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

Phase 2

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Biological: GAD-Alum (Diamyd) 20 µg; Biological: GAD-Alum (Diamyd) 20 µg X 2; Drug: Vitamin D; Drug: Ibuprofen

• Registration Number: NCT01785108
• Lead Sponsor: Johnny Ludvigsson

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2013-02
• Study First Submitted: 2013-02-01
• Study First Submitted QC: 2013-02-04
• Study First Posted: 2013-02-07
• Primary Completion: 2017-03
• Study Completion: 2017-03
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-22
• Last Update Posted: 2017-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GAD-Alum (Diamyd) 20 µg x 2 and Vitamin D	Vitamin D	* 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
GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen	GAD-Alum (Diamyd) 20 µg	* 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
GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen	Ibuprofen	* 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
GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen	Vitamin D	* 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
GAD-Alum (Diamyd) 20µg and Vitamin D	GAD-Alum (Diamyd) 20 µg	* GAD-Alum (Diamyd) 20 µg given twice with one month interval * Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450
Placebo	Vitamin D	-
Placebo	GAD-Alum (Diamyd) 20 µg X 2	-
Placebo	Ibuprofen	-
GAD-Alum (Diamyd) 20 µg x 2 and Vitamin D	GAD-Alum (Diamyd) 20 µg X 2	* 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
GAD-Alum (Diamyd) 20µg and Vitamin D	Vitamin D	* GAD-Alum (Diamyd) 20 µg given twice with one month interval * Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Decrease in inflammatory markers, e.g. TNF-alfa, IL-1 beta, IL-2, IL-17	6, 15 and 30 months
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
Fasting C-peptide, change between baseline and month 6, 15 and 30	6, 15 and 30 months

Trial Locations

Locations (10)

Kalmar Hospital; 🇸🇪 Kalmar, Sweden

Halmstad Hospital; 🇸🇪 Halmstad, Sweden

Astrid Lindgren Children's Hospital - Huddinge; 🇸🇪 Huddinge, Sweden

Linköping University; 🇸🇪 Linköping, Sweden

Skåne University Hospital, UMAS; 🇸🇪 Malmö, Sweden

Lund University Hospital; 🇸🇪 Lund, Sweden

Sachsska, Södersjukhuset; 🇸🇪 Stockholm, Sweden

Astrid Lindgren Children's Hospital; 🇸🇪 Stockholm, Sweden

Uddevalla Hospital; 🇸🇪 Uddevalla, Sweden

Örebro University Hospital; 🇸🇪 Örebro, Sweden