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Trial registered on ANZCTR


Registration number
ACTRN12619001779167p
Ethics application status
Not yet submitted
Date submitted
2/12/2019
Date registered
16/12/2019
Date last updated
16/12/2019
Date data sharing statement initially provided
16/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating a new target for treatment in Prader-Willi syndrome
Scientific title
Using acamprosate to investigate a new target for treatment in Prader-Willi Syndrome
Secondary ID [1] 299917 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prader-Willi Syndrome 315346 0
Condition category
Condition code
Human Genetics and Inherited Disorders 313648 313648 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-site, open-label, case-controlled trial of acamprosate in 15 individuals with Prader-Willi syndrome (PWS) and 15 typically developing controls.
All participants will be exposed to the investigational product Acamprosate Calcium (Campral). Acamprosate will be delivered orally, via Campral tablets containing 333mg of acamprosate calcium as the active ingredient.

Dosage will be in accordance to the TGA approved schedule, and a daily dose will be calculated according to body weight:
For adults weighing 60 kg or more, the dose is 2 x 333mg tablets, taken three times daily (2 tablets in the morning, at midday and at night).
For adults weighing less than 60 Kg, the dose is 2 x 333mg tablets in the morning, 1 x 333mg tablet at midday and 1 x 333mg tablet at night.

Participants will take the recommended dosage for 7 days, and keep a medication log to record the time they take the medication during the day.
Intervention code [1] 316191 0
Treatment: Drugs
Comparator / control treatment
As this is a case-controlled trial of acamprosate, the control group will be made up of typically developing adults who will also receive the investigational product Acamprosate Calcium (Campral).
Control group
Active

Outcomes
Primary outcome [1] 322083 0
Brain GABA levels will be assessed by E-I flux on magnetic resonance spectroscopy
Timepoint [1] 322083 0
At 7 days after commencing treatment.
Secondary outcome [1] 377273 0
Re-established brain connectivity as measured by FMRI
Timepoint [1] 377273 0
At 7 days after commencing treatment

Eligibility
Key inclusion criteria
1. Aged between 18 to 30 years.
2. For participants with PWS, a confirmed genetic diagnosis of PWS.
3. Provide voluntary, written informed consent (all participants). For participants with PWS, parent / legal guardian also provides voluntary, written consent.
Minimum age
18 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Aged 17 years or younger and 31 years or older.
2. MRI contraindications (e.g. pregnant, metal in the body, insulin pumps, vertigo, claustrophobia, etc)
3. For PWS participants, comorbid psychiatric or neurological disorder that is not associated with PWS
4. For controls, no known neurological, psychiatric, neurogenetic or serious medical condition
5. Currently receiving treatment with a GABA compound
6. For non-GABA compounds, concomitant drug use will be allowed as long as there has been stable dosing for at least 4 weeks prior to participation
7. If evidence of potential renal failure creatine levels will be measured and participants with a creatinine clearance < 30 mL/min will be excluded.
8. Known sulphite hypersensitivity
9. Pregnant or breastfeeding women

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All participants will received the intervention,
Participants with a confirmed genetic diagnosis of PWS, will be assigned to the PWS group. Healthy volunteers will be assigned to the Typically Developing control group.
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis
The effect of acamprosate on the 1H-MRS inhibitory index and functional connectivity will be measured with repeated-measures analysis of variance with drug as the within-subject (placebo and acamprosate) and group (PWS and controls) as the between subject. Pearson product-moment or Spearman correlations will be performed to explore the relationship between brain responsivity to acamprosate and emotional and behavioural problems.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 304380 0
Charities/Societies/Foundations
Name [1] 304380 0
Foundation for Prader-Willi Research
Address [1] 304380 0
340 S. Lemon Ave, #3620
Walnut, CA 91789
Country [1] 304380 0
United States of America
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
Camperdown, NSW, 2006
Country
Australia
Secondary sponsor category [1] 304632 0
Other Collaborative groups
Name [1] 304632 0
Sunshine Coast Mind and Neuroscience Thompson Institute
Address [1] 304632 0
Level 1, Thompson Institute, 12 Innovation Parkway,
Birtinya, QLD 4575
Country [1] 304632 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 304817 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 304817 0
Level 3, Administration Building (F23)
University of Sydney
Camperdown, NSW 2006
Ethics committee country [1] 304817 0
Australia
Date submitted for ethics approval [1] 304817 0
31/01/2020
Approval date [1] 304817 0
Ethics approval number [1] 304817 0

Summary
Brief summary
People with PWS and severe behaviour disturbance had significantly lower brain gamma-aminobutyric acid (GABA) levels than typically developing controls. GABA is the major inhibiting neurotransmitter in the brain, meaning it helps turn brain activity off. Unfortunately, there are currently no effective treatments for the core behaviours associated with PWS. We aim to address this issue by examining whether people with PWS show an increase in brain GABA levels in response to the medication acamprosate (a GABA modulator). If we find that they do, then this then this will help identify a new potential target for treatment in PWS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98302 0
Dr Lauren Rice
Address 98302 0
Brain and Mind Centre,
94 Mallet Street, Camperdown, NSW 2006
Country 98302 0
Australia
Phone 98302 0
+61 2 9114 4106
Fax 98302 0
Email 98302 0
lauren.rice@sydney.edu.au
Contact person for public queries
Name 98303 0
Dr Lauren Rice
Address 98303 0
Brain and Mind Centre,
94 Mallet Street, Camperdown, NSW 2006
Country 98303 0
Australia
Phone 98303 0
+61 2 9114 4106
Fax 98303 0
Email 98303 0
lauren.rice@sydney.edu.au
Contact person for scientific queries
Name 98304 0
Dr Lauren Rice
Address 98304 0
Brain and Mind Centre,
94 Mallet Street, Camperdown, NSW 2006
Country 98304 0
Australia
Phone 98304 0
+61 2 9114 4106
Fax 98304 0
Email 98304 0
lauren.rice@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant confidentiality is strictly held in trust by the investigators, research staff, and the sponsoring institution and their agents. The study protocol, documentation, data and all other information generated will be held in strict confidence. No information concerning the study, or the data will be released to any unauthorised third party, without prior written approval of the sponsoring institution.
What supporting documents are/will be available?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5886 0
Ethical approval
Citation [1] 5886 0
Link [1] 5886 0
Email [1] 5886 0
lauren.rice@sydney.edu.au
Other [1] 5886 0
Ethics approval may be obtained by contacting the Chief investigator Dr Lauren Rice
Attachment [1] 5886 0
Summary results
No Results