An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington's disease.
View / Open Files
Authors
Underwood, Benjamin R
Green-Thompson, Zeyn W
Pugh, Peter J
Lazic, Stanley E
Publication Date
2017-12Journal Title
Journal of neurology
ISSN
0340-5354
Publisher
Dietrich Steinkopff Verlag
Volume
264
Issue
12
Pages
2457-2463
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Underwood, B. R., Green-Thompson, Z. W., Pugh, P. J., Lazic, S. E., Mason, S., Griffin, J., Jones, S., et al. (2017). An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington's disease.. Journal of neurology, 264 (12), 2457-2463. https://doi.org/10.1007/s00415-017-8647-0
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
Keywords
Brain, Humans, Huntington Disease, Oxazoles, Adrenergic alpha-Agonists, Magnetic Resonance Imaging, Treatment Outcome, Retrospective Studies, Longitudinal Studies, Neuropsychological Tests, Time Factors, Adolescent, Adult, Aged, Middle Aged, Female, Male, Metabolomics, Young Adult, Rilmenidine
Sponsorship
This work was supported by an NIHR grant of a Biomedical Research Centre to the University of Cambridge/ Addenbrookes Hospital, Wellcome Trust (Principal Research Fellowship to DCR (095317/Z/11/Z) and JBR (Senior Research Fellowship, 103838) and DCR is grateful for funding from the UK Dementia Research Institute (funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society). In addition the imaging part of the study was supported by a grant from the Rosetrees Trust
Funder references
WELLCOME TRUST (103838/Z/14/Z)
MRC (MR/P011705/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Wellcome Trust (095317/Z/11/Z)
MRC (MC_PC_12012)
Medical Research Council (MC_U105597119)
Medical Research Council (MC_PC_13030)
Identifiers
External DOI: https://doi.org/10.1007/s00415-017-8647-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276408
Recommended or similar items
The following licence files are associated with this item: