DIABGAD - Trial to Preserve Insulin Secretion in Type 1 Diabetes Using GAD-Alum (Diamyd) in Combination With Vitamin D and Ibuprofen

Study Overview
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Brief Summary
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The objectives of this study is to evaluate the safety and influence of treatment with GAD-Alum (Diamyd) combined with Vitamin D and Ibuprofen on preservation of residual insulin secretion in recently diagnosed Type 1 Diabetes evaluate how the above mentioned treatments influence the immune system of the subjects and interact with any viral infections evaluate the safety and influence of treatment with double dose of GAD-Alum (Diamyd) plus Vitamin D on the immune system, viral infections, and on preservation of residual insulin secretion in recently diagnosed Type 1 Diabetes

Official Title
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Pilot Trial to Preserve Residual Insulin Secretion in Children and Adolescents With Recent Onset Type 1 Diabetes by Using GAD-antigen (Diamyd) Therapy in Combination With Vitamin D and Ibuprofen

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Biological: GAD-Alum (Diamyd) 20 µg
* Biological: GAD-Alum (Diamyd) 20 µg X 2
* Drug: Vitamin D
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Male and female patients between 10 and 18 years of age Insulin dependent Type 1 Diabetes mellitus diagnosed within the previous 4 months at time of screening Fasting C-peptide level at time of screening above or equal to 0.12 nmol/L Elevated GAD65 antibodies (GADA) at time of screening Main Exclusion Criteria: Treatment with immunosuppressants, continuous anti-inflammatory drug, Vitamin D or any anti-diabetic medications other than insulin A history of certain diseases or conditions (e.g. anemia, HIV, epilepsy, head trauma, neurological diseases or cerebrovascular accident, alcohol or drug abuse etc) Treatment with any vaccine within 4 months prior to first planned administration of GAD-Alum/placebo or planned treatment with vaccine up to 4 months after the last injections with GAD-Alum/Placebo, including influenza vaccines Participation in other clinical trials with a new chemical entity within the previous 3 months Pregnancy or planned pregnancy within 1 year after the last GAD-Alum/placebo dose Presence of associated serious disease or condition which in the opinion of the investigator makes the patient non-eligible for the study

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen<br>GAD-Alum (Diamyd) 20 µg given twice with one month interval Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450 Ibuprofen, 400 mg/day, from Day 1 to Day 90 | Biological: GAD-Alum (Diamyd) 20 µg<br> <br> Drug: Vitamin D<br> <br> Drug: Ibuprofen<br> <br> |
| Active Comparator: GAD-Alum (Diamyd) 20µg and Vitamin D<br>GAD-Alum (Diamyd) 20 µg given twice with one month interval Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450 | Biological: GAD-Alum (Diamyd) 20 µg<br> <br> Drug: Vitamin D<br> <br> |
| Active Comparator: GAD-Alum (Diamyd) 20 µg x 2 and Vitamin D<br>GAD-Alum (Diamyd) 20 µg X 2 given twice with one month interval Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450 | Biological: GAD-Alum (Diamyd) 20 µg X 2<br> <br> Drug: Vitamin D<br> <br> |
| Placebo Comparator: Placebo<br> | Biological: GAD-Alum (Diamyd) 20 µg X 2<br> <br> Drug: Vitamin D<br> <br> Drug: Ibuprofen<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in C-peptide (90 minute value and AUC mean 0-120 min) during a Mixed Meal Tolerance Test from baseline to month 6, 15 and 30 |  | 6 months, 15 months and 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L |  | 6, 15 and 30 months | 
| Hemoglobin A1c (HbA1c), change between baseline and subsequent visits |  | 6, 15 and 30 months | 
| Exogenous insulin dose per kg body weight and 24 hours, change between baseline and subsequent visits |  | 6, 15 and 30 months | 
| Th2-deviation of cell-mediated immune response seen, e.g. as increased ratio of IL-5, 10, 13 in comparison with IFN-gamma, TNF-alfa, IL-1 beta, IL-17, and increase of T-regulatory cells |  | 6, 15 and 30 months | 
| Decrease in inflammatory markers, e.g. TNF-alfa, IL-1 beta, IL-2, IL-17 |  | 6, 15 and 30 months | 
| Fasting C-peptide, change between baseline and month 6, 15 and 30 |  | 6, 15 and 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes type 1, Diamyd, Diabetes, Juvenile Diabetes, Autoimmune Diabetes, Insulin dependent Diabetes, Type 1 diabetes, Type 1 diabetes mellitus, rhGAD65, GAD, GAD65, GAD-alum, Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Vitamin D, Ibuprofen