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

This study has been completed.
Sponsor:
Collaborator:
Novo Nordisk
Information provided by:
AZ-VUB
ClinicalTrials.gov Identifier:
NCT00654121
First received: April 2, 2008
Last updated: April 4, 2008
Last verified: April 2008
History of Changes
  Purpose

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).


Condition Intervention Phase
Diabetes, Type I
 Drug: Actrapid HM
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prevention of Clinical Onset of Type 1 Diabetes by Daily Administration of Metabolically Active Insulin in High Risk First Degree Relatives.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AZ-VUB:

Primary Outcome Measures:
  • Fasting glycemia; [ Time Frame: 2004 ] [ Designated as safety issue: No ]
  • fasting and stimulated plasma C-peptide and proinsulin values; [ Time Frame: 2004 ] [ Designated as safety issue: No ]
  • islet cell autoantibodies; [ Time Frame: 2004 ] [ Designated as safety issue: No ]
  • body weight gain. [ Time Frame: 2004 ] [ Designated as safety issue: No ]

Enrollment: 112
Study Start Date: February 2000
Study Completion Date: November 2007
Primary Completion Date: April 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)
 Drug: Actrapid HM
56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)
No Intervention: 2

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.

  Eligibility

Ages Eligible for Study:   5 Years to 39 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00654121

Locations
Belgium
Universitair Ziekenhuis Antwerpen
Antwerpen, Belgium
Academisch Ziekenhuis and Diabetes Research Center - Brussels Free University-VUB
Brussels, Belgium, 1090
Department of Endocrinology and Nephrology, UZ Gasthuisberg, Katholieke Universiteit Leuven -KUL
Leuven, Belgium, 3000
Sponsors and Collaborators
AZ-VUB
Novo Nordisk
Investigators
Principal Investigator: Frans Gorus, MD,PhD Universitair Ziekenhuis Brussel
Principal Investigator: Evy Vandemeulebroucke, MD Universitair Ziekenhuis Brussel
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Prof. F Gorus, Free University Brussels
ClinicalTrials.gov Identifier: NCT00654121     History of Changes
Other Study ID Numbers: EVDM IT 001
Study First Received: April 2, 2008
Last Updated: April 4, 2008
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by AZ-VUB:
prevention

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on May 22, 2013