or with erosions typical of RA on radiographs.
- •Meet 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for RA.
- •Early RA defined as duration of disease/symptoms of less than 6 months (where "duration" denotes the length of time the patient has had symptoms/disease, not the length of time since RA diagnosis) AND prior to starting biologic DMARD therapy.
- •Participants will not be engaging in regular exercise (According to 2018 US guidelines): not more than 150 minutes per week of moderate intensity exercise or 75 minutes per week of vigorous intensity exercise) for at least three months prior to consent.
Exclusion Criteria
- •Early RA participants will be excluded if they have already started bDMARD therapy.
- •The investigators will exclude persons using non-aspirin anticoagulants that would complicate the biopsy. There will be a wash-out period of seven days for anti-platelet agents, and three days for NSAIDs prior to biopsies.
- •Uncontrolled thyroid diseases
- •Chronic obstructive lung disease
- •Parkinson's disease
- •Ankylosing spondylitis
- •Congestive Heart Failure Class III and above will be excluded based on recognized effects on skeletal muscle.
- •Patients with absolute or relative contraindications to exercise will be excluded: recent (<6 months) acute cardiac event, unstable angina, uncontrolled dysrhythmias causing symptoms or hemodynamic compromise, symptomatic aortic stenosis, uncontrolled symptomatic heart failure, acute pulmonary embolus, acute myocarditis or pericarditis, suspected or known dissecting aneurism or acute systemic infection, left main coronary stenosis, moderate stenotic valvular heart disease, outflow tract obstruction, high degree atrioventricular (AV) block, ventricular aneurysm.
- •Uncontrolled metabolic disease (e.g. diabetes, thyrotoxicosis, myxoedema)
- •Uncontrolled pulmonary disease (e.g. severe COPD or pulmonary fibrosis)
- •Mental or physical impairment leading to inability to exercise adequately
- •Pregnant women will be excluded as determined via menstrual history/self-reporting.
Outcomes
Primary Outcomes
Muscle stiffness and elasticity
Time Frame: Baseline
Determine whether passive skeletal muscle stiffness (Newtons/meters) and elasticity (logarithmic decrement) are different in RA compared to matched healthy controls.
Secondary Outcomes
- Myobundle function(Baseline)
- Janus kinase/signal transducers and activators of transcription 3 pathway (JAK/STAT3) signaling in skeletal muscle(Baseline)