MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics

NCT04226131 | Completed

• 1 other identifier: Pro00103552
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis; Healthy Controls

Keywords

Skeletal Muscle

Outcome Measures

Primary Outcomes (1)

• Muscle stiffness and elasticity

  Determine whether passive skeletal muscle stiffness (Newtons/meters) and elasticity (logarithmic decrement) are different in RA compared to matched healthy controls.

  Baseline

Secondary Outcomes (2)

• Myobundle function

  Baseline

• Janus kinase/signal transducers and activators of transcription 3 pathway (JAK/STAT3) signaling in skeletal muscle

  Baseline

Study Arms (2)

Early Rheumatoid Arthritis (RA)

OTHER

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

Other: Blood Draw; Other: Disease Activity (DAS-28) Assessment; Other: Skeletal Muscle Mitochondrial Respiratory Capacity; Other: Muscle Biopsy; Other: Body Composition; Other: Cardiopulmonary Exercise Test (CPET); Other: Strength Testing; Other: Questionnaires; Other: Skeletal Muscle Biomechanical Property Assessment

Age-, Sex-, BMI-matched Healthy Controls

OTHER

Healthy Controls.

Other: Blood Draw; Other: Skeletal Muscle Mitochondrial Respiratory Capacity; Other: Muscle Biopsy; Other: Body Composition; Other: Cardiopulmonary Exercise Test (CPET); Other: Strength Testing; Other: Questionnaires; Other: Skeletal Muscle Biomechanical Property Assessment

Interventions

Blood Draw OTHER

A study nurse will draw up to 150 mL of blood to measure erythrocyte sedimentation rate (ESR) and measures of immune cell function. ESR is a common hematology test that is a measure of inflammation.

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Disease Activity (DAS-28) Assessment OTHER

Participants in the RA cohort will receive a 28-joint examination by the study physician to assess RA disease activity and report their overall health assessment.

Early Rheumatoid Arthritis (RA)

Skeletal Muscle Mitochondrial Respiratory Capacity OTHER

Near-Infrared Spectroscopy (NIRS) will be used to measure oxidative capacity of forearm flexor digitorum profundus and medial gastrocnemius muscles using the PortaMon device (Artinis Medical Systems, The Netherlands). NIRS is a low-cost, non-invasive method that estimates muscle oxidative capacity by measuring oxygen consumption (mVO2) recovery kinetics via assessment of intramuscular oxy- and deoxy-hemoglobin concentration following a sequence of brief, rapid arterial cuff occlusions. NIRS measures mitochondrial oxidative function as the mVO2 recovery rate constant k. In the absence of blood flow, changes in muscle oxygenation occur via oxygen consumption alone. In persons without RA, this non-invasive approach is highly correlated with muscle respiratory capacity assessed via muscle biopsies using in situ permiabilized fiber bundles and the Oroboros O2k system.

Also known as: Near-Infrared Spectroscopy (NIRS)

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Muscle Biopsy OTHER

After local anesthesia (xylocaine, 2%) is injected, a small incision will be made in the thigh. Four to six small pieces of muscle about the size of a pea will be surgically removed. The incision site will be closed using steri-strips and/or derma-bond, and a light dressing applied.

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Body Composition OTHER

Body composition assessments include circumference measurements and the BOD POD®. Minimal waist circumference measurements will be taken using a tape measure.

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Cardiopulmonary Exercise Test (CPET) OTHER

Cardiorespiratory aerobic capacity (VO2 peak), will be assessed using a maximal treadmill test protocol with cardiopulmonary gas exchange. Subjects will be asked to exercise on a treadmill to their perceived maximum ability and effort during which time they will have a mouthpiece in their mouth to determine maximal oxygen use/consumption through breathing. For safety purposes the subject will be monitored by electrocardiogram (ECG) and their blood pressure will be measured at rest and throughout the exercise phase of this test.

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Strength Testing OTHER

Strength assessments will include dynamometry-assessed grip and quadriceps strength (Cybex HUMAC NORM, Comp Sports Med, Inc., Stoughton, MA) tests

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Questionnaires OTHER

Measures include global health, pain, fatigue, physical function, self-efficacy for disease management and sleep.

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Skeletal Muscle Biomechanical Property Assessment OTHER

Passive skeletal muscle stiffness and elasticity measurements of bilateral biceps brachii, flexor carpi radialis, vastus lateralis, and tibialis anterior using mechanical deformation with myotonometry using the MyotonPro device.

Also known as: Myotonometry

Age-, Sex-, BMI-matched Healthy Controls; Early Rheumatoid Arthritis (RA)

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• Gilead Sciences: collaborator

Study Sites (1)

Duke Center for Living

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Blood Specimen Collection; Restraint, Physical; Spectroscopy, Near-Infrared; Body Composition; Exercise Test; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Behavior Control; Therapeutics; Immobilization; Diagnostic Imaging; Spectrum Analysis; Chemistry Techniques, Analytical; Biochemical Phenomena; Chemical Phenomena; Metabolism; Body Constitution; Physiological Phenomena; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Kim M Huffman, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 DMARD therapy and 15 age-, sex-, and BMI-matched controls

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 13, 2020
• Study Start: September 9, 2020
• Primary Completion: July 7, 2023
• Study Completion: July 7, 2023
• Last Updated: July 13, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)