MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics (MusculRA)
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ClinicalTrials.gov Identifier: NCT04226131 |
Recruitment Status :
Completed
First Posted : January 13, 2020
Last Update Posted : July 13, 2023
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Condition or disease | Intervention/treatment | Phase |
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Rheumatoid Arthritis Healthy Controls | 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 | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 21 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | 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 |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics |
Actual Study Start Date : | September 9, 2020 |
Actual Primary Completion Date : | July 7, 2023 |
Actual Study Completion Date : | July 7, 2023 |
Arm | Intervention/treatment |
---|---|
Early Rheumatoid Arthritis (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 Disease-modifying anti-rheumatic drugs (bDMARD) therapy
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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 Name: Near-Infrared Spectroscopy (NIRS) 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.
Other Name: Myotonometry |
Age-, Sex-, BMI-matched Healthy Controls
Healthy Controls.
|
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: 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 Name: Near-Infrared Spectroscopy (NIRS) 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.
Other Name: Myotonometry |
- 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.
- Myobundle function [ Time Frame: 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 [ Time Frame: Baseline ]Determine whether JAK/STAT3 signaling is upregulated in RA skeletal muscle compared to controls.
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Ages Eligible for Study: | 25 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04226131
United States, North Carolina | |
Duke Center for Living | |
Durham, North Carolina, United States, 27705 |
Principal Investigator: | Kim M Huffman, MD | Duke University |
Responsible Party: | Duke University |
ClinicalTrials.gov Identifier: | NCT04226131 |
Other Study ID Numbers: |
Pro00103552 |
First Posted: | January 13, 2020 Key Record Dates |
Last Update Posted: | July 13, 2023 |
Last Verified: | July 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Skeletal Muscle |
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases |
Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |