Читать книгу Clinical Dilemmas in Diabetes - Группа авторов - Страница 45

The ENDIT study, conducted predominantly in Europe, examined whether nicotinamide could lead to a reduction in the rate of progression to T1D in at risk relatives of T1D probands. Over 40,000 first‐degree relatives aged 5–40 years were screened in centers in Europe and North America. The study was designed to recruit at least 422 subjects with ICA titers ≥ 20 JDF units to be randomized to either a nicotinamide‐ or a placebo‐treated group. With an expected rate of progression to diabetes of 40% in the placebo arm, the proposed 5‐year observation period should have allowed a 90% power to observe a 35% reduction in the incidence of disease [26, 27].

Nicotinamide treatment at the doses used did not show any significant effect on the primary outcome – progression to T1D. A total of 159 participants developed the disease within 5 years of randomization to treatment, 82 (30%) in the active treatment group and 77 (28%) in the placebo group. The unadjusted Cox proportional hazard estimate showed no difference between the placebo and nicotinamide groups on an intention to treat basis. Nor was any difference was found between groups after adjustment for age at baseline, glucose concentrations at 2‐h glucose in the OGTT, and number of islet autoantibodies. The proportion of relatives who developed diabetes within 5 years was almost identical in those treated with nicotinamide and those treated with placebo, and there was no suggestion of a treatment effect in any of the subgroups defined by well established markers of additional risk.

A useful message of this trial has been that large‐scale collaborations were essential to move things forward and that the place for single‐center trials was limited.