Atheroma Reduction With Chloroquine in Patients With the Metabolic Syndrome (ARCH-MS)

Inclusion Criteria

• Diagnosis of metabolic syndrome, as determined by at least three of the following five criteria:
• Elevated fasting triglyceride level greater than 150 mg/dL
• Low HDL cholesterol levels: less than 50 mg/dL for women and less than 40 mg/dL for men
• Hypertension (greater than or equal to 130/85 mm Hg and less than or equal to 160/100 mm Hg) untreated; or hypertension controlled (less than or equal to 150/90 mm Hg) on a stable medication regimen for 4 weeks prior to baseline visit.
• Increased waist circumference: greater than 35 inches in women and greater than 40 inches in men
• Elevated fasting glucose level greater than or equal to 100 mg/dL and less than or equal to 126 mg/dL
• Willing to use acceptable form of birth control
• Subjects may be on a stable doses of a statin drug for at least 3 months
• Subjects may be on a stable doses of L-thyroxine for at least 3 months

Exclusion Criteria

• Prior travel treatment with chloroquine or hydroxychloroquine as follows:
• Any exposure in the past 2 years
• More than 30 days of therapy if exposure was between 2 and 5 years ago
• More than 90 days of therapy if exposure was between 5 and 10 years ago
• More than 6 months of therapy if exposure was 10 to 20 years ago
• More than 1 year of therapy if exposure was 20 to 30 years ago
• No limit if last exposure was more than 30 years ago (e.g., during the Vietnam conflict)
• Morbid obesity (body mass index [BMI] greater than 45)
• Coronary artery disease or other vascular disease
• History of stroke
• Significant kidney disease (estimated glomerular filtration rate (eGFR)less than 60 mL/min/1.73 m2)
• Diabetes
• Seizure disorder
• History of psoriasis
• Blood disorders, including anemia (i.e., hemoglobin levels less than 13 g/dL in men and less than 12 g/dL in women)
• Current malignancy or active treatment for recurrence prevention, example tamoxifen. Cancer considered to be cured, either as a result of surgery or other treatment is not exclusionary.
• Asthma requiring daily beta agonist therapy or intermittent oral steroids is exclusionary. Inhaled steroids are acceptable. Obstructive sleep apnea will be allowed if Continuous Positive Airway Pressure (CPAP) or other therapy has been stable for 6 months. Other active respiratory diseases are excluded.
• Liver disease, or liver function test results greater than twice the normal value
• Active infection, including HIV
• Serious illness requiring ongoing medical care or medication
• Treatment with atypical anti-psychotic medication. Treatment with any other medication for psychiatric illness, unless on a stable dose for 6 weeks prior to enrollment. Patients with unstable psychiatric disorders are excluded per the decision of the study MD regardless of medication history.
• Receiving any of the following lipid lowering medications: niacin, fibrates, or fish oils greater than 1 gram
• Uncontrolled hypertension (blood pressure greater than or equal to 150/90) at baseline visit.
• Need for daily over the counter medications, or currently taking cimetidine or greater than 1000 IU vitamin E daily and unwilling to reduce or discontinue the use of vitamin E or discontinue cimetidine for the duration of the study. Patients taking greater than 1000 IU of vitamin E should reduce the dose 30 days prior to randomization.
• Pregnant, breastfeeding, or intending to become pregnant
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Retinal disease
• Auditory disease or hearing loss; patients with total, irreversible hearing loss can be enrolled
• Participation in another clinical trial within past 30 days prior to screening and 60 days prior to randomization. Questionnaire or observational studies are not exclusionary.