The European Nicotinamide Diabetes Intervention Trial (ENDIT) is a multinational placebocontrolled intervention study aiming at establishing the utility of nicotinamide in preventing or delaying the clinical presentation of insulin-dependent diabetes mellitus (IDDM) in individuals at increased risk of contracting the disease.
Nicotinamide is a water soluble group B vitamin which has been shown to be effective in preventing onset of diabetes in animal models, has produced promising results in uncontrolled trials in non-diabetic relatives with high levels of islet cell antibodies (ICA), and may have some benefit in prolonging beta cell function in recently diagnosed patients with insulin-dependent diabetes.
No serious side effects have been reported from its use at the doses proposed in man or other species.
The trial will be undertaken on a European multinational basis. Relatives of patients developing diabetes under the age of 21 will be screened for islet cell antibodies.
Those with confirmed levels 2 20 JDF units and meeting the age criteria will be asked to undergo both oral and intravenous glucose tolerance tests and will be invited to take part in a prospective randomized placebo controlled trial of nicotinamide vs placebo.
A total of 422 subjects will require up to 5 years of treatment to demonstrate or exclude any clinically useful benefit of nicotinamide (ie a 90% power to identify an overall 40% reduction in risk of progression to diabetes over the study period, and a 25% risk reduction in the sub-group at highest risk).
Active participation by the Eastern European groups involved in this proposal has made it possible to extend the size and power of the trial by extending screening from 22000 to 26000 first degree relatives, and thus to reduce the risk of missing a clinically useful effect of the drug. This, the first major European study to attempt intervention in the prodromal phase of childhood diabetes, has already attracted support from well established centres with a sufficiently large screening population to ensure rapid recruitment of the large numbers needed for such and endeavour.