A randomized trial of varenicline (Champix) for the treatment of cognitive and affective symptoms in Huntington's Disease

INTERVENTION: 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. CONDITION: Huntington's Disease PRIMARY OUTCOME: Functional performance (UHDRS) SECONDARY OUTCOME: Anxiety assessed by Hospital Anxiety and Depression scale Cognitive testing (primary outcome). Task 3: Go‐No‐Go (impulsivity and attention), Cognitive testing (primary outcome). Task 1: motor tapping (hand‐eye coordination and manual dexterity), Cognitive testing (primary outcome). Task 2: verbal interference (inhibition of unwanted, well‐learned impulsive automatic responses), Cognitive testing (primary outcome). Task 4: emotional recognition and recall (basic emotion recognition and discrimination), Cognitive testing (primary outcome). Task 5: Switching attention (visuomotor tracking, simple attention). Cognitive testing (primary outcome). Task 6: Executive maze (planning, abstraction, foresight, error correction), Cognitive testing (primary outcome). Task 7: Spot the Real Word (language comprehension and estimation of premorbid intelligence quotient). Irritability assessed by the Irritability questionnaire (IRQ) The frequency, intensity and burden of any reported side effects will be recorded using a standard FIBSER scale at clinic visits and at follow up telephone calls. 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.