None listed
Conditions
Brief summary
Huntington’s Disease (HD) is a fatal, inherited neurodegenerative disorder affecting 1:10,000 people in New Zealand. HD is characterized by disorders of movement, cognition, behaviour, and functional capacity. At present there is no clinical treatment to prevent or reduce the onset or progression of HD. It remains unclear which particular disease mechanisms are important in HD. Post mortem and genetic mouse model studies suggest that impaired cholinergic neurotransmission, through a loss of agonist (acetylcholine) rather than nicotinic receptors may be a significant contributing factor to HD pathology. These observations present a provocative argument that administration of an exogenous agonist may be an effective therapeutic strategy for HD. The aim of this project is to investigate whether treatment with the nicotine analogue varenicline (Champix) which is currently approved for smoking cessation, can improve cognitive and psychiatric symptoms in patients with mid-late stage HD. We will undertake a double blind, placebo controlled, randomised study of varenicline (Champix, 1mg twice daily) in patients with Huntington’s disease (HD). Specifically this study will determine whether treatment with varenicline for 12 weeks (1mg twice daily) 1. Improves patients’ motor function and total functional capacity 2. Improves cognitive performance in computer based tasks which assess learning and memory, attention, impulsiveness and emotional recognition 3. Improves patients’ mood and reduces anxiety and irritability The primary outcomes measure to determine the efficacy of varenicline will be functional outcome and performance in the neurocognitive test battery. Secondary outcome measures will be hospital anxiety and depression (HADS) and irritability (IRQ) clinical rating scales.
Interventions
This study is a double-blind, placebo-controlled, randomised trial of varenicline using the standard dosing regimen for smoking cessation (Champix, starting dose 0.5mg/day escalating to 2mg/day) in patients with Huntington’s disease (HD).
Bulk study medication will be contained in opaque gel capsules and repackaged into identical compliance packaging by an independent pharmacy according to the randomisation schedule. Sealed envelopes containing the treatment assignment for each subject will be
This study is a double-blind, placebo-controlled, randomised trial of varenicline using the standard dosing regimen for smoking cessation (Champix, starting dose 0.5mg/day escalating to 2mg/day) in patients with Huntington’s disease (HD). Bulk study medication will be contained in opaque gel capsules and repackaged into identical compliance packaging by an independent pharmacy according to the randomisation schedule. Sealed envelopes containing the treatment assignment for each subject will be held by a member of the study team who is not involved in patient assessment in case emergency unblinding is required. Study medication will be initiated at a dose of 0.5 mg daily for 3 days, increased to 0.5 mg twice daily on days 4-7, and then increased to 2 mg/day on week 2 (the standard anti-smoking regimen). If adverse events are noted, patients will be permitted to down-titrate by one dose level, which will then be considered their maximal dose. Patients will be maintained at the maximal dose of study medication for 10 weeks. Varenicline and placebo will be stored at room temperature in the locked stores within the School of Pharmacy. The School of Pharmacy holds the appropriate licenses to store these medications. Compliance for this trial will be defined as 80% of doses taken. Participants will be asked to bring blister packaging from used medication to each subsequent visit in order to assess doses taken.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 years to 65 years. 2. Non-smoker 3. Outpatients with Huntington’s Disease diagnosed by a movement disorder specialist 4. Unified Huntington’s Disease Rating Scale (UHDRS) Score between 15-30 5. Ability to ambulate without assistance. 6. Stable dose of current regular medication for the management of HD symptoms for at least 30 days prior to trial entry and for the duration of the trial.
Exclusion criteria
1. Legal incapacity or limited legal capacity 2. Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. 3. Significant renal or hepatic impairment. 4. Participant with life expectancy of less than 6 months, or who is inappropriate for placebo medication. 5. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. 6. Participants who have participated in another research trial involving an investigational product in the past 12 weeks. 7. Patients with a history of substance abuse. 8. Concurrent treatment with any MAOIs, Wellbutrin, antiretroviral medications, immunosupressants, cancer chemotherapy, nicotine patches or nicotine delivery products such as e-cigarettes. 9. Dementia or other psychiatric illness at a level that, in the opinion of the clinician, prevents the patient from giving informed consent (Mini Mental Status Exam score less than 34 and, Addenbrooks Cognitive Examination-Revised (ACE-R) score <65). 10. Presence of psychosis, bipolar disorder, untreated depression (BDI greater than or equal to 21).
Outcome results
None listed