Risk for type 1 diabetes
Conditions
Interventions
Product Name: insulin human
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: INSULIN HUMAN
CAS Number: 11061-68-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration num
Sponsors
Technische Universität München, Fakultät für Medizin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent signed by either parent(s) or legal guardian(s). 2. Children aged 2 years to 12 years. 3. Positive for at least two islet autoantibodies out of autoantibodies to glutamic acid decarboxylase (GAD65), to insulin (IAA), autoantibodies to IA-2 (IA2A), or autoantibodies to zink transporter 8 (ZnT8A) (time between screening sample collection and randomization must not exceed 90 days). 4. Normoglycemia assessed by oral glucose tolerance test (OGTT). 5. Participation in an observational study that regularly monitors diabetes development Are the trial subjects under 18? yes Number of subjects for this age range: 220 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Dysglycaemia or overt hyperglycemia (diabetes) 2. Concomitant disease or treatment that may interfere with assessment or cause immunosuppression, as judged by the investigators. 3. Current participation in another intervention trial. 4. Any condition that could be associated with poor compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the immune efficacy, and treatment efficacy of daily high dose oral insulin (up to 67.5 mg) in children aged 2 years to 12 years with multiple islet autoantibodies in a secondary intervention study. Immune efficacy is defined as a change in the immune response to the treatment, which is associated with a reduction in the progression to dysglycemia or diabetes. Treatment efficacy is a treatment related reduction in the rate of progression to dysglycemia or diabetes.;Secondary Objective: NA;Primary end point(s): To determine whether daily administration of up to 67.5 mg insulin to young children aged 2 years to 12 years with multiple islet autoantibodies alters the immune responses to insulin. Immune response measures will be salivary IgA antibodies to insulin, blood CD4+ T responses to insulin, or autoantibodies to insulin (up to 12 months). Participants are categorized as immune responders if they show a change in at least one of these measures. If a treatment effect on responder status is observed in the first 90 participants, the analysis will proceed for all participants and the primary outcome of a change in immune response to insulin associated with reduced progression to dysglycemia or diabetes will be assessed in all participants. A co-primary outcome is to assess whether the treatment is associated with a reduced progression to dysglycemia or diabetes in all participants. ;Timepoint(s) of evaluation of this end point: at baseline, 3 months-, 6 months-, 9 months and 12 months of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To determine whether daily administration of up to 67.5 mg insulin induces metabolic changes in blood of safety concern in autoantibody positive children aged 2 years to 12 years. 2. Evaluate if daily administration of up to 67.5 mg insulin to young autoantibody positive children aged 2 years to 12 years with multiple islet autoantibodies may reduce the rate of disease progression to the end point clinical type 1 diabetes. 3. Determine whether daily administration of up to 67.5 mg insulin is associated with a difference in the gene expression in insulin-responsive CD4+ T cells.* 4. Determine whether daily administration of up to 67.5mg insulin is associated with a difference in serum insulin autoantibodies. 5. Determine whether daily administration of up to 67.5 mg insulin increases the frequency of insulin tetramer positive CD4+ regulatory T cells compared to the placebo group.* 6. Determine whether daily administration of up to 67.5 mg insulin modifies CD4+ T cells responses to insulin.* 7. Determine whether daily administration of up to 67.5 mg insulin modifies CD8+ T cells responses to insulin.* 8. Determine whether daily administration of up to 67.5 mg insulin modifies microbiome alpha diversity, beta diversity or taxanomic abundance.* 9. Determine whether daily administration of up to 67.5 mg insulin modifies peripheral blood T cell or monocyte populations. 10. Determine whether daily administration of up to 67.5 mg insulin modifies plasma inflammatory markers.* 11. Determine whether daily administration of up to 67.5 mg insulin modifies the transcriptome of peripheral blood mononuclear cells.* *These secondary outcomes may be assessed in only the first 90 participants. For all outcomes, analyses will also be stratified by INS genotype and HLA DR4. ;Timepoint(s) of evaluation of this end point: fasting blood glucose test; HbA1c: at baseline, 3 months-, 6 months-, 9 months and 12 months of treatment and during the follo | — |
Countries
Germany
Contacts
Public ContactUniv.-Prof. Dr. Anette-G. Ziegler
Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universsität München
Outcome results
None listed