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

Phase 2

Completed

• Conditions: Diabetes, Type I
• Interventions: Drug: Actrapid HM

• Registration Number: NCT00654121
• Lead Sponsor: AZ-VUB

Brief Summary

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).

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 Timeline

• Study Start: 2000-02
• Primary Completion: 2004-04
• Study Completion: 2007-11
• Status Verified: 2008-04
• Study First Submitted: 2008-04-02
• Study First Submitted QC: 2008-04-04
• Last Update Submitted: 2008-04-04
• Study First Posted: 2008-04-07
• Last Update Posted: 2008-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Actrapid HM	56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)

Primary Outcome Measures

Name	Time	Method
Fasting glycemia;	2004
fasting and stimulated plasma C-peptide and proinsulin values;	2004
islet cell autoantibodies;	2004
body weight gain.	2004

Trial Locations

Locations (3)

Department of Endocrinology and Nephrology, UZ Gasthuisberg, Katholieke Universiteit Leuven -KUL; 🇧🇪 Leuven, Belgium

Academisch Ziekenhuis and Diabetes Research Center - Brussels Free University-VUB; 🇧🇪 Brussels, Belgium

Universitair Ziekenhuis Antwerpen; 🇧🇪 Antwerpen, Belgium