Effect of Diabetes Mellitus on Cholesterol Metabolism
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00879710 |
|
Recruitment Status :
Completed
First Posted : April 10, 2009
Results First Posted : April 18, 2016
Last Update Posted : April 18, 2016
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Hypercholesterolemia | Drug: simvastatin or ezetimibe | Not Applicable |
Show Detailed Description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 57 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Effect of Diabetes Mellitus on Cholesterol Absorption, Synthesis and Statin Efficacy |
| Study Start Date : | August 2008 |
| Actual Primary Completion Date : | July 2013 |
| Actual Study Completion Date : | July 2013 |
| Arm | Intervention/treatment |
|---|---|
|
Subjects with type 1 diabetes mellitus,
Half the subjects will start with arm (i.e. every other subject in order)
Half the subjects will start with arm (i.e. every other subject in order)
|
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
Half the subjects will start with arm (i.e. every other subject in order)
Half the subjects will start with arm (i.e. every other subject in order)
|
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 |
- Changes in LDL Cholesterol [ Time Frame: 6 weeks after starting drug therapy ]
Subjects with T1DM or T2DM were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design.
The data are reported as follows.
Subjects with type 1 diabetes mellitus:
Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order)
Subjects with type 2 diabetes mellitus:
Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order)
- Changes in Cholesterol Absorption or Synthesis Rates From the Baseline [ Time Frame: 6 weeks after initiation of drug therapy ]We did not complete analyses of this outcome as we ran out of funds to measure these variables though samples have been collected.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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®
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00879710
| United States, Wisconsin | |
| Medical College of Wisconsin /Froedtert Hospital | |
| Milwaukee, Wisconsin, United States, 53226 | |
| Principal Investigator: | Srividya Kidambi, MD | Medical College of Wisconsin | |
| Principal Investigator: | Shailendra B Patel, MD, PhD | Medical College of Wisconsin |
Publications of Results:
| Responsible Party: | Srividya Kidambi, MD, Assistant Professor, Endocrinology, Medical College of Wisconsin |
| ClinicalTrials.gov Identifier: | NCT00879710 History of Changes |
| Other Study ID Numbers: |
PRO00002485 |
| First Posted: | April 10, 2009 Key Record Dates |
| Results First Posted: | April 18, 2016 |
| Last Update Posted: | April 18, 2016 |
| Last Verified: | March 2016 |
Keywords provided by Srividya Kidambi, MD, Medical College of Wisconsin:
|
Diabetes Mellitus Hypercholesterolemia Simvastatin Ezetimibe. |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Diabetes Mellitus, Type 1 Hypercholesterolemia Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Hyperlipidemias Dyslipidemias |
Lipid Metabolism Disorders Simvastatin Ezetimibe Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors |