European-Huntington-Disease-Initiative (EHDI)-Study: Effect of riluzole on disease progression

Riluzole has been shown to modify disease progression in amyotrophic lateral sclerosis (ALS) resulting in improved survival rates compared to controls.

First studies in a transgenic mouse model of HD indicated an increase in survival time for these mice under riluzole and a fragmentation of neuronal intranuclear inclusions. Wether riluzole has an effect in HD patients in slowing down the disease progression was studied in the multi-national EHDI trial.

The EHDI study was a phase III multicenter, double-blind, placebo-controlled trial to study the effect of riluzole 50mg b.i.d. for 36 months on the progression of HD. Primary efficacy parameters was the mean change from baseline of the total functional capacity score (TFC) and the mean change from baseline of the motor score (MS) of the UHDRS as well as a combined score (CS) of TFC and MS after treatment with riluzole in comparison to placebo. Because of reports of a possible effect of riluzole on some symptoms of HD, in particular chorea, the effect of riluzole on disease progression is assessed following a washout phase of one month after 36 months of treatment with study medication. HD patients were included between 25 and 65 years of age, carrying a CAG-repeat extension in the HD gene of more than 36, to display clinical signs of HD (defined as a motor score of more than 5) and to be in an early stage of HD (defined as an TFC-score more than 8).

537 HD patients were randomized in 43 centers in 8 countries (France, Germany, Spain, The Netherlands, Italy, Austria, Switzerland, Poland). After three years treatment 366 Hd patients are still on treatment. 171 Hd patients (31.8%) dropped ot due to different reasons, e.g. adverse events, suicide and suicide attempts, start of antichoreic medication, etc.). Results on disease progression will be discussed.

The study was supported by Aventis Pharma, a company of the sanofi-aventis group.