Prevention of Clinical Onset of Type 1 Diabetes in High Risk First Degree Relatives

April 4, 2008 updated by: AZ-VUB

Prevention of Clinical Onset of Type 1 Diabetes by Daily Administration of Metabolically Active Insulin in High Risk First Degree Relatives.

Prophylactic administration of metabolically active insulin can prevent or delay clinical onset of diabetes in a high risk group of nondiabetic siblings as defined by positivity for autoantibodies against IA-2 (IA-2-A).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hypotheses:

Primary: Prophylactic administration of metabolically active insulin can prevent or delay clinical onset of diabetes in a high risk group of nondiabetic siblings as defined by positivity for autoantibodies against IA-2 (IA-2-A).

Secondary: 1) Untreated siblings with positivity for IA-2-A develop clinical diabetes significantly faster than untreated offspring with the same marker positivity. 2) Plasma proinsulin levels increase disproportionately before clinical onset of Type 1 diabetes both in siblings and offspring. 3) Prophylactic administration of metabolically active insulin reduces the plasma proinsulin/C-peptide ratio in non-diabetic antibody positive siblings and offspring. 4) Prophylactic administration of metabolically active insulin reduces the presence and/or levels of diabetes-associated autoantibodies directed against islet cell components.

Endpoints: Fasting glycemia; fasting and stimulated plasma C-peptide and proinsulin values; islet cell autoantibodies; incidence of hypoglycemia; body weight gain.

Study Type

Interventional

Enrollment (Actual)

112

Phase

  • Phase 2

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

      • Antwerpen, Belgium
        • Universitair Ziekenhuis Antwerpen
      • Brussels, Belgium, 1090
        • Academisch Ziekenhuis and Diabetes Research Center - Brussels Free University-VUB
      • Leuven, Belgium, 3000
        • Department of Endocrinology and Nephrology, UZ Gasthuisberg, Katholieke Universiteit Leuven -KUL

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

5 years to 39 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Sibling/offspring of a Type 1 diabetic patient
  • in good general condition
  • age 5-39 years
  • fasting plasma glucose <126 mg/dL AND an OGTT that is non-diabetic by 1997 ADA criteria (33):

    1. Normal glycemia:

      • fasting plasma glucose < 110 mg/dL and
      • 2 hour plasma glucose < 140 mg/dL
    2. Impaired Fasting Glucose (IFG):

      • fasting plasma glucose 110-125 mg/dL and
      • 2 hour plasma glucose < 140 mg/dL
    3. Impaired Glucose Tolerance (IGT):

      • fasting plasma glucose <110 mg/dL and
      • 2 hour plasma glucose 140-199 mg/dL
  • at least positive for IA-2-A
  • absence of a protective DQ genotype: A4-B2/X or X/Y or X/X where X = A2-B3.3, A1-B1.9, A1-B1.2, A4-B3.1, A2-B2 or A4.23-B3.1 Y = A1-B1.1, A1-B2, A1-B1.AZH, A3-B2, A3-B3.1, A3-B3.3, A3-B4, A4-B4, A4.23-B4, A4-B3.2, A3-B1.1, A4-B3.3, A4-B1.1 or A4.23-B2 (32)
  • cooperative and reliable subject (age ≥ 14 yrs) / parents (age < 14 yrs) giving informed consent by signature; the patient/parents should be informed in sufficient detail on the content and procedure of the protocol, indicating potential risks of insulin therapy; early intervention with metabolically active insulin treatment should be identified as a clinical trial. Both parents should sign and agree with the protocol procedure.

Exclusion Criteria:

  • diabetes by 1997 ADA criteria (33):

    • fasting plasma glucose ≥ 126 mg/dL, or
    • 2 hour plasma glucose ≥ 200 mg/dL
  • donation of blood during the study or within one month prior to screening
  • pregnancy or lactation in women
  • use of inadequate anticonception by female patients of childbearing potential
  • use of illicit drugs or overconsumption of alcohol (> 3 beers/day) or history of drug or alcohol abuse
  • being legally incapacitated, having significant emotional problems at the time of the study, or having a history of psychiatric disorders
  • having received antidepressant medications during the last 6 months
  • treatment with immune modulating or diabetogenic medication (such as corticosteroids)
  • presently participating in another clinical study or having done so during the last 12 months
  • history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient

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: Prevention
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: 2
Active Comparator: 1
56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)
56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Fasting glycemia;
Time Frame: 2004
2004
fasting and stimulated plasma C-peptide and proinsulin values;
Time Frame: 2004
2004
islet cell autoantibodies;
Time Frame: 2004
2004
body weight gain.
Time Frame: 2004
2004

Collaborators and Investigators

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

Sponsor

Collaborators

Investigators

  • Principal Investigator: Frans Gorus, MD,PhD, Universitair Ziekenhuis Brussel
  • Principal Investigator: Evy Vandemeulebroucke, MD, Universitair Ziekenhuis Brussel

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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, 2000

Primary Completion (Actual)

April 1, 2004

Study Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

April 2, 2008

First Submitted That Met QC Criteria

April 4, 2008

First Posted (Estimate)

April 7, 2008

Study Record Updates

Last Update Posted (Estimate)

April 7, 2008

Last Update Submitted That Met QC Criteria

April 4, 2008

Last Verified

April 1, 2008

More Information

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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