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| Sponsors and Collaborators: |
National Heart, Lung, and Blood Institute (NHLBI) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Washington University School of Medicine Singulex, Inc. |
|---|---|
| Information provided by: | National Heart, Lung, and Blood Institute (NHLBI) |
| ClinicalTrials.gov Identifier: | NCT00455403 |
Purpose
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.
Sub-study: VEGF and Cardiometabolic Risk, The purpose is to determine if the association of VEGF with atherosclerosis indicates that it should be a marker of the disorder.
| Condition | Intervention |
|---|---|
|
Metabolic Syndrome X Overweight Hypertension Dyslipidemias Prediabetic State |
Drug: Chloroquine Drug: Chloroquine Placebo |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | Genotoxic Stress, Atherosclerosis, and Metabolic Syndrome- Aim 3 |
| Estimated Enrollment: | 150 |
| Study Start Date: | April 2006 |
| Estimated Study Completion Date: | December 2011 |
| Estimated Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Experimental
Participants will receive 80 mg of chloroquine on a daily basis.
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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 24
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2: Placebo Comparator
Participants will receive a placebo tablet on a daily basis.
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Drug: Chloroquine Placebo
Chloroquine Placebo tablet daily for 12 months followed by 12 months off drug with 1 visit at month 24
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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. At month 12 a repeat carotid MRI is performed. Participants will attend one follow-up visit at Month 24 and will undergo a final ultrasound.
Sub-Study: VEGF and Cardiometabolic Risk, (This is an observational, case-study of existing baseline plasma and carotid intimal-medial thickness measurements) VEGF is also closely linked to vascular disease. From cell culture and animal models it is known that VEGF is increased in atherosclerotic lesions. It is controversial whether that relationship is causative or reparative.
Both pro- and anti-VEGF therapies have been proposed for atherosclerosis. However, the association of VEGF with atherosclerosis indicates that it should be a marker of the disorder, which is the hypothesis we wish to test.
No previous studies of circulating VEGF have been published.
Other markers may be related to vascular disease or VEGF in this dataset. TNF-alpha results in increased expression of VEGF and may be correlated positively with VEGF. By Erenna testing, cardiac troponin I can be measured at levels much lower than current clinical assays and is expected to be elevated in ischemia but not necessarily in the stable vascular disease anticipated in our subjects. hsCRP has been proposed as a marker for vascular disease that merits drug treatment in its own right and may also be correlated with VEGF and vascular disease. However, currently the relationship between hsCRP and vascular disease is not completely clear.
For this preliminary VEGF study observational data from the baseline only will be studied. Baseline testing includes carotid artery intimal-medial thickness, carotid MRI, lipid panel, complete blood count, comprehensive metabolic chemistry panel, TSH and glucose tolerance test with plasma insulin and glucose responses. Plasma collected at baseline (approximately 1 ml) will be transferred to Singulex on dry ice. Samples will be coded but will not contain patient identifiers. Erenna assays will be done for VEGF-A, cardiac troponin I,TNF-alpha, interleukin-6, interleukin 17A, and other cytokines at Singulex. This method utilizes single-photon counting of visible light to improve assay sensitivity. Separately, CLCS will determine hsCRP.
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Diagnosis of metabolic syndrome, as determined by at least three of the following five criteria:
Exclusion Criteria:
Prior travel treatment with chloroquine or hydroxychloroquine as follows:
Contacts and Locations| Contact: Janet B. McGill, MD | 314-362-8688 | jmcgill@dom.wustl.edu |
| Contact: Clay F. Semenkovich, MD | 314-362-7617 | csemenko@dom.wustl.edu |
| United States, Missouri | |
| Washington University School of Medicine | Recruiting |
| St. Louis, Missouri, United States, 63110 | |
| Contact: Stacy Hurst, RN 314-747-3294 shurst@dom.wustl.edu | |
| Contact: Danna Conboy 314-362-8285 dconboy@dom.wustl.edu | |
| Sub-Investigator: Janet B. McGill, MD | |
| Principal Investigator: | Clay F. Semenkovich, MD | Washington University School of Medicine |
More Information
| Responsible Party: | Washington University ( Clay Semenkovich, MD; Professor of Medicine, Director of the Division of Endocrinology, Metabolism and Lipid Research ) |
| Study ID Numbers: | 482, P50 HL083762-01 |
| Study First Received: | March 30, 2007 |
| Last Updated: | July 24, 2009 |
| ClinicalTrials.gov Identifier: | NCT00455403 History of Changes |
| Health Authority: | United States: Federal Government |
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Metabolic Syndrome Atherosclerosis |
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Anti-Inflammatory Agents Atherosclerosis Anti-Infective Agents Prediabetic State Overweight Arteriosclerosis Body Weight Antimalarials Signs and Symptoms Hyperinsulinism Anti-Inflammatory Agents, Non-Steroidal Analgesics Metabolic Disorder Dyslipidemias Arterial Occlusive Diseases |
Metabolic Diseases Metabolic Syndrome X Diabetes Mellitus Vascular Diseases Stress Endocrine System Diseases Chloroquine Anthelmintics Abdominal Obesity Metabolic Syndrome Analgesics, Non-Narcotic Chloroquine diphosphate Peripheral Nervous System Agents Insulin Resistance Endocrinopathy Antirheumatic Agents |
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Anti-Inflammatory Agents Atherosclerosis Anti-Infective Agents Antiprotozoal Agents Physiological Effects of Drugs Prediabetic State Overweight Arteriosclerosis Body Weight Antimalarials Signs and Symptoms Hyperinsulinism Antiparasitic Agents Pathologic Processes Sensory System Agents |
Therapeutic Uses Syndrome Anti-Inflammatory Agents, Non-Steroidal Cardiovascular Diseases Analgesics Amebicides Dyslipidemias Antinematodal Agents Arterial Occlusive Diseases Disease Metabolic Syndrome X Metabolic Diseases Filaricides Vascular Diseases Diabetes Mellitus |
