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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000530325
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
10/09/2025
Date registered
Help: Date registered
29/04/2026
Date last updated
Help: Date last updated
29/04/2026
Date data sharing statement initially provided
Help: Data sharing statement date
29/04/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
Schizophrenia and Weight Improvement From Tirzepatide (SWIFT)
Scientific title
Schizophrenia Platform for Improving Recovery with Integrated Trials (SPIRIT) – Appendix C: Domain-Specific Appendix GLP-1RA - Schizophrenia and Weight Improvement From Tirzepatide (SWIFT)
Additional trial identifiers [1] 316258 0
None
Universal Trial Number (UTN)
Trial acronym
SWIFT
Related trial records

Health condition
Health condition(s) studied:
Schizophrenia 337198 0
Metabolic Disorders 337199 0
Obesity 337200 0
Condition category
Condition code
Mental Health 333606 333606 0 0
Schizophrenia
Diet and Nutrition 333607 333607 0 0
Obesity
Metabolic and Endocrine 333608 333608 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
The study will include 106 individuals with schizophrenia or schizoaffective disorder who will be randomised to receive weekly injections of either subcutaneous Tirzepatide (titrated 2.5mg for 4 weeks, 5mg for 4 weeks, 7.5mg for 4 weeks, 10mg for the duration of the study) or placebo for 24 weeks in addition to their normal routine care. The tirzepatide will be administered by registered mental health clinical trial nurses, who will also monitor adherence. As schizophrenia and schizoaffective disorder are heterogeneous conditions, routine care will vary from individual to individual.
Intervention code [1] 330874 0
Treatment: Drugs
Description of the comparator or control
This study will use a subcutaneous placebo injection (0.9% sodium chloride) adjunct to routine care as a comparator condition. As with the intervention, the placebo injection will be administered by a registered mental health clinical trial nurse, who will also monitor adherence.
Control group
Placebo

Outcomes
Primary outcome [1] 341185 0
Percentage of body weight change
Timepoint [1] 341185 0
Baseline and weekly until week 24, and then at week 52 optional follow-up post-first treatment dose
Secondary outcome [1] 449374 0
Psychosis symptoms
Timepoint [1] 449374 0
Screening and week 24 post-first treatment dose
Secondary outcome [2] 450317 0
Illness severity (clinician reported)
Timepoint [2] 450317 0
Baseline (CGI-S), weeks 12 and 24 post-first treatment dose
Secondary outcome [3] 450318 0
Illness severity (self-reported)
Timepoint [3] 450318 0
Baseline, weeks 12 and 24 post-first treatment dose
Secondary outcome [4] 450319 0
Quality of life
Timepoint [4] 450319 0
Baseline and week 24 post-first treatment dose
Secondary outcome [5] 450320 0
Depressive symptoms
Timepoint [5] 450320 0
Baseline and week 24 post-first treatment dose
Secondary outcome [6] 450321 0
Smoking
Timepoint [6] 450321 0
Baseline, weeks 12 and 24 post-first treatment dose
Secondary outcome [7] 450322 0
Weight change (as a binary outcome >5% bodyweight change)
Timepoint [7] 450322 0
Baseline and 24 weeks post-first treatment dose
Secondary outcome [8] 450808 0
Number of dropouts
Timepoint [8] 450808 0
24 weeks post-first treatment dose.
Secondary outcome [9] 456396 0
Illness severity (clinician rated)
Timepoint [9] 456396 0
Weeks 12 and 24 post-first treatment dose
Secondary outcome [10] 456397 0
Anxiety symptoms
Timepoint [10] 456397 0
Baseline and week 24 post-first treatment dose
Secondary outcome [11] 456398 0
Stress
Timepoint [11] 456398 0
Baseline and week 24 post-first treatment dose
Secondary outcome [12] 456399 0
Weight change (as a binary outcome >10% bodyweight change)
Timepoint [12] 456399 0
Baseline and 24 post-first treatment dose
Secondary outcome [13] 456400 0
Weight change (as a binary outcome >15% bodyweight change)
Timepoint [13] 456400 0
Baseline and 24 post-first treatment dose
Secondary outcome [14] 456401 0
Body Mass Index (BMI)
Timepoint [14] 456401 0
Height will only be measured at baseline. Weight will be measured at baseline and every week until 24 weeks post-first treatment dose
Secondary outcome [15] 456402 0
Waist circumference
Timepoint [15] 456402 0
Baseline, weeks 4, 8, 12, 16, 20, and 24 weeks post-first treatment dose
Secondary outcome [16] 456403 0
Hip-waist ratio
Timepoint [16] 456403 0
Baseline, weeks 4, 8, 12, 16, 20, and 24 weeks post-first treatment dose
Secondary outcome [17] 456404 0
Blood pressure (sitting)
Timepoint [17] 456404 0
Baseline and weeks 1,2,3,4,8,12,16,20, and 24 weeks post-first treatment dose
Secondary outcome [18] 456405 0
Blood pressure (standing)
Timepoint [18] 456405 0
Baseline and weeks 1,2,3,4,8,12,16,20, and 24 weeks post-first treatment dose
Secondary outcome [19] 456406 0
HbA1c
Timepoint [19] 456406 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [20] 456407 0
Fasting glucose
Timepoint [20] 456407 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [21] 456408 0
Fasting insulin
Timepoint [21] 456408 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [22] 456409 0
HOMA-IR (Homeostasis model assessment of insulin resistance)
Timepoint [22] 456409 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [23] 456410 0
Total cholesterol
Timepoint [23] 456410 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [24] 456411 0
Triglycerides
Timepoint [24] 456411 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [25] 456412 0
HDL (High-density lipoprotein)
Timepoint [25] 456412 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [26] 456413 0
LDL (Low-density lipoprotein)
Timepoint [26] 456413 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [27] 456414 0
White blood cell count
Timepoint [27] 456414 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [28] 456415 0
Neutrophils
Timepoint [28] 456415 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [29] 456416 0
Lymphocytes
Timepoint [29] 456416 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [30] 456417 0
Extended Liver Function Tests
Timepoint [30] 456417 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [31] 456418 0
Blood clozapine levels (only for participants prescribed clozapine)
Timepoint [31] 456418 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [32] 456419 0
Blood norclozapine levels (only for participants prescribed clozapine)
Timepoint [32] 456419 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [33] 456420 0
Amylase
Timepoint [33] 456420 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [34] 456421 0
Lipase
Timepoint [34] 456421 0
Screening, and weeks 12 and 24 post-first treatment dose
Secondary outcome [35] 456422 0
Stool consistency
Timepoint [35] 456422 0
Baseline, weeks 1, 2, 3, 8, 12, 16, 20 and 24 post-first treatment dose
Secondary outcome [36] 456423 0
Heart rate
Timepoint [36] 456423 0
Baseline and weeks 1,2,3,4,8,12,16,20, and 24 weeks post-first treatment dose

Eligibility
Key inclusion criteria

SWIFT inclusion criteria:
1. BMI equal or greater than 30 kg/m2 or BMI equal to or more than 27 kg/m2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease, at baseline.
2. Has been on any antipsychotic medication for a period of at least 12 weeks.
3. Not currently on tirzepatide or any other GLP-1RAs.
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
SPIRIT exclusion criteria:
1. Known allergies to any part of the formulation of the investigational product.
2. Any concomitant disease or condition that according to the investigator’s assessment makes the patients unsuitable for platform trial participation.
3. Inability to follow the study instructions and procedures.
4. People who are unable to understand or communicate in English.

SWIFT exclusion criteria:
1. Known allergies to tirzepatide or other GLP-1RAs or any part of the formulation of the investigational product.
2. GLP-1RAs in the previous 6 months.
3. Obesity induced by other endocrinologic disorder (e.g., Cushing Syndrome, untreated Hypothyroidism).
4. Current use of any weight-lowering therapy including: pramlintide, sibutramine, orlistat, zonisamide, topiramate or phenteremine (either by prescription or as part of a clinical trial or self managed).
5. Participants treated with corticosteroids or other hormone therapy (except oestrogens or thyroxine) for greater than 10 days.
6. Chronic kidney disease (eGFR<60mL/min).
7. History of medullary thyroid adenoma or carcinoma, and patients with or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
8. History of pancreatitis.
9. Previous surgical treatment of obesity.
10. BMI <27kg/m2 at baseline.
11. Any concomitant disease or condition that according to the investigator’s assessment makes the patients unsuitable for trial participation.
12. For female participants, those currently pregnant, or planning to become pregnant or lactating or no acceptance to the use of effective contraception during the study period.
13. Diagnosis of Type 1 or Type 2 Diabetes mellitus as determined by fasting glucose and HbA1C.

