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

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ClinicalTrials.gov Identifier: NCT02776397
Recruitment Status : Unknown
Verified May 2016 by Tan Tock Seng Hospital.
Recruitment status was:  Recruiting
First Posted : May 18, 2016
Last Update Posted : May 19, 2016
Sponsor:
Collaborators:
Lee Kong Chian School of Medicine, Nanyang Technological University
National Medical Research Council (NMRC), Singapore
Information provided by (Responsible Party):
Tan Tock Seng Hospital

Brief 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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus Dietary Supplement: Vitamin E Other: Placebo Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Relationship of Haptoglobin Phenotype to Vascular Function and Response to Vitamin E Supplementation in Patients With Diabetes Mellitus Type 2: The EVAS Trial
Study Start Date : June 2015
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : July 2018


Arm Intervention/treatment
Active Comparator: Hp 2-2 Vitamin E
The Haptoglobin 2-2 group randomised to Vitamin E
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 Name: alpha tocopherol

Placebo Comparator: Hp 2-2 Placebo
The Haptoglobin 2-2 group randomised to placebo
Other: Placebo
Placebo arm

Active Comparator: Non Hp 2-2 Vitamin E
The Non Haptoglobin 2-2 group randomised to Vitamin E
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 Name: alpha tocopherol

Placebo Comparator: Non Hp 2-2 Placebo
The Non Haptoglobin 2-2 group randomised to placebo
Other: Placebo
Placebo arm




Primary Outcome Measures :
  1. Endothelial function [ Time Frame: 6 months ]
    Measured as Reactive hyperemia index using RHI-EndoPAT

  2. Aortic artery stiffness [ Time Frame: 6 months ]
    Measured as pulse wave velocity using the sphygmocor device

  3. Carotid Artery Intima Media Thickness [ Time Frame: 6 months ]
    Measured as CIMT (average) in mm.

  4. Inflammation [ Time Frame: 6 months ]
    Measured as hs-CRP

  5. Oxidative Stress [ Time Frame: 6 months ]
    Measured as oxidative stress index


Secondary Outcome Measures :
  1. Glycemic status [ Time Frame: 6 months ]
    Measured as HbA1c

  2. Retinal arteriovenous index [ Time Frame: 6 months ]
    Measured as ratio between retinal arterial diameter and venous diameter as retinal AV index

  3. Non HDL-Cholesterol [ Time Frame: 6 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Study patients should meet the following criteria for inclusion in the study:

  1. 100 Chinese, 100 Malays, 100 Indian patients with DM2
  2. Age 21-80 years
  3. Able to give informed consent
  4. Stable diabetes, blood pressure and hyperlipidaemia medications (a 25% dose adjustment is allowed) in the last three months
  5. For eligibility to be randomized: HbA1c should be 10% inclusive or below at time of randomisation
  6. Blood Pressure should be less than 180/120 mm Hg at time of recruitment
  7. Non-smokers or discontinued smoking at least 6 months ago
  8. No h/o previous myocardial infarction, previous cerebrovascular accident inclusive of haemorrhage and infarction, or h/o of peripheral amputation or bypass procedures

Exclusion Criteria:

  1. Inability to give informed consent
  2. Pregnant subjects
  3. Patients hospitalized for any condition less than 1 month from enrolment
  4. Patients having any recent infections or symptoms suggestive of any systemic infection in the last 2 weeks
  5. Myocardial Infarction or stroke within 6 months before enrolment
  6. Patients with creatinine concentrations >200 µmol/L or eGFR<30 µmol/L
  7. Patients on anticoagulants such as warfarin
  8. Known allergy to vitamin E
  9. Current smokers
  10. h/o previous myocardial infarction, previous cerebrovascular accident inclusive of haemorrhage and infarction, or h/o of peripheral amputation or bypass procedures
  11. Patients on immunosuppressive agents or corticosteroids for other conditions
  12. Presence of concomitant malignancies or rheumatological conditions at the time of recruitment
  13. Patients taking orlistat & cholestyramine

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): NCT02776397


Contacts
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Contact: Rinkoo Dalan, MBBS, FRCP (Edin) 63571000 ext 7884 rinkoo_dalan@ttsh.com.sg
Contact: Huiling Liew, MBBS, MRCP(UK) 63571000 huiling_liew@ttsh.com.sg

Locations
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Singapore
Tan Tock Seng Hospital Recruiting
Singapore, Singapore, 308433
Contact: Rinkoo Dalan, MBBS,FRCP    65-81263176    rinkoo_dalan@ttsh.com.sg   
Principal Investigator: Rinkoo Dalan, MBBS,FRCP         
Sponsors and Collaborators
Tan Tock Seng Hospital
Lee Kong Chian School of Medicine, Nanyang Technological University
National Medical Research Council (NMRC), Singapore
Investigators
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Principal Investigator: Rinkoo Dalan, MBBS, FRCP(Edin) Senior Consultant

Publications:
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Responsible Party: Tan Tock Seng Hospital
ClinicalTrials.gov Identifier: NCT02776397     History of Changes
Other Study ID Numbers: EVAS001 Version 4
First Posted: May 18, 2016    Key Record Dates
Last Update Posted: May 19, 2016
Last Verified: May 2016

Additional relevant MeSH terms:
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Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents