Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001356651p
Ethics application status
Submitted, not yet approved
Date submitted
24/11/2023
Date registered
21/12/2023
Date last updated
21/12/2023
Date data sharing statement initially provided
21/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Pregabalin for the treatment of Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) associated chronic cough.
Scientific title
Feasibility of Pregabalin for the treatment of CANVAS associated chronic cough
Secondary ID [1] 310990 0
nill known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) 332091 0
chronic cough 332092 0
Condition category
Condition code
Neurological 328815 328815 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is divided into a two week Screening Phase, followed by 12 weeks of either placebo or pregabalin (treatment phase one) followed by a four week washout period where no drug/placebo is administered, followed by another 12 week period of either pregabalin or placebo (treatment phase two). At the end of 12 weeks there is a final safety period of four weeks (End Phase) were no drug/placebo is administered but the study team continues to follow the participants.
Participants will receive pregabalin, as an oral capsule at 75 mg twice per day for 12 weeks within a 36 week cross over study. Unused tablets will be returned to dispenser for counting to monitor compliance.
For participants who must reduce their dosage following intolerable adverse drug reaction, they will reduce to one capsule per day. For those who still experience unmanaged cough, they may increase their dosage. This will be increased to three capsules per day if they are tolerating the medication and their blood test results are not deranged. Participants may be offered this increase or decrease of dosage at the end of the first week of each treatment phase. Safety bloods are to be performed at screening, four weeks into treatment phase one and four weeks in treatment phase two. Additional safety bloods may be ordered in the medical opinion of the PI.
Intervention code [1] 327432 0
Treatment: Drugs
Comparator / control treatment
Participants in this study act as their own controls by means of a cross-over study design where participants will receive the intervention; pregabalin and an inactive control (placebo) but at different stages of the study. The control capsule will be made from microcellulose and will have the same appearance and capsule as the drug.
Control group
Placebo

Outcomes
Primary outcome [1] 336620 0
To determine whether pregabalin reduces the frequency of CANVAS associated coughing
Timepoint [1] 336620 0
Cough frequency monitoring will be continuous from screening (Week 0) to the study end (Week 36). At each visit (in person or remote) the researcher will check that the participants are recording their coughs and ensure data capture. The cough frequency is calculated for each phase of the study; Screening/baseline to the start of Phase one (Week 0 - Week 2). Phase one (Week 2 - 12), Washout (Week 12-16), Phase two (Week 16 - 28) and the End Phase (week 28 - 32).
Secondary outcome [1] 429014 0
To determine the tolerability and safety of pregabalin treatment in this population
Timepoint [1] 429014 0
These patient reported measures will be performed at each visit (in person and remote) from screening (Week 0) to the study's closure (Week 36) to capture dynamic change in scores across both screening, treatment one, washout and treatment two. Survey scores are calculated at each phase of the study; Screening/baseline to the start of Phase one (Week 0 - Week 2). Phase one (Week 2 - 12), Washout (Week 12-16), Phase two (Week 16 - 28) and the End Phase (Week 28 - 32). The surveys are performed every 2 Weeks in accordance with the visit schedule from Screening to the end visit (36 Weeks)
Secondary outcome [2] 429015 0
To determine the participant reported effect of pregabalin on the severity of CANVAS associated chronic cough
Timepoint [2] 429015 0
These patient reported measures will be performed at each visit (in person and remote) from screening (Week 0) to the study's closure (Week 36) to capture dynamic change in scores across both screening, treatment one, washout and treatment two. Survey scores are calculated at each phase of the study; Screening/baseline to the start of Phase one (Week 0 - Week 2). Phase one (Week 2 - 12), Washout (Week 12-16), Phase two (Week 16 - 28) and the End Phase (week 28 - 32). The surveys are performed every 2 Weeks in accordance with the visit schedule from Screening to the end visit (36 weeks)

Eligibility
Key inclusion criteria
• Participants with neurological symptoms attributable to RFC1 pathology (neuropathy, vestibular failure, ataxia)
• Positive RFC1 genetic test (either biallelic pathological expansion or pathological expansion and pathological variant).
• > 1 year of chronic cough
• 18 years and over
• Can give informed consent.
• Has access to a smart phone.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of cancer (other than skin squamous cell carcinoma (SSC) or basal cell carcinoma (BCC)).
• History of severe renal impairment (glomerular filtration rate (GFR) < 30)
• History of intolerance to pregabalin
• Pregnancy*/breastfeeding.
• Active respiratory disease.
• Current or recently quit (< 6 months) smokers.
• Angiotensin Converting Enzyme (ACE) inhibitor use.
• Productive cough.
• Use of any pregabalin, gabapentin within 3 months of baseline visit
• Comorbid medical condition which, in the opinion of the Principal Investigator (PI) will either confound the outcome of the study, or place the participant at risk
• Blood test abnormalities at screening indicating severe liver or kidney dysfunction

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)
Allocation concealment will be performed by computer based randomisation performed by a member of the University research group but not the study team.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation sequence will be generated by REDCap database randomisation function.
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
Crossover
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/01/2024
Actual
Date of last participant enrolment
Anticipated
20/03/2024
Actual
Date of last data collection
Anticipated
27/11/2024
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment outside Australia
Country [1] 25975 0
New Zealand
State/province [1] 25975 0

Funding & Sponsors
Funding source category [1] 315254 0
Charities/Societies/Foundations
Name [1] 315254 0
Neurological Foundation of New Zealand
Country [1] 315254 0
New Zealand
Primary sponsor type
Individual
Name
Richard Roxburgh
Address
The University of Auckland, 26-30 Park Av, Grafton, Auckland, 1023
Country
New Zealand
Secondary sponsor category [1] 317286 0
Individual
Name [1] 317286 0
Juno Barnett Collins
Address [1] 317286 0
The University of Auckland, 26-30 Park Av, Grafton, Auckland, 1023
Country [1] 317286 0
New Zealand

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314172 0
Southern Human Disability and Ethics Committee
Ethics committee address [1] 314172 0
Ethics committee country [1] 314172 0
New Zealand
Date submitted for ethics approval [1] 314172 0
24/11/2023
Approval date [1] 314172 0
Ethics approval number [1] 314172 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130670 0
A/Prof Richard Roxburgh
Address 130670 0
The University of Auckland, 26- 30 Park Av, Grafton, Auckland. 1023
Country 130670 0
New Zealand
Phone 130670 0
+64 21774503
Fax 130670 0
Email 130670 0
[email protected]
Contact person for public queries
Name 130671 0
Juno Barnett Collins
Address 130671 0
The University of Auckland, 26 - 30 Park Av, Grafton, Auckland, 1023
Country 130671 0
New Zealand
Phone 130671 0
+64 2102843954
Fax 130671 0
Email 130671 0
[email protected]
Contact person for scientific queries
Name 130672 0
Juno Barnett Collins
Address 130672 0
The University of Auckland, 26 - 30 Park Av, Grafton, Auckland, 1023
Country 130672 0
New Zealand
Phone 130672 0
+64 2102843954
Fax 130672 0
Email 130672 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to the rare nature of CANVAS IPD could deidentify study participants.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20974Study protocol  [email protected] 386903-(Uploaded-20-11-2023-07-55-26)-Study-related document.pdf
20975Informed consent form  [email protected] 386903-(Uploaded-20-11-2023-07-57-03)-Study-related document.pdf



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.