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Trial registered on ANZCTR


Registration number
ACTRN12625000147482
Ethics application status
Approved
Date submitted
16/01/2025
Date registered
7/02/2025
Date last updated
7/02/2025
Date data sharing statement initially provided
7/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Gastro-intestinal transit and safety of tirzepatide in people with Prader-Willi Syndrome
Scientific title
Gastro-intestinal transit and safety of tirzepatide in people with Prader-Willi Syndrome
Secondary ID [1] 313719 0
PWSRF01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prader-Willi Syndrome 336321 0
Condition category
Condition code
Human Genetics and Inherited Disorders 332862 332862 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a 12-week pilot study in 10 people with PWS and obesity with or without type 2 diabetes (aim is to enrol 50% with T2D). There will be no placebo group as this is a preliminary trial. All participants will receive tirzepatide dose of 2.5 mg once weekly for 4 weeks. The dose will be increased to 5 mg once weekly for a further 4 weeks and then to a final dose of 10 mg once weekly for 4 weeks. The study drug will be self administered via subcutaneous injection using pre-loaded vials. Study drug returns will be collected at each clinic visit to monitor adherence.

A single-isotope gastric emptying study will be performed at baseline, 4 weeks and 12 weeks to assess gastric emptying and caecal arrival time (CAT). Participants will ingest a test meal with total caloric value 255 kcal and nutritional composition 72% carbohydrate, 24% protein, 2% fat and 2% fibre. The meal comprises 2 slices of bread, 30g strawberry jam and 2 egg whites (120g) radiolabelled with 0.5-1 mCi 99mTc-sulphur colloid and 120 ml water. Images will be acquired immediately after ingestion and at hourly intervals up to 6 hours to assess gastric emptying and caecal arrival time. Participants will need to fast for 10 hours before and up to 6 hours following the 99mTc-sulphur colloid labelled meal.

At baseline and week 12, directly after ingestion of the 99mTc-sulphur colloid labelled meal, participants will ingest a gas sensing capsule (Atmo Biosciences), a single-use, non-digestible capsule (28x11 mm). This capsule measures concentrations of hydrogen and carbon dioxide, temperature, capsule orientation and changes in the physical electromagnetic properties of the environment surrounding the capsule. Measurements are transmitted from the capsule at a frequency of 434 MHz to a patient-worn data receiver and subsequently uploaded to secure cloud storage via mobile device for analysis and review. The receiver, which allows for bowel movements to be recorded, is worn by participants until the capsule is excreted. The totality of this system provides a measurement of regional and whole gut transit time. It has been validated against the FDA-approved wireless motility capsule but not against scintigraphy. Unlike water-labelled 67Ga-EDTA studies, the current gold standard for measurement of colonic transit, the gas sensing capsule does not involve any radiation exposure nor do patients need to represent for images at 24, 48 and 72 hours.

To further assess lower bowel function, participants will be asked to complete a stool chart for 1 week before starting tirzepatide, at weeks 4, 8 and 12 of the study. They will also be asked to complete a validated questionnaire, with assistance from their carer, in plain language covering the Rome IV constipation criteria at week -1, weeks 5, 9 and 13.

At each study visit (baseline, week 4, week 8 and week 12), participants will be asked about gastro-intestinal symptoms. To test the efficacy of tirzepatide on weight loss and effects on appetite and behaviour, anthropometry, hyperphagia score, behaviour questionnaires will be taken at baseline and study completion (ie week 12). Arterial stiffness will be assessed at baseline, each dose escalation visit and the final study visit to assess if tirzepatide changes these parameters. Appetite and fullness will be assessed during the scintigraphic studies using validated visual analogue scales (VAS). To assess effects of tirzepatide on metabolic parameters a fasting blood test (to measure glucose, lipids, HbA1c and liver function) will be done at baseline and week 12. To assess whether tirzepatide improves sleep apnoea, overnight pulse oximetry will be assessed at baseline (before starting tirzepatide) and in the week before the final visit at the patient’s abode. Sleep apnoea is characterised by temporary disruptions in breathing, leading to decreased blood oxygen levels. Oximeters, worn on the finger or wrist, continuously monitor oxygen saturation levels throughout the night, and can thereby demonstrate whether there are any changes in the degree of sleep apnoea.
Intervention code [1] 330315 0
Treatment: Drugs
Comparator / control treatment
There will be no placebo group as this is a preliminary trial. All participants receive active treatment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340382 0
To assess gastric emptying in people with PWS
Timepoint [1] 340382 0
Baseline, 4 weeks and 12 weeks post-intervention commencement
Primary outcome [2] 340475 0
To assess caecal arrival time (ie a measure of small intestinal transit) in people with PWS
Timepoint [2] 340475 0
Baseline, 4 weeks and 12 weeks post-intervention commencement
Primary outcome [3] 340476 0
To assess colonic transit time in people with PWS
Timepoint [3] 340476 0
Baseline, 4 weeks and 12 weeks post-intervention commencement
Secondary outcome [1] 443913 0
To determine if tirzepatide results in weight loss in people with PWS
Timepoint [1] 443913 0
Baseline, 4 weeks, 8 weeks and 12 weeks post-intervention commencement
Secondary outcome [2] 444212 0
To determine if tirzepatide results in behavioural changes in people with PWS
Timepoint [2] 444212 0
Baseline and 12 weeks post-intervention commencement
Secondary outcome [3] 444213 0
To determine if tirzepatide results in metabolic improvements in people with PWS
Timepoint [3] 444213 0
Baseline and 12 weeks post-intervention commencement
Secondary outcome [4] 444214 0
To determine if tirzepatide results in sleep disordered breathing changes in people with PWS
Timepoint [4] 444214 0
Baseline and 12 weeks post-intervention commencement
Secondary outcome [5] 444215 0
To validate the Atmo capsule in measuring gastric emptying against scintigraphy
Timepoint [5] 444215 0
Baseline and 12 weeks post-intervention commencement
Secondary outcome [6] 444431 0
To validate the Atmo capsule in measuring caecal arrival time against scintigraphy
Timepoint [6] 444431 0
Baseline and 12 weeks post-intervention commencement
Secondary outcome [7] 444657 0
To determine if tirzepatide results in changes in arterial stiffness in people with PWS
Timepoint [7] 444657 0
Baseline, 4 weeks, 8 weeks and 12 weeks post-intervention commencement

Eligibility
Key inclusion criteria
1. People with PWS:
2. Male or female
3. Aged greater than or equal to 18 years of age
4. Concomitant disease status: with obesity (BMI greater than or equal to 27 kg/m2), with or without type 2 diabetes
5. Laboratory parameters: E.g. Adequate renal function as defined by creatinine less than or equal to 100 µmol/L, eGFR greater than or equal to 50 ml/min
6. Provision of consent by participant or medical guardian as appropriate and willingness to participate and comply with the study requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants who may have received an investigational new drug within the last 6 months.
2. People with type 2 diabetes taking a GLP1-analogue, insulin or a sulphonylurea
3. Circumstances/conditions which may interfere with the participant’s, parent’s or carer’s ability to give informed consent.
4. Participants with a history of pancreatitis or gastric dilatation as these conditions are likely to interfere with the evaluation of the participant’s safety and the study outcome.
5. Participants with an allergy to eggs as they cannot have the radio-labelled test meal used to assess gastric emptying, a key primary outcome of this study.
6. Participation in any research studies involving exposure to ionising radiation in the previous 12 months
6. As the following medication(s) can have interactive effects and may interfere with the participant’s ability to meet the study requirements, they cannot be administered during the clinical study: semaglutide, dulaglutide
7. It is extremely rare for a woman with PWS to conceive and most have secondary hypogonadism. In the rare event that a potential female participant has childbearing potential, if she is not willing to avoid becoming pregnant during the study, she will be excluded from study entry.

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
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/03/2025
Actual
Date of last participant enrolment
Anticipated
7/07/2025
Actual
Date of last data collection
Anticipated
29/09/2025
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27493 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 43602 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 318184 0
Charities/Societies/Foundations
Name [1] 318184 0
Prader-Willi Research Foundation of Australia
Country [1] 318184 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Country
Australia
Secondary sponsor category [1] 320570 0
None
Name [1] 320570 0
Address [1] 320570 0
Country [1] 320570 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316836 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 316836 0
Ethics committee country [1] 316836 0
Australia
Date submitted for ethics approval [1] 316836 0
07/10/2024
Approval date [1] 316836 0
24/12/2024
Ethics approval number [1] 316836 0
X24-0356 & 2024/ETH02305

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

Contacts
Principal investigator
Name 139154 0
A/Prof Tania Markovic
Address 139154 0
Charles Perkins Centre, Building D17, Royal Prince Alfred Hospital Clinic, 50 Missenden Road, Camperdown NSW 2050
Country 139154 0
Australia
Phone 139154 0
+61 0447 316 078
Fax 139154 0
Email 139154 0
tania.markovic@sydney.edu.au
Contact person for public queries
Name 139155 0
A/Prof Nick Fuller
Address 139155 0
Charles Perkins Centre, Building D17, Royal Prince Alfred Hospital Clinic, 50 Missenden Road, Camperdown NSW 2050
Country 139155 0
Australia
Phone 139155 0
+61 2 8627 1932
Fax 139155 0
Email 139155 0
nick.fuller@sydney.edua.u
Contact person for scientific queries
Name 139156 0
Tania Markovic
Address 139156 0
Charles Perkins Centre, Building D17, Royal Prince Alfred Hospital Clinic, 50 Missenden Road, Camperdown NSW 2050
Country 139156 0
Australia
Phone 139156 0
+61 0447 316 078
Fax 139156 0
Email 139156 0
tania.markovic@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


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
No additional documents have been identified.