Relationship of Haptoglobin Phenotype to Vascular Function and Response to Vitamin E Supplementation in Patients With Diabetes Mellitus Type 2: The EVAS Trial

Summary

Relationship of haptoglobin phenotype to vascular function and response to Vitamin E supplementation in Patients with Diabetes Mellitus Type 2: The EVAS Trial

Specific Aims:

The phenotype haptoglobin 2-2 (Hp 2-2) is associated with higher oxidative stress, inflammation, LDL peroxidation and higher cardiovascular risk in patients with diabetes. We aim to determine whether Hp 2-2 phenotype is associated with surrogate markers of cardiovascular risk, inflammation, lipids and lipoprotein profile, oxidative stress, and endothelial cell (EC) apoptosis (in vitro study) in patients with diabetes in our population and whether vitamin E supplementation mitigates this risk.

Methods:

Screening Phase:

We will recruit 300 patients with diabetes mellitus type 2 (100 Chinese, 100 Malays and 100 Indians) and assess their Hp phenotype, surrogate markers of cardiovascular risk, inflammation, vascular biomarkers and lipids phenotype.

In vitro Study:

Plasma from 20 patients with Hp 2-2 phenotype and 20 patients with non Hp 2-2 phenotype will be studied in vitro using a haemodynamic lab-on-chip system to determine whether there is a difference in EC apoptosis between the two groups.

Randomisation Phase 200 patients will be recruited to a pilot randomized controlled trial (RCT), stratified by Hp 2-2 phenotype status (100 Hp 2-2 and 100 non-Hp 2-2), and randomly allocated in a 1:1 ratio to either vitamin E 400 IU supplementation daily for 6 months or a placebo group. The trial will determine whether vitamin E improves the aforementioned surrogate markers in the Hp phenotype strata.

Importance of proposed research to science and medicine:

This study allows us to understand the possible mechanism of cardiovascular risk in patients with Hp 2-2 phenotype and to see whether vitamin E supplementation reduces this risk in a pharmacogenomic targeted manner.

Conditions

• Diabetes Mellitus

Interventions

DIETARY_SUPPLEMENT

Vitamin E

Two hundred patients will be recruited to a pilot randomized controlled trial (RCT), stratified by Hp 2-2 phenotype status (100 Hp 2-2 and 100 non-Hp 2-2), and randomly allocated in a 1:1 ratio to either vitamin E 400 IU supplementation daily for 6 months or a placebo group. The trial will determine whether vitamin E improves the aforementioned surrogate markers in the Hp phenotype strata.

OTHER

Placebo

Placebo arm

Sponsors & Collaborators

• Lee Kong Chian School of Medicine, Nanyang Technological University

  collaborator UNKNOWN

• National Medical Research Council (NMRC), Singapore

  collaborator OTHER_GOV

• Tan Tock Seng Hospital

  lead OTHER

Principal Investigators

• Rinkoo Dalan, MBBS, FRCP(Edin) · Senior Consultant

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-06-30

Primary Completion

2018-06-30

Completion

2018-07-31

Countries

• Singapore

Study Locations