An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington's disease.

Abstract

Objective: Preclinical data has shown that rilmenidine can regulate autophagy in models of Huntington’s disease (HD), providing a potential route to alter the disease course in patients. Consequently, a 2-year open label study examining the tolerability and feasibility of rilmenidine in mild-moderate HD was undertaken.

Methods: 18 non-demented patients with mild to moderate HD took daily doses of 1mg Rilmenidine for six months and 2mg for a further 18 months followed by a 3-month wash out period. The primary outcome was the number of withdrawals and serious adverse events. Secondary outcomes included safety parameters and changes in disease-specific variables such as motor, cognitive and functional performance, structural MRI and serum metabolomic analysis.

Results: 12 patients completed the study; reasons for withdrawal included problems tolerating study procedures (MRI, venepuncture), depression requiring hospital admission and logistical reasons. Three serious adverse events were recorded, including the hospitalization for depression, but none were thought to be drug-related. Changes in secondary outcomes were analysed as the annual rate of change in the study group. The overall change was comparable to changes seen in recent large observational studies in HD patients, though direct statistical comparisons to these studies was not made.

Conclusion. Chronic oral administration of rilmenidine is feasible and well tolerated and future, larger, placebo-controlled, studies in HD are warranted.

Trial registration: EudraCT number 2009-018119-14