diabetes mellitus type 1 Type 1 diabetes
Conditions
Interventions
The 21 participants in the treatment group will receive a three-day intravenous
methylprednisolone 1000mg course followed by 12 weeks prednisolone in a taper
dose, combined with diazoxide 2dd 200mg
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
12 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Age 16 - 40 years • Diagnosis of type 1 diabetes in the last eight weeks • Presence of β-cell autoantibodies (eligible autoantibodies: anti-GAD and anti-IA-2) • Of Caucasian ethnicity • Mixed meal test stimulated C-peptide AUC0-120min >0.2 nmol/L
Exclusion criteria
Exclusion criteria: • Unmanageable metabolic instability (ketoacidosis) • Current use of other immunosuppressive or immunomodulatory therapy • Current acute infection • Current parasitic infections • Heart failure • Hyperuricemia • History of malignancy • (Possible) previous tuberculosis infection • Active ulcus ventriculi or duodeni • Use of CYP3A4 inhibitors of inducers • Known hypersensitivity or intolerability to one of the investigational products • Female patients who are pregnant or breastfeeding • Female patients who are fertile and unwilling to use adequate contraception during the 12 month study period • Recent patient*s involvement in other studies which in the opinion of the investigators could affect the safety of the patient or the result of the study • Any condition which, in the opinion of the Investigator might jeopardise the subject*s safety or compliance with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The difference of the 2 hour MMTT mean C-peptide AUC between the treatment and placebo group after 24 months. The MMTT is also performed at baseline, 17 days, 6 weeks, 14 weeks, 12 months and at 24 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| • The proinsulin and glucose concentration before and during the MMTT at baseline, 2 weeks, 6 weeks, 14 weeks, 26 weeks, 12 months and 24 months. • Insulin use (assessed as the average IU/kg/day during the last week) and HbA1c at baseline, 6 weeks, 14 weeks, 26 weeks, 28 months, 12 months and 24 months. • Time spent with interstitial glucose in hypoglycemic range (10.0), standard deviation, coefficient of variance and mean amplitude of glucose excursions (MAGE), as determined by open continuous glucose measurement (CGM) during the treatment period and a blinded CGM at 12 and 24 months • General and diabetes specific quality of life, diabetes self-management, hypoglycaemic distress and hyperglycaemic distress assessed by questionnaire at baseline, after 14 weeks, 8, 12 months and 24 months. • Occurrence of adverse events and severe adverse events (specifically infections) • Pancreas inflammation as determined by FDG-PET scan, before and 3 months after methylprednisolone or placebo • Effect on β-cell auto-immunity and β-cell stress measured by o Number of immune cells determined by FACS analysis o T cell responsiveness to diabetes specific antigens (including Insulin-defective ribosomal products (DRiPs)) as determined by LST, compared to other antigens o Number of CD8+ autoreactive T cells as determined by tetramer using the Q-DOT assay o Level or quality of beta-cell autoantibodies (eligible autoantibodies: anti GADA or IA-2A) by commercial ELISA. | — |
Countries
Netherlands
Outcome results
None listed