MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics
Condition: Rheumatoid Arthritis; Healthy Controls
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional

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
    

Intervention name(s): Blood Draw; Disease Activity (DAS-28) Assessment; Skeletal Muscle Mitochondrial Respiratory Capacity; Muscle Biopsy; Body Composition; Cardiopulmonary Exercise Test (CPET); Strength Testing; Questionnaires; Skeletal Muscle Biomechanical Property Assessment
Intervention type(s): Other; Other; Other; Other; Other; Other; Other; Other; Other
Intervention description(s): 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.; 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.; 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.; 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.; Body composition assessments include circumference measurements and the BOD POD®. Minimal waist circumference measurements will be taken using a tape measure.; 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.; Strength assessments will include dynamometry-assessed grip and quadriceps strength (Cybex HUMAC NORM, Comp Sports Med, Inc., Stoughton, MA) tests; Measures include global health, pain, fatigue, physical function, self-efficacy for disease management and sleep.; 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 intervention name(s): Near-Infrared Spectroscopy (NIRS); Myotonometry
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
Keywords: Skeletal Muscle