Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis
Condition: Rheumatoid Arthritis; Insulin Resistance
MeSH terms: Arthritis; Arthritis, Rheumatoid; Insulin Resistance
Intervention: Hydroxychloroquine
Intervention description: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
Intervention MeSH terms: Hydroxychloroquine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: rheumatoid arthritis; insulin resistance; hydroxychloroquine; cholesterol

Summary:

      The purpose of this study is to determine whether hydroxychloroquine (HCQ) reduces insulin
      resistance in non-diabetic subjects with rheumatoid arthritis (RA). The investigators will
      conduct a double-blind randomized crossover trial in subjects with RA to test the hypothesis
      that HCQ improves insulin sensitivity. The investigators will also use data from the trial to
      identify determinants of insulin resistance in RA. The investigators hypothesize that RA will
      be associated with an increased risk of insulin resistance and that independent risk factors
      for increased insulin resistance in RA include higher BMI, elevated acute phase reactants,
      greater fat to muscle ratio, and less physical activity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 or older

          -  Able to provide informed consent and comply with study visits

          -  Hemoglobin ≥ 10 g/dL (within last two months)

          -  WBC ≥ 4 K/uL (within last two months)

          -  Platelet count ≥ 150 ≤ 450 K/uL (within last two months)

          -  (GFR) Creatinine clearance ≥ 70 ml/min (MDRD) (within last two months)

          -  SGOT, SGPT ≤ 1.5 times upper limits of normal (within last two months)

          -  Normal eye exam within 12 months of study entry (copy of letter from subject's
             ophthalmologist or optometrist stating that the subject has no evidence of macular
             pathology)

          -  Diagnosis of rheumatoid arthritis

        Exclusion Criteria:

          -  History of any neuromuscular disease including muscular dystrophy, metabolic
             myopathies, peripheral neuropathy, multiple sclerosis, and other myopathies or
             myositides

          -  History of diabetes or fasting plasma glucose of 126 mg/dl or greater

          -  History of any untoward reaction to antimalarials

          -  Uncontrolled hypertension (>140/90)

          -  History of any ophthalmologic disease except for glaucoma or cataracts

          -  Planned elective surgery during the study period

          -  Digoxin therapy

          -  Treatment with corticosteroids (> 5 mg) for any disorder

          -  History of psoriasis

          -  Any chronic disease that in the opinion of the investigator warrants exclusion (e.g.
             inflammatory bowel disease, malignancy other than basal cell carcinoma, chronic liver
             disease)

          -  History of chronic intestinal disorders (Crohn's disease, ulcerative colitis, celiac
             sprue, collagenous colitis, eosinophilic enteritis)

          -  Creatinine clearance ≤ 60 ml/min (MDRD) (within last two months)

          -  Hemoglobin ≤ 10 g/dL (within last two months)

          -  WBC ≤ 4 K/uL (within last two months)

          -  Platelet count ≤ 150 ≥ 450 K/uL (within last two months)

          -  SGOT, SGPT ≥ 1.5 times upper limits of normal (within last two months)

          -  Women who are pregnant or breastfeeding