Diabetes, Type I, Enterovirus Infections, Autoimmunity
Conditions
Keywords
insulin
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.
Interventions
DRUGGAD-alum
20 µg of GAD-alum injected sc after the biopsy, and repeated after one month
OTHERPlacebo
Placebo injected after the biopsy and repeated after one month (similar to the GAD-alum-arm)
Sponsors
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Residual insulin secretion (C-peptide) measured by Mixed Meal Tolerance Test | 36 months after diagnosis | Will be measured at 0, 1, 3, 9, 18, 24 and 36 months after diagnosis, but time frame is at 36 months |
| Insulin dosage/kilo bodyweight/24 hours | 36 months after diagnosis | Will be calculated at 0, 1, 3, 9, 18, 24 and 36 months after diagnosis, but time frame is 36 months after diagnosis |
| Glycosylated hemoglobin A1 (HbA1c) | 36 months after diagnosis | 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 |
Countries
Norway
Outcome results
None listed