Genotoxic Stress, Atherosclerosis, and Metabolic Syndrome-AIM 2
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Metabolic Syndrome X
- Sponsor
- Washington University School of Medicine
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Insulin Sensitivity
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of metabolic syndrome, as determined by at least three of the following five criteria:
- •Elevated fasting triglyceride levels greater than or equal to 150 mg/dL
- •Low HDL cholesterol levels: less than 50 mg/dL for women and less than 40 mg/dL for men
- •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.
- •Increased waist circumference: greater than 35 inches in women and greater than 40 inches in men
- •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:
- •any exposure in the past 2 years,
- •\>30 days of therapy if exposure was between 2 and 5 years ago,
- •\>90 days of therapy if exposure was between 5 and 10 years ago,
- •\>6 months of therapy if exposure was 10 to 20 years ago,
- •\>1 year of therapy if exposure was 20 to 30 years ago,
- •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
Outcomes
Primary Outcomes
Insulin Sensitivity
Time Frame: assessed every 8 - 10 weeks at the end of each treatment period
Hepatic insulin sensitivity was measured by comparing glucose production at baseline of zero insulin infusion rate with glucose production at 56 pmol/m2/min. Hepatic insulin sensitivity was expressed as the percent suppression, such that greater percent suppression indicated greater hepatic insulin sensitivity. There are no reference values, since the patients served as their own controls.
Secondary Outcomes
- Diastolic Blood Pressure(Assessed every 8-10 weeks at the end of each treatment period.)
- Non-HDL Cholesterol(Assessed every 8-10 weeks at the end of each treatment period.)
- Systolic Blood Pressure(Assessed every 8-10 weeks at the end of each treatment period)
- Triglycerides(Assessed every 8-10 weeks at the end of each treatment period.)
- Total Cholesterol(Assessed every 8-10 weeks at the end of each treatment period.)
- Low-density Lipoprotein(Assessed every 8-10 weeks at the end of each treatment period.)