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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Diabetes, Type I

Intervention / Treatment
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* Drug: Actrapid HM


Participation Criteria
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Eligibility Criteria
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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): Normal glycemia: fasting plasma glucose < 110 mg/dL and 2 hour plasma glucose < 140 mg/dL Impaired Fasting Glucose (IFG): fasting plasma glucose 110-125 mg/dL and 2 hour plasma glucose < 140 mg/dL 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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily) | Drug: Actrapid HM<br>* 56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)<br>|
| No Intervention: 2<br> | |

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prevention