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:
Collaborators:
Clalit Health Services
Kennedy-Leigh charitable trust
Information provided by:
Technion, Israel Institute of Technology
ClinicalTrials.gov Identifier:
NCT00220831
First received: September 13, 2005
Last updated: February 28, 2007
Last verified: February 2007
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

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

Additional 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
Study First Received: September 13, 2005
Last Updated: February 28, 2007
Health Authority: Israel: Ministry of Health

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

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

ClinicalTrials.gov processed this record on October 23, 2014