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Trial registered on ANZCTR


Registration number
ACTRN12624001474549p
Ethics application status
Submitted, not yet approved
Date submitted
26/03/2024
Date registered
18/12/2024
Date last updated
18/12/2024
Date data sharing statement initially provided
18/12/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
PAPAYA: Pharmacologically-Assisted Psychotherapy for social Anxiety in Young people with Autism
Scientific title
Pharmacologically-Assisted Psychotherapy for social Anxiety in Young people with Autism
Secondary ID [1] 311613 0
Sponsor reference number F22-443
Secondary ID [2] 311920 0
Protocol number ORY-P08-21-25 PAPAYA
Universal Trial Number (UTN)
U1111-1304-8866
Trial acronym
PAPAYA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Social Anxiety Disorder 333038 0
Autism Spectrum Disorder 336087 0
Condition category
Condition code
Mental Health 329744 329744 0 0
Anxiety
Mental Health 330036 330036 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
MDMA-ASSISTED PSYCHOTHERAPY:

Individual psychotherapy is manualized and adapted from Cognitive Behavioral Therapy for social anxiety in autism.

Participants undergo three 90-minute preparatory psychotherapy sessions, approximately a week apart. Following the prep sessions, each participant will attend two 8-hour MDMA-assisted psychotherapy sessions separated by 4 weeks. There will be four 60-90 minute integration psychotherapy sessions in the 4 weeks after each MDMA session, equalling a total of 8 integration sessions. Therapy is delivered by allied health practitioners (e.g. psychologists) trained in this method. MDMA-assisted sessions and most other psychotherapy sessions are delivered face-to-face. Some preparatory and/or integration sessions may be delivered via telehealth.

Preparatory sessions will focus on developing a collaborative relationship between participant and therapist, setting therapy expectations and developing a safety plan. Medication-assisted psychotherapy sessions will include periods of quiet introspection and will employ the cognitive behavioural framework to discuss material arising during these periods, as well as reflecting on cognitions identified as related to social anxiety, and some exposure activities. Integration sessions will include reflecting on experiences and learnings in the medication-assisted sessions and generalising these learnings into everyday life using cognitive behavioural techniques.

MDMA DOSE:
Session 1, Initial Dose 1.0 mg/kg (Administered at the beginning of the session once baseline checks (e.g., medical review; biochemical tests for pregnancy and recent drug and alcohol use; adverse events) are completed; oral)
Session 1, Supplemental Dose 0.5mg/kg (Administered 2.5-3 hours post initial dose if indicated; oral)
Session 2, Initial Dose 1.5 mg/kg if Session 1 dose well tolerated, or 1.0 mg/kg (Administered at the beginning of the session once baseline checks (e.g., medical review; biochemical tests for pregnancy and recent drug and alcohol use; adverse events) are completed; oral)
Session 2, Supplemental Dose 0.5mg/kg (Administered 2.5-3 hours post initial dose if indicated; oral)

MDMA doses are rounded to the nearest 40 mg with a maximum initial dose of 120 mg.

STUDY SETTING
The study will be conducted at Orygen Clinical Trials Unit in Melbourne and the Brain and Mind Centre at the University of Sydney.

FIDELITY
All participants will be asked for permission to video record sessions for ongoing clinician training and fidelity assessment.

ALLIED HEALTH PRACTITIONERS
All therapists will be clinically experienced allied health providers. Study specific clinician training will be delivered by study PIs who are experts in the field (clinical psychologists and psychiatrists). Training (between five and ten, 2-hour training sessions) will include didactic training, guided reading, discussion, and role plays and be delivered before the first trial participant is randomised.
Intervention code [1] 328084 0
Treatment: Drugs
Intervention code [2] 328280 0
Behaviour
Comparator / control treatment
Placebo-assisted psychotherapy: Participants will undergo the same treatment as the MDMA-assisted psychotherapy group, receiving placebo capsules during the two 8-hour psychotherapy sessions.

Active control 1: dexamfetamine-assisted psychotherapy (reference comparator). Participants will undergo the same treatment as the MDMA-assisted psychotherapy group, receiving dexamfetamine capsules during the two 8-hour psychotherapy sessions.

DEXAMFETAMINE DOSE:
Session 1, Initial Dose 20 mg (oral)
Session 1, Supplemental Dose 10 mg (Administered 2.5-3 hours post initial dose if indicated; oral)
Session 2, Initial Dose 20 mg (oral)
Session 2, Supplemental Dose 10 mg (Administered 2.5-3 hours post initial dose if indicated; oral)


Active control 2: Diphenhydramine-assisted psychotherapy. Participants will undergo the same treatment as the MDMA-assisted psychotherapy group, receiving diphenhydramine capsules during the two 8-hour psychotherapy sessions.

DIPHENHYDRAMINE DOSE
Session 1, Initial Dose 50 mg (oral)
Session 1, Supplemental Dose 0 mg (Administered 2.5-3 hours post initial dose if indicated; oral)
Session 2, Initial Dose 75 mg (oral)
Session 2, Supplemental Dose 0 mg (Administered 2.5-3 hours post initial dose if indicated; oral)

Active control 3: Lorazepam-assisted psychotherapy. Participants will undergo the same treatment as the MDMA-assisted psychotherapy group, receiving lorazepam capsules during the two 8-hour psychotherapy sessions.

