Clinical trial NCT00455325
Conditions: Metabolic Syndrome X Overweight Hypertension Dyslipidemias Prediabetic State
Keywords: Insulin Resistance Atherosclerosis Metabolic Syndrome
Sponsor: Washington University School of Medicine
Start date: 2004-09-01; Completion date: 2012-03-01
Enrollment: 35 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief 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.

Detailed description:
Metabolic syndrome is one of the most common disorders in industrialized countries. It consists of abnormal serum lipids, glucose intolerance, elevated blood pressure, and central obesity in the setting of insulin resistance. The syndrome substantially increases the risk of developing diabetes and vascular disease, but there is no clear unifying approach to treat this disorder. In animals, activation of the protein ataxia telangiectasia mutated (ATM) using the antimalarial drug chloroquine improves features of metabolic syndrome and decreases atherosclerosis, a build-up of fatty plaque within arteries. The purpose of this study is to evaluate the effectiveness of short-term treatment with low doses of chloroquine as a way of managing metabolic syndrome.

Participants in this study will initially receive placebo for 3 weeks, followed by increasing doses of chloroquine in three, 3-week intervals. Following each 3-week treatment, participants will be admitted to the research center for one day. There will be a period of no active treatment for 5 to 7 weeks following each admission to the research center to allow recovery from the blood drawing of the clamp procedure before the start of the next treatment interval.

Arms: arm 1: Cohort 1: Chloroquine placebo one tablet daily for 3 weeks, followed by 5-7 week rest period. arm 2: Cohort 2: 80mg chloroquine or placebo tablet once daily for Weeks 3, followed by 5-7 week rest period. arm 3: Cohort 3: 80mg chloroquine tablet daily: for 3 weeks, followed by 5-7 week rest period. arm 4: Cohort 4: 250mg chloroquine tablet daily: for 3 weeks, followed by 5-7 week rest period.
Interventions: intervention 1: Placebo Comparator: First Intervention (3 weeks) intervention 2: Active Comparator: Second Intervention (3 weeks) intervention 3: Active Comparator: Third Intervention (3 weeks) intervention 4: Active Comparator: Fourth Intervention (3 weeks)
Intervention descriptions: intervention 1: 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 intervention 2: 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 intervention 3: 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 intervention 4: 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

Protocol documents: