Haptoglobin Phenotype, Vitamin E and High-density Lipoprotein (HDL) Function in Type 1 Diabetes (HAP-E)

June 2, 2014 updated by: Tina Costacou, University of Pittsburgh

Pilot and Feasibility Study for a Pharmacogenomic Trial in Type 1 Diabetes

The purpose of the study is to determine whether the function of the good cholesterol (HDL cholesterol) as well as its subfractions (via NMR spectroscopy) is altered among people with type 1 diabetes and a variation in the Haptoglobin gene and to evaluate whether vitamin E supplements may improve this function.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Persons with type 1 diabetes are at a much greater risk for heart disease compared to the general population. Among individuals with diabetes, those with a specific variation in a genetic marker called Haptoglobin (approximately 43% of persons with type 1 diabetes) are at even greater risk compared to those not carrying this genetic variation. A genetic marker or a "gene" is information inherited from parents (a blueprint) about the structure and functions of cells in the body that make up the color of our hair and eyes and may influence the way our bodies respond to certain stimuli such as an illness, or infection.

In this project we are seeking to understand what some of the mechanisms may be that put persons with type 1 diabetes and this variation in the Haptoglobin gene at greater risk for heart disease. Specifically, we will assess whether this gene variant affects the function of the good cholesterol (HDL cholesterol) and its subfractions (via NMR spectroscopy), which is thought to help against heart disease development. We also seek to evaluate whether vitamin E supplements may improve this function. If results indicate that vitamin E is beneficial and improves the function of HDL cholesterol, the next question to be answered would be whether vitamin E would also help reduce the risk of heart disease itself in these persons. To answer the latter, a large clinical trial would have to take place. In this research project we will therefore also evaluate whether such a trial would be feasible and whether individuals with type 1 diabetes would be interested in participating in a long, 4-5 year, clinical trial.

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Diabetes and Lipid Research Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Individuals with type 1 diabetes residing in the Pittsburgh, PA area (members of the Allegheny Count or Children's Hospital of Pittsburgh/Epidemiology of Diabetes Complications Registries)
  • 30 years old or older
  • with diabetes duration greater than 10 years or less than 10 years but with a history of heart disease

Exclusion Criteria:

  • Allergy to vitamin E
  • Stroke, MI within the past 6 months
  • Unwillingness/inability to limit antioxidant supplement use to study-provided supplements

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Haptoglobin 1/1
Individuals with type 1 diabetes and the Haptoglobin 1/1 phenotype
Dietary supplement: Vitamin E
Daily administration of 400 IU natural d-alpha tocopherol acetate for 8 weeks
Other Names:
  • Natural d-alpha tocopherol acetate
Other: Dummy pills
Daily placebo administration for 8 weeks
Other Names:
  • Placebo, inactive pills
Other: Haptoglobin 2/1
Individuals with type 1 diabetes and the Haptoglobin 2/1 phenotype
Dietary supplement: Vitamin E
Daily administration of 400 IU natural d-alpha tocopherol acetate for 8 weeks
Other Names:
  • Natural d-alpha tocopherol acetate
Other: Dummy pills
Daily placebo administration for 8 weeks
Other Names:
  • Placebo, inactive pills
Other: Haptoglobin 2/2
Individuals with type 1 diabetes and the Haptoglobin 2/2 phenotype
Dietary supplement: Vitamin E
Daily administration of 400 IU natural d-alpha tocopherol acetate for 8 weeks
Other Names:
  • Natural d-alpha tocopherol acetate
Other: Dummy pills
Daily placebo administration for 8 weeks
Other Names:
  • Placebo, inactive pills

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demonstrate the presence of HDL dysfunction among individuals with the Haptoglobin 2/1 and 2/2 compared to those with the Hp 1/1 phenotype and improvement in HDL dysfunction with natural d-α-tocopherol supplementation
Time Frame: 6 months
HDL-associated lipid peroxides, HDL function (based on its ability to promote cholesterol efflux from macrophages), HDL antioxidant and anti-inflammatory activities; NMR lipoprotein subfractions will be assessed
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of recruitment of individuals with type 1 diabetes for a randomized clinical trial
Time Frame: 1 year
Members of two registries (ACR and CHP/EDC) residing within 100 miles or 2.5 hours driving distance from Pittsburgh, Pennsylvania will be contacted and interest for participation in a trial will be assessed as part of the original registry's follow-up. Investigators will contact those interested, explain the study aims and scope, and further assess willingness and eligibility for participation in a clinical trial.
1 year
Assessment of adherence to the clinical trial study protocol in a random sample of individuals with type 1 diabetes recruited from the ACR and CHP/EDC Diabetes Registries
Time Frame: 6 months
Protocol adherence will be evaluated by clinic attendance, pill count and by comparison of plasma α-tocopherol concentrations at baseline with plasma levels after vitamin E supplementation or placebo.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

American Diabetes Association

Investigators

  • Principal Investigator: Tina Costacou, PhD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2010

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

February 24, 2010

First Submitted That Met QC Criteria

April 2, 2010

First Posted (Estimate)

April 6, 2010

Study Record Updates

Last Update Posted (Estimate)

June 3, 2014

Last Update Submitted That Met QC Criteria

June 2, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1-10-CT-12 (Other Grant/Funding Number: American Diabetes Association)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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