Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001611415
Ethics application status
Approved
Date submitted
31/10/2016
Date registered
22/11/2016
Date last updated
22/11/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomized trial of varenicline (Champix) for the treatment of cognitive and affective symptoms in Huntington's Disease
Scientific title
A randomized trial of varenicline (Champix) for the treatment of cognitive and affective symptoms in Huntington's Disease
Secondary ID [1] 285776 0
None
Universal Trial Number (UTN)
U1111-1163-7565
Trial acronym
VCAS-HD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington's Disease 293659 0
Condition category
Condition code
Neurological 293957 293957 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 296264 0
Treatment: Other
Comparator / control treatment
Placebo capsules contain methylcellulose
Control group
Placebo

Outcomes
Primary outcome [1] 300017 0
Functional performance (UHDRS)
Timepoint [1] 300017 0
Functional performance (UHDRS) is assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [1] 328813 0
Anxiety assessed by Hospital Anxiety and Depression scale
Timepoint [1] 328813 0
Assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [2] 329347 0
Irritability assessed by the Irritability questionnaire (IRQ)
Timepoint [2] 329347 0
Assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [3] 329349 0
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.
Timepoint [3] 329349 0
FIBSER performed at day 0 (baseline), days 3, 7, weeks 2, 3, 4, 8, 12 , 14 and 16
Secondary outcome [4] 329464 0
Cognitive testing (primary outcome). Task 1: motor tapping (hand-eye coordination and manual dexterity),
Timepoint [4] 329464 0
Assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [5] 329465 0
Cognitive testing (primary outcome). Task 2: verbal interference (inhibition of unwanted, well-learned impulsive automatic responses),
Timepoint [5] 329465 0
Cognitive function is assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [6] 329466 0
Cognitive testing (primary outcome). Task 3: Go-No-Go (impulsivity and attention),
Timepoint [6] 329466 0
Cognitive function is assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [7] 329469 0
Cognitive testing (primary outcome). Task 4: emotional recognition and recall (basic emotion recognition and discrimination),
Timepoint [7] 329469 0
Cognitive function is assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [8] 329470 0
Cognitive testing (primary outcome). Task 5: Switching attention (visuomotor tracking, simple attention).
Timepoint [8] 329470 0
Cognitive function is assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [9] 329471 0
Cognitive testing (primary outcome). Task 6: Executive maze (planning, abstraction, foresight, error correction),
Timepoint [9] 329471 0
Cognitive function is assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).
Secondary outcome [10] 329472 0
Cognitive testing (primary outcome). Task 7: Spot the Real Word (language comprehension and estimation of premorbid intelligence quotient).
Timepoint [10] 329472 0
Cognitive function is assessed at baseline (visit1) and then again in the final week of treatment (week 12, visit 2). Participants are again assessed 4 weeks after treatment ends (week 16, visit3). This study design allows investigation of efficacy (visit 2 vs baseline) and whether effects persist during washout (visit 3 vs visit 2).

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Due to the relatively small sample population, randomisation will be balanced for age and gender and stratified based on baseline UHDRS scores. The allocation of each participant will be noted in individual sealed envelopes and stored in the TMF
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomisation of participants to groups at the baseline visit according to the computer generated list
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Baseline comparability of the intervention and control group will be assessed by descriptive analyses of the baseline information collected.
The mean scores and standard deviations together with the total score for each of the cognitive tasks, subscales of UHDRS, HADS and IRQ scores will be reported at every visit they are collected.
The change from baseline to visit2 and visit3 in each of the primary and secondary outcomes, between the treated and control group will be analysed using mixed model regression. If baseline characteristics are found to be substantially different between the groups, these will be adjusted for in the regression modelling. The primary and secondary main analyses will be conducted on an intention-to-treat (ITT) basis. All statistical analyses will be unadjusted except where indicated.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
11/11/2015
Date of last participant enrolment
Anticipated
31/10/2017
Actual
Date of last data collection
Anticipated
23/01/2018
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 8360 0
New Zealand
State/province [1] 8360 0
Auckland

Funding & Sponsors
Funding source category [1] 294826 0
Charities/Societies/Foundations
Name [1] 294826 0
Oakley Mental Health Research Foundation
Country [1] 294826 0
New Zealand
Funding source category [2] 294827 0
Charities/Societies/Foundations
Name [2] 294827 0
New Zealand Pharmacy Education and Research Foundation
Country [2] 294827 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Park Road
Grafton
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 293670 0
None
Name [1] 293670 0
None
Address [1] 293670 0
None
Country [1] 293670 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296216 0
HDEC
Ethics committee address [1] 296216 0
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 296216 0
New Zealand
Date submitted for ethics approval [1] 296216 0
23/03/2015
Approval date [1] 296216 0
22/04/2015
Ethics approval number [1] 296216 0
15/STH/19

Summary
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.
Trial website
None
Trial related presentations / publications
McGregor AL, Dysart J, Tingle MD, Russell BR, Kydd RR, Finucane G
Varenicline improves motor and cognitive symptoms in early Huntington's disease
Neuropsychiatric Disease and Treatment (2016); 12: 2381–2386




Public notes

Contacts
Principal investigator
Name 53222 0
Dr Ailsa McGregor
Address 53222 0
School of Pharmacy
University of Otago
PO Box 56
Dunedin 9054
Country 53222 0
New Zealand
Phone 53222 0
+64 3 479 4235
Fax 53222 0
Email 53222 0
[email protected]
Contact person for public queries
Name 53223 0
Dr Ailsa McGregor
Address 53223 0
School of Pharmacy
University of Otago
PO Box 56
Dunedin 9054
Country 53223 0
New Zealand
Phone 53223 0
+64 3 479 4235
Fax 53223 0
Email 53223 0
[email protected]
Contact person for scientific queries
Name 53224 0
Dr Ailsa McGregor
Address 53224 0
School of Pharmacy
University of Otago
PO Box 56
Dunedin 9054
Country 53224 0
New Zealand
Phone 53224 0
+64 3 479 4235
Fax 53224 0
Email 53224 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseClinical Trials Corner: September 2017.2017https://dx.doi.org/10.3233/JHD-170262
N.B. These documents automatically identified may not have been verified by the study sponsor.