MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics

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

Interventions

OTHER

Blood Draw

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.

OTHER

Disease Activity (DAS-28) Assessment

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.

OTHER

Skeletal Muscle Mitochondrial Respiratory Capacity

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.

OTHER

Muscle Biopsy

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.

OTHER

Body Composition

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

OTHER

Cardiopulmonary Exercise Test (CPET)

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.

OTHER

Strength Testing

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

OTHER

Questionnaires

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

OTHER

Skeletal Muscle Biomechanical Property Assessment

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.

Sponsors & Collaborators

• Gilead Sciences

  collaborator INDUSTRY

• Duke University

  lead OTHER

Principal Investigators

• Kim M Huffman, MD · Duke University

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-09-09

Primary Completion

2023-07-07

Completion

2023-07-07

Countries

• United States

Study Locations