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

This study has been completed.
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Tina Costacou, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01098994
First received: February 24, 2010
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Type 1 Diabetes
Heart Disease
Dietary Supplement: Vitamin E
Other: Dummy pills

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot and Feasibility Study for a Pharmacogenomic Trial in Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Feasibility of recruitment of individuals with type 1 diabetes for a randomized clinical trial [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 87
Study Start Date: February 2010
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Natural d-alpha tocopherol acetate
Other: Dummy pills
Daily placebo administration for 8 weeks
Other Name: Placebo, inactive pills
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 Name: Natural d-alpha tocopherol acetate
Other: Dummy pills
Daily placebo administration for 8 weeks
Other Name: Placebo, inactive pills
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 Name: Natural d-alpha tocopherol acetate
Other: Dummy pills
Daily placebo administration for 8 weeks
Other Name: Placebo, inactive pills

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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01098994

Locations
United States, Pennsylvania
University of Pittsburgh Diabetes and Lipid Research Clinic
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
American Diabetes Association
Investigators
Principal Investigator: Tina Costacou, PhD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Tina Costacou, Assistant Professor of Epidemiology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01098994     History of Changes
Other Study ID Numbers: 1-10-CT-12, 1-10-CT-12
Study First Received: February 24, 2010
Last Updated: June 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Type 1 diabetes
Haptoglobin genotype
HDL function
Heart disease
Feasibility of clinical trial

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Heart Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Cardiovascular Diseases
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 27, 2014