Chloroquine to Treat People With Metabolic Syndrome Aim2 (ARCH-MS)
Condition: Metabolic Syndrome X; Overweight; Hypertension; Dyslipidemias; Prediabetic State
MeSH terms: Overweight; Metabolic Syndrome; Dyslipidemias; Prediabetic State; Syndrome
Intervention: Placebo Comparator: First Intervention (3 weeks); Active Comparator: Second Intervention (3 weeks); Active Comparator: Third Intervention (3 weeks); Active Comparator: Fourth Intervention (3 weeks)
Intervention description: once daily placebo tablet for 3 weeks followed by: euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells; Once daily 80mg chloroquine or placebo tablet 3 Weeks followed by euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells; Once daily 80mg tablet for 3 weeks followed by: euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells; Once daily 250mg tablet for 3 weeks followed by: euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells
Intervention MeSH terms: Chloroquine; Chloroquine diphosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Insulin Resistance; Atherosclerosis; Metabolic Syndrome

Summary:

      Metabolic syndrome consists of a group of co-occuring conditions that increase an
      individual's risk of developing heart disease, stroke, and diabetes. The purpose of this
      study is to evaluate the short-term effectiveness of chloroquine, a protein-activation
      medication, at improving metabolic syndrome.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of metabolic syndrome, as determined by at least three of the following five
             criteria:

               1. Elevated fasting triglyceride levels greater than or equal to 150 mg/dL

               2. Low HDL cholesterol levels: less than 50 mg/dL for women and less than 40 mg/dL
                  for men

               3. Hypertension (=>130/85 mm Hg =<160/100 mm Hg) untreated; or hypertension
                  controlled (=<150/90 mm Hg) on a stable medication regimen for 4 weeks prior to
                  baseline visit.

               4. Increased waist circumference: greater than 35 inches in women and greater than
                  40 inches in men

               5. Elevated fasting glucose levels =<100 mg/dL but =>126 mg/dL

          -  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

          -  Willing to use acceptable form of birth control (e.g., hormonal birth control, double
             barrier methods)

        Exclusion Criteria:

          -  Prior travel treatment with chloroquine or hydroxychloroquine as follows:

               1. any exposure in the past 2 years,

               2. >30 days of therapy if exposure was between 2 and 5 years ago,

               3. >90 days of therapy if exposure was between 5 and 10 years ago,

               4. >6 months of therapy if exposure was 10 to 20 years ago,

               5. >1 year of therapy if exposure was 20 to 30 years ago,

               6. No limit if last exposure was >30 years ago, ex. during the Vietnam conflict.

          -  Morbid obesity (body mass index [BMI] greater than 45)

          -  Coronary artery disease or other vascular disease

          -  History of stroke

          -  Chronic kidney insufficiency (i.e.,estimated glomerular filtration rate (eGFR) less
             than 60 ml/min/1.73m2)

          -  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.

          -  Taking any of the following lipid lowering medications: niacin, fibrates, and greater
             than 1 gm fish oils

          -  Uncontrolled hypertension (BP >150/90) at enrollment.

          -  Need for daily over the counter medications, or currently taking cimetidine or >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. Persons taking >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 (in particular, drusen or pigmentary changes at the macula); any
             ocular disease that interferes with the eye examination (e.g., cataracts)

          -  Auditory disease or hearing loss; persons 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.