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 involves contacting the holder of the allocation schedule who is located "off-site"
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to one of the treatment groups, using a computer-generated randomisation table. Participants will receive either active treatment or placebo in a 1:1 ratio.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
This trial will employ a Bayesian statistical framework. This flexible form of analysis combines prior knowledge with data collected during the trial to produce probabilistic estimates of treatment efficacy, and is flexible when/if adding extra arms into the study.

Posterior distributions will be used to quantify uncertainty, and credible intervals will be used to describe the range of likely treatment effects.

Hypotheses
A superiority hypothesis will be evaluated comparing tirzepatide with placebo. The null hypothesis will be:

The posterior probability that the treatment effect is less than or equal to the Minimally Clinically Important Difference (MCID) at endpoint.

The alternative hypothesis will be:

The posterior probability that the treatment effect exceeds the MCID at endpoint.

If the 95% credibility interval of the treatment effect excludes the null, the treatment will be considered superior.

The primary analysis objective will be:
(i) to evaluate the difference in mean percentage weight loss at the primary endpoint (week 24) between patients allocated to receive tirzepatide and patients allocated to receive placebo,

with an additional objective:

(ii) to evaluate the difference in mean percentage weight loss at the primary endpoint (week 24) between patients with previous use of metformin who were allocated to receive tirzepatide and patients who were metformin-naïve at baseline and were allocated to receive tirzepatide.

Based on the intention-to-treat population, the primary outcome will be evaluated using a Bayesian hierarchical model, with fixed effects for treatment arm, time, study site and treatment arm by time interaction, anda random effect for each participant. The model will use non-informative priors for fixed effects and penalised complexity priors for random effects, and INLA will be used to implement the model.

For the primary outcome, the mean posterior summaries for the treatment effect with 95% credibility intervals will be used.

This approach will also be used to analyse all secondary and exploratory objectives.

Number-needed-to-treat will be calculated based on the proportions of participants in each intervention with >5, 10, and 15% weight loss. Sub-group analyses will be performed by antipsychotic type and metformin use at baseline where feasible.

Sensitivity analyses using a frequentist framework will also be conduced.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2026
Actual
Date of last participant enrolment
Anticipated
1/06/2028
Actual
Date of last data collection
Anticipated
30/06/2029
Actual
Sample size
Target
106
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment postcode(s) [1] 44687 0
4006 - Herston
Recruitment postcode(s) [2] 44688 0
4215 - Southport
Recruitment postcode(s) [3] 44689 0
3020 - Sunshine
Recruitment postcode(s) [4] 44690 0
4305 - Ipswich
Recruitment postcode(s) [5] 44691 0
2145 - Westmead
Recruitment postcode(s) [6] 44692 0
5000 - Adelaide
Recruitment postcode(s) [7] 44693 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 44694 0
2031 - Randwick
Recruitment postcode(s) [9] 44695 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 318786 0
Government body
Name [1] 318786 0
Australian Department of Health, Disability and Ageing, Medical Research Future Fund (MRFF)
Country [1] 318786 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 321232 0
None
Name [1] 321232 0
Address [1] 321232 0
Country [1] 321232 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317394 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 317394 0
Ethics committee country [1] 317394 0
Australia
Date submitted for ethics approval [1] 317394 0
15/11/2023
Approval date [1] 317394 0
29/07/2024
Ethics approval number [1] 317394 0

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

Contacts
Principal investigator
Name 140918 0
Prof Dan Siskind
Address 140918 0
Metro South Addiction and Mental Health Service, 2218 Logan Road, Woolloongabba, QLD 4102
Country 140918 0
Australia
Phone 140918 0
+61 7 3317 1040
Fax 140918 0
Email 140918 0
[email protected]
Contact person for public queries
Name 140919 0
Dan Siskind
Address 140919 0
Metro South Addiction and Mental Health Service, 2218 Logan Road, Woolloongabba, QLD 4102
Country 140919 0
Australia
Phone 140919 0
+61 7 3317 1040
Fax 140919 0
Email 140919 0
[email protected]
Contact person for scientific queries
Name 140920 0
Dan Siskind
Address 140920 0
Metro South Addiction and Mental Health Service, 2218 Logan Road, Woolloongabba, QLD 4102
Country 140920 0
Australia
Phone 140920 0
+61 7 3317 1040
Fax 140920 0
Email 140920 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Ethical approval    SWIFT_103997 Ethical clearance letter_Initial_29_Jul_2024.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.