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J Neurol. 2017 Dec;264(12):2457-2463. doi: 10.1007/s00415-017-8647-0. Epub 2017 Oct 26.

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

Author information

1
Fulbourn Hospital, Fulbourn, Cambridge, CB21 5EF, UK.
2
Addenbrooke's Hospital, Hills Road, Cambridge, CB21 2QQ, UK.
3
Quantitative Biology, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Cambridge, CB4 0WG, UK.
4
UK Dementia Research Institute, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK.
5
Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK.
6
Department of Clinical Neurosciences, and MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0SZ, UK.
7
Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK.
8
Addenbrooke's Hospital, Hills Road, Cambridge, CB21 2QQ, UK. rab46@cam.ac.uk.
9
Department of Clinical Neurosciences, and MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0SZ, UK. rab46@cam.ac.uk.
10
John Van Geest Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK. rab46@cam.ac.uk.

Abstract

Preclinical data have 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. 18 non-demented patients with mild to moderate HD took daily doses of 1 mg Rilmenidine for 6 months and 2 mg for a further 18 months followed by a 3-month washout 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. 12 patients completed the study; reasons for withdrawal included problems tolerating study procedures (MRI, and venepuncture), depression requiring hospital admission and logistical reasons. Three serious adverse events were recorded, including hospitalisation 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 were not made. 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:

Autophagy; Cognition; Interventional trial; MRI; Neurodegenerative disease

PMID:
29075837
PMCID:
PMC5688221
DOI:
10.1007/s00415-017-8647-0
[Indexed for MEDLINE]
Free PMC Article

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