Diabetes Prevention - Immune Tolerance (DIAPREV-IT)
A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies
Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet diabetes.
DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset of type 1 diabetes.
The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes.
The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.
50 children will be randomized to 2 injections of Diamyd® or placebo. In DIAPREV-IT we will use the previously tested dose of 20 µg Diamyd® administered as a prime-and-boost at days 1 and 30, as no serious adverse reactions have been observed with this regimen. The children will be followed every 3rd month for 5 years. Before the first injection of study drug both intravenous (IvGTT) and oral (OGTT)glucose tolerance test will be performed. These will be repeated during the study with OGTT every 6 month visit and IvGTT every full year visit.
The proportion of subjects in the two treatment groups who develop type 1 diabetes after 3, 4 and 5 years of follow up.
Change in first-phase insulin response on IvGTT from baseline Fasting and 2 hours C-peptide levels on OGTT Two hour glucose value after OGTT Change in HbA1c from baseline
Children developing diabetes in the study will be offered to participate in a postdiagnosis protocol. Children who have had two doses of active Diamyd in the main study will be given one additional dose of 20 microgram Diamyd followed by one dose of placebo after 30 days. Children who have had two doses of placebo will be given two doses of 20 microgram Diamyd with 30 days in between. Post diagnosis follow up will proceed for at least 15 months from the first post diagnosis injection with collection of adverse events and metabolic evaluation with Mixed meal tolerance tests.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
|Official Title:||A Double-blind, Randomized Investigator-initiated Study to Determine the Safety and the Effect of Diamyd® on the Progression to Type 1 Diabetes in Children With Multiple Islet Cell Autoantibodies|
- diabetes [ Time Frame: After 3, 4 and 5 years from inclusion in the study ] [ Designated as safety issue: No ]Onset of Type 1 diabetes, defined according to ADA criteria, in the placebo group and the group with active substance (Diamyd)
- change in first-phase insulin response [ Time Frame: After 3, 4 and 5 years of inclusion in the study ] [ Designated as safety issue: No ]As secondary variables of effect we will measure the change in first-phase insulin response. In all children a baseline IvGTT is performed and after that annual IvGTT´s are performed within the study. First phase insulin response is calculated from insulin 1 and 3 minutes after the given glucose solution. Insulin is measured by Laboratory of Clinical Chemistry at Skåne University Hospital, Malmö. Change in first phase insulin response will be calculated for each individual and compared between the groups.
- Glucose levels [ Time Frame: Change in fasting glucose after 3, 4 and 5 years of participation in the study ] [ Designated as safety issue: No ]Fasting glucose is measured at baseline and every 6 months within the study. 2 hour glucose at OGTT is analysed at baseline and annually in the study. Change in fasting glucose and 2 hour glucose will be analysed in all participants and compared within the groups. Glucose is analysed by Hemocue.
- c-peptide levels [ Time Frame: After 3, 4 and 5 yearsof participation in the study ] [ Designated as safety issue: No ]
Fasting and 2 hours C-peptide levels on OGTT will be analysed at baseline and att OGTT´s performed anually within the study.The change in levels will be analysed in each participants and compared between groups.
C-peptide is analysed at laboratory of Clinical Chemistry Skåne University Hospital, Malmö
- HbA1c [ Time Frame: After 3, 4 and 5 years of participation in the study ] [ Designated as safety issue: No ]
At all visits in the study HbA1c is measured. The change in HbA1c from baseline in each individual will be analysed and compared between the groups.
HbA1c is analysed at Laboratory of Clinical Chemistry, Skåne University Hospital, Malmö
|Study Start Date:||April 2009|
|Estimated Study Completion Date:||January 2017|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo comparator||
Other: Placebo comparator
Placebo comparator day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: Two doses of 20 microgram Diamyd day 1 and 30 in children originally receiving placebo.
Other Name: Alum-GAD
Active Comparator: Diamyd®
20 microgram day 1 and 30
20 microgram day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: One dose of Diamyd followed by one dose of placebo to children originally receiving Diamyd
Other Name: Alum-GAD
|Clinical Research Center, Pediatric Endocrinology, Ing 72, hus 91, plan 10|
|Malmö, Sweden, 205 02|
|Principal Investigator:||Helena Elding Larsson, MD, PhD||Region Skåne and Lund University|