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Prevention of Cardiovascular Complications in Diabetic Patients With Vitamin E Treatment

This study has been terminated.
(interim analysis showed significant differences between two treatment groups)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00220831
First Posted: September 22, 2005
Last Update Posted: March 1, 2007
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.
Collaborators:
Clalit Health Services
Kennedy-Leigh charitable trust
Information provided by:
Technion, Israel Institute of Technology
  Purpose
The purpose of this study is to determine whether Vitamin E treatment to Diabetic patients, who carry the Haptoglobin 2-2 Phenotype, prevents cardiovascular complications such as acute MI and Stroke.

Condition Intervention Phase
Diabetes Myocardial Infarction Cardiovascular Disease Drug: Natural source Vitamin E 400IU/day Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Prevention
Official Title: Prevention of Diabetic Cardiovascular Complications With Vitamin E 400 IU Treatment to High Risk Patients by Haptoglobin Phenotype (I CARE – Israel Cardiovascular Atherosclerosis Risk and Vitamin E)

Resource links provided by NLM:


Further study details as provided by Technion, Israel Institute of Technology:

Primary Outcome Measures:
  • A combination of CVD mortality non fatal MI and Stoke at a 4 year follow up.

Secondary Outcome Measures:
  • Cardiac Interventions (Angioplasty, Bypass surgery
  • etc…), all cause mortality, heart failure, at a 4 year follow up.

Estimated Enrollment: 2000
Study Start Date: April 2005
Estimated Study Completion Date: December 2009
Detailed Description:

Haptoglobin is a free Hemoglobin scavenger protein. Hemoglobin is an oxidant due to the Fe it carries by the Fenton reaction. Thus it is believed that Haptoglobin is an antioxidant, especially in the site of vascular injury.

Haptoglobin has three phenotype easily identified by a method of gel electrophoresis.

The three phenotype denote as 1-1, 2-1 and 2-2. We have found in several in vitro studies in our lab that Haptoglobin 1-1 is a superior antioxidant over 2-2.

In several large retrospective studies we found that Diabetic patients who are Haptoglobin typed 2-2 have a 5 time risk of having cardiovascular complications (acute MI, CVA, CVD death) over the ones who are Haptoglobin 1-1.

2-1 patients are probably at intermediate risk. While retrospectively typing consecutive serums from patients who participate the HOPE study we found that taking Vitamin E decreased by 50% the CVD incidences of Diabetic patients with the Haptoglobin 2-2 phenotype.

Based on these findings we wish to perform the I CARE study. 5000 diabetic patients aged 55 and above, will be tested for Haptoglobin phenotype.

Knowing the distribution of the different Haptoglobin phenotypes in the Israeli population we estimate that about 2000 will be of the phenotype 2-2.

These 2000 patients will be enrolled in a prospective, doubled blind, randomized and placebo controlled clinical study and will be randomly divided into 2 groups, one receiving Vitamin E 400IU per day and the other receiving matching placebo.

All patients will be followed routinely by their primary physicians in Clalit HMO (the biggest HMO in Israel) in a routine diabetes follow up and treatment (HbA1c, blood pressure control, Lipids, renal function, eye exam for retinopathy etc…) The study steering committee will get anamnestic data and routine tests results every 3 months.

Primary Outcomes: a combination of CVD mortality and non fatal MI and Stroke. Secondary Outcomes: Cardiac Interventions (Angioplasty, Bypass surgery etc…), all cause mortality, heart failure.

Exclusion criteria: 1) patient who takes antioxidant treatment will be asked to stop, or can't be included in the study.

2) Patients who had a CVD incident (MI, Stroke, TIA), Unstable angina pectoris, Uncontrolled HTN, will have to wait a month after stabilization to be included in the study.

3) Allergy to Vitamin E. Follow up duration – 4.5 years. 5% percent of all vitamin receivers will be tested at base line and a year after enrollment, for Vitamin E plasma concentration.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diabetic patients aged 55 and above

Exclusion Criteria:

  • Patient who takes antioxidant treatment will be asked to stop, or can't be included in the study
  • Patients who had a CVD incident (MI, Stroke, TIA), Unstable angina pectoris, Uncontrolled HTN, will have to wait a month after stabilization to be included in the study
  • Allergy to Vitamin E
  Contacts and Locations
Information from the National Library of Medicine

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): NCT00220831


Locations
Israel
Clalit Health Services, Haifa and West Galilee - primary health care clinics, in the north of Israel And the Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Haifa, Israel
Sponsors and Collaborators
Technion, Israel Institute of Technology
Clalit Health Services
Kennedy-Leigh charitable trust
Investigators
Principal Investigator: Uzi Milman, MD Clalit Health Services
Study Chair: Chen Shapira, MD Clalit Health Services
Study Chair: Shany Blum, MD MSc Laboratory of Vascular Medicine, the Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology.
Study Chair: Andrew P Levy, MD PhD Laboratory of Vascular Medicine, the Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology.
  More Information

Publications:
Melamed-Frank M, Lache O, Enav BI, Szafranek T, Levy NS, Ricklis RM, Levy AP. Structure-function analysis of the antioxidant properties of haptoglobin. Blood. 2001 Dec 15;98(13):3693-8.
Levy AP, Roguin A, Hochberg I, Herer P, Marsh S, Nakhoul FM, Skorecki K. Haptoglobin phenotype and vascular complications in patients with diabetes. N Engl J Med. 2000 Sep 28;343(13):969-70.
Nakhoul FM, Marsh S, Hochberg I, Leibu R, Miller BP, Levy AP. Haptoglobin genotype as a risk factor for diabetic retinopathy. JAMA. 2000 Sep 13;284(10):1244-5.
Nakhoul FM, Zoabi R, Kanter Y, Zoabi M, Skorecki K, Hochberg I, Leibu R, Miller B, Levy AP. Haptoglobin phenotype and diabetic nephropathy. Diabetologia. 2001 May;44(5):602-4.
Roguin A, Hochberg I, Nikolsky E, Markiewicz W, Meisel SR, Hir J, Grenadier E, Beyar R, Levy AP. Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol. 2001 Feb 1;87(3):330-2, A9.
Levy AP, Hochberg I, Jablonski K, Resnick HE, Lee ET, Best L, Howard BV; Strong Heart Study. Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol. 2002 Dec 4;40(11):1984-90.
Hochberg I, Roguin A, Nikolsky E, Chanderashekhar PV, Cohen S, Levy AP. Haptoglobin phenotype and coronary artery collaterals in diabetic patients. Atherosclerosis. 2002 Apr;161(2):441-6.
Levy AP, Gerstein HC, Miller-Lotan R, Ratner R, McQueen M, Lonn E, Pogue J. The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. Diabetes Care. 2004 Nov;27(11):2767.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00220831     History of Changes
Other Study ID Numbers: KL-2004
First Submitted: September 13, 2005
First Posted: September 22, 2005
Last Update Posted: March 1, 2007
Last Verified: February 2007

Keywords provided by Technion, Israel Institute of Technology:
Diabetes
MI
CVD disease

Additional relevant MeSH terms:
Infarction
Cardiovascular Diseases
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Vascular Diseases
Vitamins
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents


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