Diabetes Virus Detection Project, Intervention With GAD-alum

Study Overview
=================
Brief Summary
-----------------
The purposes of this study are to test whether GAD vaccination can stop the progression of newly diagnosed type 1 diabetes, to describe the related immunological processes (insulitis) in pancreas and small intestines evolving the mechanism of the effect of GAD vaccination and finally try to detect viruses and virus receptors directly in the insulin producing beta cells of the pancreas in patients with newly diagnosed type-1 diabetes mellitus (T1D).

Detailed Description
-----------------
The aetiology of type 1 diabetes is unknown. Both genetic and environmental factors seem to be important for the destruction of insulin producing beta cells in the pancreas. Increasing indirect evidences exist that picornaviruses may either directly or indirectly through autoimmune processes destroy beta cells. New sensitive assays have been developed to detect these viruses and to study the immunological processes, especially T-cell function. Microsurgical technology has been refined, now making pancreatic biopsies a safe procedure. This study focuses on advanced in depth studies of immunology and virology in pancreatic tissue and small intestine at an early stage of disease.

Official Title
-----------------
A Phase II-study (Therapeutic Exploratory) of GAD-alum in Newly Diagnosed Type-1 Diabetic Patients, With Focus One the Presence of Viruses at the Time of Diagnosis

Conditions
-----------------
Diabetes, Type I, Enterovirus Infections, Autoimmunity

Intervention / Treatment
-----------------
* Drug: GAD-alum
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly diagnosed classical type-1 diabetes Positive GAD antibodies Fasting C-peptide >0.1 mmol/l Insulin dosage >0.1 U/kg Bodyweight/day Exclusion Criteria: Pregnancy Weaning Other chronic diseases than diabetes Any regular medication except oral contraceptives Psychiatric disturbances

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GAD-alum<br>GAD-alum administered at 0 and 1 months after inclusion | Drug: GAD-alum<br>* 20 µg of GAD-alum injected sc after the biopsy, and repeated after one month<br>* Other names: Diamyd;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo injected after the biopsy and repeated after one month (similar to the GAD-alum-arm)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of insulitis in proportion to living, insulin-staining beta cells in pancreatic biopsies |  | 18 months after inclusion | 
| Prevalence of virus infected islets in pancreatic biopsies |  | 18 months after inclusion | 
| Intensity of insulitis in proportion to living, insulin-staining beta cells in pancreatic biopsies |  | 2 weeks after inclusion | 
| Prevalence of virus infected islets in pancreatic biopsies |  | 2 weeks after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual insulin secretion (C-peptide) measured by Mixed Meal Tolerance Test | Will be measured at 0, 1, 3, 9, 18, 24 and 36 months after diagnosis, but time frame is at 36 months | 36 months after diagnosis | 
| Insulin dosage/kilo bodyweight/24 hours | Will be calculated at 0, 1, 3, 9, 18, 24 and 36 months after diagnosis, but time frame is 36 months after diagnosis | 36 months after diagnosis | 
| Glycosylated hemoglobin A1 (HbA1c) | Will be measrured at 0, 1, 3, 9, 18, 24 and 36 months after diagnosis, but time frame is at 36 months. To investigate wether an eventual better endogenous insulin production gives better metabolic control, estimated by lower HbAic | 36 months after diagnosis | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
insulin