Efficacy of Diazoxide in Type 1 Diabetes
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Efficacy of 6 Months Treatment With Diazoxide at Bedtime in Preventing Beta-cell Demise in Newly Diagnosed Type 1 Diabetes|
- Insulin secretion (measured by fasting and stimulated c-peptide) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Glycemic control (measured by blood glucose) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Autoimmune activity (measured by islet antibodies) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Side effects [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2005|
|Study Completion Date:||August 2008|
|Primary Completion Date:||August 2008 (Final data collection date for primary outcome measure)|
At the time of diagnosis most subjects with type 1 diabetes retain significant endogenous insulin secretion as assessed by C-peptide measurements. Although not sufficient for the needs of the individual, residual insulin secretion is important for metabolic control, for avoidance of hypoglycemic episodes and, perhaps, for protection against diabetic complications. To retain residual endogenous insulin secretion in type 1 diabetes is thus highly desirable.
Residual insulin secretion deteriorates during the course of type 1 diabetes. The underlying autoimmune process is a major determinant of deterioration.
However, also measures that do not directly target the immune system could be beneficial. The DCCT study randomised subjects with type 1 diabetes to either intensive or conventional insulin treatment. The intensive insulin treatment markedly retarded deterioration in C-peptide levels during 5 years of observation. The favourable effect could be due to lesser hyperglycemia per se. Alternatively, the effect of intensive insulin treatment could be secondary to lesser degree of over-stimulation of the patients' beta-cells.
It is by now established that relief from over-stimulation by diazoxide favourably affects beta-cell function and that such treatment can retard a decline in residual insulin secretion in subjects with newly diagnosed type 1 diabetes. Diazoxide has been used in clinical practice for > three decades without major safety concerns.
Disturbing, albeit reversible, side effects are halting long-term studies with diazoxide in type 1 diabetes. The researchers find that lower and intermittent (i.e. night time) dosing of diazoxide produces no measurable side effects in subjects with type 2 diabetes.
This is a double blinded placebo controlled study, with 35 participants with newly diagnosed type 1 diabetes are randomised into either placebo or Diazoxide for 6 months. The patients will be followed up after intervention for at least 12 months.
Beta cell function and glycemic control will be monitored.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00131755
|University Hospital of Trondheim|
|Trondheim, Norway, 7006|
|Principal Investigator:||Grill Valdemar, MD PhD||Norwegian University of Science and Technology|