Prevention of Cardiovascular Complications in Diabetic Patients With Vitamin E Treatment

Terminated

Phase 2/3 Results N/A

Trial Description

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.

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.

Trial Stopped: interim analysis showed significant differences between two treatment groups

Conditions

Interventions

Trial Design

  • Allocation: Randomized
  • Masking: Double-Blind
  • Purpose: Prevention
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary A combination of CVD mortality non fatal MI and Stoke at a 4 year follow up.
Secondary Cardiac Interventions (Angioplasty, Bypass surgery
Secondary etc…), all cause mortality, heart failure, at a 4 year follow up.

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