LORAZEPAM DOSE
Session 1, Initial Dose 2 mg (oral)
Session 1, Supplemental Dose 0 mg (Administered 2.5-3 hours post initial dose if indicated; oral)
Session 2, Initial Dose 3 mg (oral)
Session 2, Supplemental Dose 0 mg (Administered 2.5-3 hours post initial dose if indicated; oral)
Control group
Active

Outcomes
Primary outcome [1] 337536 0
Social Anxiety
Timepoint [1] 337536 0
Week 12 (change from baseline)
Secondary outcome [1] 432243 0
Safety and tolerability (assessed as a composite secondary outcome)
Timepoint [1] 432243 0
(a) baseline, week 6, week 10, week 12, 6month and 12 month follow up research follow up assessments
(b) Baseline, medication assisted therapy 1 and 2, week 6, week 10, week 12, 6month and 12 month follow up
(c) Baseline, prep session 1-3, medication assisted therapy 1 and 2, 8 integration sessions and at week 6, week 10, week 12, 6month and 12 month research follow up assessments
(d) Neurocognitive Assessment at baseline and week 12 research follow up assessment
(e) baseline, 6month and 12 month follow up research follow up assessments
Secondary outcome [2] 432244 0
Social anxiety remission
Timepoint [2] 432244 0
week 12 (change from baseline)
Secondary outcome [3] 432245 0
depression
Timepoint [3] 432245 0
weeks 6, 10, 12, 6 and 12-month (change from baseline)
Secondary outcome [4] 432246 0
social skills
Timepoint [4] 432246 0
weeks 6, 10, 12, 6 and 12-month follow-up (change from baseline)
Secondary outcome [5] 432247 0
Quality of life
Timepoint [5] 432247 0
weeks 6, 10, 12, 6 and 12-month follow-up (change from baseline)
Secondary outcome [6] 432248 0
ADHD symptoms
Timepoint [6] 432248 0
week 12, 6 and 12-month follow-up (change from baseline)
Secondary outcome [7] 432249 0
psychological distress
Timepoint [7] 432249 0
week 6, 10, 12, 6 and 12-month follow-up (change from baseline)
Secondary outcome [8] 432250 0
Social anxiety
Timepoint [8] 432250 0
6, 10 weeks, 6 and 12-month follow-up (change from baseline)
Secondary outcome [9] 442627 0
Disability
Timepoint [9] 442627 0
weeks 6, 10, 12 and months 6 and 12 (change from baseline)

Eligibility
Key inclusion criteria
1. 16-25 years old at consent;
2. ASD diagnosed in the past year or as assessed with the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) Module 4;
3. Current diagnosis of DSM-5 Social Anxiety Disorder (using the SCID 5);
4. Ability to provide informed consent (sufficient English and IQ>70 assessed with the Weschler Test of Adult Reading).

Minimum age
16 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable to safely abstain from alcohol for 48 hours before medication-assisted therapy sessions;
2. Unable to abstain from cannabis for 48 hours before medication-assisted therapy sessions;
3. Use of any illicit drug other than cannabis on average > 2 days per week over the past 4 weeks at screening;
4. Unstable medical conditions or contraindications for study medications, assessed with medical exam, electrocardiogram, and clinical blood tests, and as determined by the trial doctor;
5. Current treatment with contraindicated medications that cannot be safely discontinued as determined by the trial doctor;
6. Current or past DSM-5 psychotic or bipolar illness, as assessed by the SCID-5;
7. Acute suicidality or severe disturbance likely to interfere with the ability to comply with the study protocol;
8. Significant speech, visual, or auditory impairment likely to interfere with treatment; and
9. Pregnancy, breast feeding or, if sexually active, no effective contraception (participants capable of becoming pregnant only).

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)
Randomisation will employ a computer-generated random sequence. Codes will be securely held separately from researchers within the Orygen proprietary, in-house web-based Research Project Management System (RPMS), which automates randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned; randomisation will be stratified by site
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/01/2025
Actual
Date of last participant enrolment
Anticipated
15/01/2027
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
156
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC

Funding & Sponsors
Funding source category [1] 315921 0
Government body
Name [1] 315921 0
Department of Health and Aged Care Medical Research Future Fund. 2021 Innovative Therapies For Mental Illness Grant Opportunity
Country [1] 315921 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Orygen
Address
Country
Australia
Secondary sponsor category [1] 318086 0
None
Name [1] 318086 0
Address [1] 318086 0
Country [1] 318086 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314766 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 314766 0
Ethics committee country [1] 314766 0
Australia
Date submitted for ethics approval [1] 314766 0
25/10/2022
Approval date [1] 314766 0
Ethics approval number [1] 314766 0

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

Contacts
Principal investigator
Name 132662 0
A/Prof Gill Bedi
Address 132662 0
Orygen, 35 Poplar Rd Parkville, Victoria 3052
Country 132662 0
Australia
Phone 132662 0
+613 9966 9435
Fax 132662 0
Email 132662 0
gill.bedi@orygen.org.au
Contact person for public queries
Name 132663 0
Gill Bedi
Address 132663 0
Orygen, 35 Poplar Rd, Parkville, Victoria 3052
Country 132663 0
Australia
Phone 132663 0
+613 9966 9435
Fax 132663 0
Email 132663 0
gill.bedi@orygen.org.au
Contact person for scientific queries
Name 132664 0
Gill Bedi
Address 132664 0
Orygen, 35 Poplar Rd Parkville, Victoria 3052
Country 132664 0
Australia
Phone 132664 0
+613 9966 9435
Fax 132664 0
Email 132664 0
gill.bedi@orygen.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual Participant Data of primary outcomes will be available.
When will data be available (start and end dates)?
They will be available after the main results have been published for an indefinite time.
Available to whom?
Data will potentially be available to researchers from not-for profit organisations, commercial organisations or other based in any location. All data requests will be considered by the data custodian and the primary sponsor on a case-by-case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted. For further information, see Orygen data management policy.
Available for what types of analyses?
To any type of analyses. Assessed on a case-by-case basis
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health). Search for the ACTRN number in the catalogue to find datasets associated with this trial.


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.