MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics

Not Applicable

Completed

• Conditions: Rheumatoid Arthritis; Healthy Controls
• Interventions: 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

• Registration Number: NCT04226131
• Lead Sponsor: Duke University

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 participants will undergo the following at Visit 1:

* Brief medical history including list of medications

* PROMIS Measures (If unable to complete online prior to Visit-1)

* Anthropometric Measurements: Height/Weight/Body Mass Index

* Vitals: Resting Blood Pressure and Heart Rate

* Fasting Blood Draw

* Physician RA Joint Assessment: Disease Activity (DAS-28) Assessment

* MyotonPro Skeletal Muscle Biomechanical Assessments

* NIRS Muscle Oxidative Capacity Test

* Muscle Biopsy

Brief Medical History and Medication Review: A brief medical history including list of medications will be performed by study staff.

Questionnaires: Using Duke's REDCap (Research Electronic Data Capture) interface, a battery of Patient-Reported Outcomes Measurement Information System (PROMIS) self-reported health outcome measures has been added to a computerized interface and will be associated with this investigation. Measures include global health, pain, fatigue, physical function, self-efficacy for disease management and sleep. Of note, staff testing of this battery indicated this could be completed between 10 and 12 minutes; the investigators project participants may take longer, expecting approximately 30 minutes. Except for global health, scoring is performed by the computerized REDCap interface. Specific measure names and versions as listed in REDCap are listed below:

* PROMIS SF v1.1 Global Health

* PROMIS SF v2.0 Physical Function 20a

* PROMIS Scale v1.0 Pain Intensity 3a

* PROMIS SF v1.0 General Life Satisfaction 5a

* PROMIS Bank v1.0 Short Form Fatigue 8a

* Stanford Brief Activity Survey

Study participants will undergo the following at Visit 2:

* BodPod and Minimal Waist Circumference

* Strength Tests

* Isometric Leg Extension Machine - Quadriceps / Hamstrings Strength

* Hand Dynamometer - Grip Strength

* Cardiopulmonary Exercise Test

Study Timeline

• Study First Submitted: 2020-01-09
• Study First Submitted QC: 2020-01-09
• Study First Posted: 2020-01-13
• Study Start: 2020-09-09
• Status Verified: 2023-07
• Primary Completion: 2023-07-07
• Study Completion: 2023-07-07
• Last Update Submitted: 2023-07-12
• Last Update Posted: 2023-07-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early Rheumatoid Arthritis (RA)	Disease Activity (DAS-28) Assessment	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
Early Rheumatoid Arthritis (RA)	Questionnaires	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
Early Rheumatoid Arthritis (RA)	Skeletal Muscle Biomechanical Property Assessment	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
Early Rheumatoid Arthritis (RA)	Skeletal Muscle Mitochondrial Respiratory Capacity	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
Early Rheumatoid Arthritis (RA)	Blood Draw	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
Early Rheumatoid Arthritis (RA)	Body Composition	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
Age-, Sex-, BMI-matched Healthy Controls	Blood Draw	Healthy Controls.
Age-, Sex-, BMI-matched Healthy Controls	Muscle Biopsy	Healthy Controls.
Early Rheumatoid Arthritis (RA)	Muscle Biopsy	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
Early Rheumatoid Arthritis (RA)	Cardiopulmonary Exercise Test (CPET)	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
Early Rheumatoid Arthritis (RA)	Strength Testing	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
Age-, Sex-, BMI-matched Healthy Controls	Body Composition	Healthy Controls.
Age-, Sex-, BMI-matched Healthy Controls	Strength Testing	Healthy Controls.
Age-, Sex-, BMI-matched Healthy Controls	Questionnaires	Healthy Controls.
Age-, Sex-, BMI-matched Healthy Controls	Skeletal Muscle Mitochondrial Respiratory Capacity	Healthy Controls.
Age-, Sex-, BMI-matched Healthy Controls	Skeletal Muscle Biomechanical Property Assessment	Healthy Controls.
Age-, Sex-, BMI-matched Healthy Controls	Cardiopulmonary Exercise Test (CPET)	Healthy Controls.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Myobundle function	Baseline	Determine whether myobundle function, including force production and tissue stiffness (kPa), in RA differs compared to controls.
Janus kinase/signal transducers and activators of transcription 3 pathway (JAK/STAT3) signaling in skeletal muscle	Baseline	Determine whether JAK/STAT3 signaling is upregulated in RA skeletal muscle compared to controls.

Trial Locations

Locations (1)

Duke Center for Living; 🇺🇸 Durham, North Carolina, United States