Official Title: “Genotoxic Stress, Atherosclerosis, and Metabolic Syndrome- Aim 3”

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 long-term effectiveness of chloroquine, a protein-activation medication, at reducing the progression of atherosclerosis in patients with the metabolic syndrome.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

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 examine the effect of long-term treatment with low doses of chloroquine on atherosclerosis in people with metabolic syndrome.

At a baseline study visit, participants will undergo an ultrasound of the neck to evaluate carotid artery intima-media thickness (IMT) and MRI to evaluate plaque composition. In addition, blood will be collected for laboratory testing and blood pressure will be measured.

Participants will then be randomly assigned to receive either placebo or chloroquine. Study visits will occur every 3 months for 1 year. At each visit, blood pressure will be measured and blood will be collected. At Months 6 and 12, a repeat ultrasound will be performed.

Participants will attend one follow-up visit at Month 24 and will undergo a final ultrasound and carotid MRI.

Intervention(s) in this Clinical Trial

• Drug: Chloroquine
  • One tablet of 80 mg of chloroquine on a daily basis for 12 months followed by 12 months off drug with 1 visit at month 12
• Drug: Chloroquine Placebo
  • Chloroquine Placebo tablet daily for 12 months followed by 12 months off drug with 1 visit at month 12

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants will receive 80 mg of chloroquine on a daily basis
• Placebo Comparator: 2
  • Participants will receive a placebo tablet on a daily basis

Primary Measures

• Carotid intima-media thickness
  • Time Frame: Measured at 6 months and 1 year
    Safety Issue?: No
• Plaque area and composition
  • Time Frame: Measured at 1 year
    Safety Issue?: No

Secondary Measures

• Blood pressure
  • Time Frame: Measured at 1 year
    Safety Issue?: No
• Glucose levels
  • Time Frame: Measured at 1 year
    Safety Issue?: No
• Change in lipid levels
  • Time Frame: Measured at 1 year
    Safety Issue?: No
• Monocyte activation
  • Time Frame: Measured at 1 year
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of metabolic syndrome, as determined by at least three of the following five criteria:
• 1. Elevated fasting triglyceride level >150 mg/dL
• 2. Low HDL cholesterol levels: < 50 mg/dL for women and <40 mg/dL for men
• 3. Blood pressure levels greater than 130/85 mm Hg but less than 160/100 if untreated, or taking up to three (3) antihypertensive medications with BP <140/90 mmHg
• 4. Increased waist circumference: greater than 35 inches in women and greater than 40 inches in men
• 5. Elevated fasting glucose level between 100 mg/dL and 126 mg/dL
• Willing to use acceptable form of birth control

Exclusion Criteria:

• Prior treatment with chloroquine or hydroxychloroquine
• 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/1.73m2)
• 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 cancer
• Asthma or active respiratory disease
• 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
• Mental illness requiring medication
• Receiving any of the following lipid lowering medications: niacin, fibrates, fish oils
• > 1 gram
• Blood pressure level greater than 140/90 mm Hg at study entry
• Need for daily over-the-counter medications
• Currently taking cimetidine or vitamin E
• Pregnant, breastfeeding, or intending to become pregnant
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Retinal disease
• Auditory disease or hearing loss
• Participation in another clinical trial in the 90 days prior to study entry

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

Clay F. Semenkovich, MD Principal Investigator Washington University School of Medicine  

Overall Contact: Janet B. McGill, MD 314-362-8688 jmcgill@im.wustl.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00455403

Study ID Number: 482

ClinicalTrials.gov Identifier: NCT00455403

Health Authority: United States: Federal Government

Click here for the Washington University Volunteer for Health Web site.

Click here for the Washington University Diabetes Research and Training Center Web site.

Click here for the Principal Investigator's Web site.