Effect of Diabetes Mellitus on Cholesterol Metabolism - Full Text View

Sponsor:	Medical College of Wisconsin
Information provided by:	Medical College of Wisconsin
ClinicalTrials.gov Identifier:	NCT00879710

Purpose

HMG CoA reductase inhibitors (statins) are commonly used to treat high cholesterol (HC) in both type 1 and type 2 diabetes mellitus (DM). Several studies have shown benefits of statin among patients of type 2 DM, however, no such data is available for patients with type 1 DM.

It is known from studies on cholesterol metabolism using surrogate markers that patients with type 1 DM have higher cholesterol absorption compared to normals and those with type 2 DM have higher cholesterol synthesis. Since statins inhibit synthesis, patients with type 1 DM may not have a good response and may respond better to cholesterol absorption inhibitors. The purpose of this study is to determine the cholesterol lowering effects of cholesterol absorption inhibitors and cholesterol synthesis inhibitors in subjects with type 1 and type 2 diabetes mellitus.

Condition	Intervention
Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Hypercholesterolemia	Drug: simvastatin or ezetimibe

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Effect of Diabetes Mellitus on Cholesterol Absorption, Synthesis and Statin Efficacy

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus hypercholesterolemia

MedlinePlus related topics: Cholesterol Diabetes Diabetes Type 1 Diabetes Type 2 Statins

Drug Information available for: Cholest-5-en-3-ol (3beta)- Simvastatin Ezetimibe

U.S. FDA Resources

Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:

Lowering of LDL cholesterol [ Time Frame: 6 weeks after starting drug therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in cholesterol absorption or synthesis rates from the baseline [ Time Frame: 6 weeks after initiation of drug therapy ] [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	August 2008
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Subjects with type 1 diabetes mellitus	Drug: simvastatin or ezetimibe Subjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist. Other Name: Zocor or zetia
Subjects with type 2 diabetes mellitus	Drug: simvastatin or ezetimibe Subjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist. Other Name: Zocor or zetia

Arms

Assigned Interventions

Subjects with type 1 diabetes mellitus

Drug: simvastatin or ezetimibe

Subjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist.

Other Name: Zocor or zetia

Subjects with type 2 diabetes mellitus

Drug: simvastatin or ezetimibe

Subjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist.

Other Name: Zocor or zetia

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Type 1 DM:
Age > 18 years
Subjects diagnosed with type 1 DM (diagnosed based upon history of ketoacidosis, proven insulin dependence, absent C-peptide and or positive autoantibody profile (such as anti-GAD etc.)
Stable A1C < 8.5%
BMI < 31
Type 2 DM:
Age > 18 years
Subjects diagnosed with type II DM (diagnosed as adult onset, not-insulin dependent and not on insulin)
Stable A1C < 8.5%
BMI < 31

Exclusion Criteria:

History of active, unstable cardiovascular disease (including MI, CHF, Stroke, Angina, CABG, stenting/PTCA, peripheral vascular disease, intermittent claudication)
Pregnancy, nursing or likely to get pregnant during the course of the study (not on oral contraceptives and premenopausal)
Chronic Kidney Disease (creatinine > 2.0)
Liver function test abnormalities, not previously worked up (AST or ALT >4x upper limit of normal)
Active substance abuse including alcohol
History of severe Hypertriglyceridemia (untreated TG > 500) and on therapy
Use of agents that interfere with cholesterol absorption (such as fiber, resins etc.) which can not be discontinued for the duration of the study
Actively enrolled in a weight loss program or following a special diet ( e.g.: Atkins diet)
History of malignancy <5y
History of Rhabdomyolysis and Myopathy
Use of on-going oral corticosteroids
History of HIV infection
Use of following drugs/compounds: cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, niacin, amiodarone, verapamil or large quantities of grape fruit juice (> 1 quart per day)
Proteinuria: more than or equal to 300mg/24 hours calculated from random urine specimen.
BMI >31
Anyone with hypersensitivity to either one of the study medications
Allergy to Soy bean products
Unable to consume milk products with or without Lactaid®

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879710

Contacts

Contact: Gerard Coly, MD

414-456-7438

gcoly@mcw.edu

Locations

United States, Wisconsin
Medical College of Wisconsin /Froedtert Hospital	Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Gerard Coly, Md 414-456-7438 gcoly@mcw.edu
Contact: Srividya Kidambi, MD 414-955-6724 skidambi@mcw.edu
Principal Investigator: Shailendra B Patel, MD, PhD
Sub-Investigator: Srividya Kidambi, MD

Sponsors and Collaborators

Medical College of Wisconsin

Investigators

Principal Investigator:	Shailendra B Patel, MD, PhD	Medical College of Wisconsin
Principal Investigator:	Srividya Kidambi, MD	Medical College of Wisconsin

More Information

No publications provided

Responsible Party:	S. Kidambi MD and Shailendra Patel ,MD PhD, Medical College of Wisconsin
ClinicalTrials.gov Identifier:	NCT00879710 History of Changes
Other Study ID Numbers:	PRO00002485
Study First Received:	April 8, 2009
Last Updated:	July 26, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:

Diabetes Mellitus
Hypercholesterolemia
Simvastatin
Ezetimibe.

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Hypercholesterolemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders

Simvastatin
Ezetimibe
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012