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Trial registered on ANZCTR


Registration number
ACTRN12624001160527
Ethics application status
Approved
Date submitted
6/08/2024
Date registered
24/09/2024
Date last updated
29/09/2024
Date data sharing statement initially provided
24/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Opening up
Scientific title
The efficacy of psilocybin assisted psychotherapy (PAP) for treatment resistant obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), and anorexia nervosa (AN); a pilot, single-arm basket trial
Secondary ID [1] 311423 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
obsessive-compulsive disorder 332710 0
body dysmorphic disorder 332711 0
anorexia nervosa 332712 0
Condition category
Condition code
Mental Health 329425 329425 0 0
Other mental health disorders
Mental Health 331459 331459 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention involves psilocybin assisted psychotherapy. All participants will receive two psilocybin doses of 25mg, 4 weeks apart, and adjunct therapy-preparation, support during dosing, and integration. The psilocybin will be aministered orally, via a capsule.

A therapist dyad will provide non-directive psychotherapy, atleast one therapist will be a consultant psychiarist or psychiatry registrar. The psychotherapy will involve three distinct phases: (1) Preparation: emphasising therapeutic alliance, non-avoidance training, psychological and practical preparation for dosing sessions, nature of and relationship to distress, anxiety management strategies, the importance of set and setting, and intention formation; (2) Dosing session: establishing suitable set and setting, non-directive support; (3) Integration: focus on sustaining the change, emotion and body-focused therapy, meaning-centred integration into wider context, mindfulness training, ongoing peer- and professional support, and facilitating contextual changes to support outcomes.

Preparatory sessions will take approximately 3 hours (across 1-2 sessions, based on participant preference), 1-week prior to the first dosing session. Two dosing sessions will take 8 hours each. Integration sessions will be conducted across 2 sessions following each dosing session; the first will be conducted within 2-days after each dosing session, and second within a week after the dosing session. Two integration will be provided following each dosing session- 4 in total. Any deviations from the intended therapeutic component of the trial will be monitored. Psychotherapy sessions will be conducted face-to-face. If it is not convenient for particpants to make all face-to-face sessions, they may participate in the second integration session online.
Intervention code [1] 327866 0
Treatment: Drugs
Intervention code [2] 327867 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337240 0
Obsessive-compulsive symptom severity (OCD participants)
Timepoint [1] 337240 0
Baseline and 8-week post-baseline.
Primary outcome [2] 337241 0
Body-dysmorphic symptom severity (BDD participants)
Timepoint [2] 337241 0
Baseline and 8-week post-baseline.
Primary outcome [3] 337242 0
Anorexia nervosa symptom severity (AN participants)
Timepoint [3] 337242 0
Baseline and 8-week post-baseline.
Secondary outcome [1] 431174 0
Depression
Timepoint [1] 431174 0
Baseline and 8-week post-baseline.
Secondary outcome [2] 431175 0
Anxiety
Timepoint [2] 431175 0
Baseline and 8-week post-baseline.
Secondary outcome [3] 431176 0
Anxiety
Timepoint [3] 431176 0
Baseline and 8-week post-baseline.
Secondary outcome [4] 431177 0
Negative affect
Timepoint [4] 431177 0
Baseline and 8-week post-baseline.
Secondary outcome [5] 431178 0
Insight into symptoms
Timepoint [5] 431178 0
Baseline and 8-week post-baseline.
Secondary outcome [6] 431179 0
Quality of life
Timepoint [6] 431179 0
Baseline and 8-week post-baseline.
Secondary outcome [7] 431180 0
Global functioning- patient reported
Timepoint [7] 431180 0
Baseline and 8-week post-baseline.
Secondary outcome [8] 431181 0
Global functioning- clinician assessment
Timepoint [8] 431181 0
Baseline and 8-week post-baseline.
Secondary outcome [9] 431183 0
Anxiety relating to appearance- BDD participants only
Timepoint [9] 431183 0
Baseline and 8-week post-baseline.
Secondary outcome [10] 431184 0
Obsessive beliefs- OCD participants only
Timepoint [10] 431184 0
Baseline and 8-week post-baseline.
Secondary outcome [11] 431185 0
Insight into eating disorder symptoms- AN participants only
Timepoint [11] 431185 0
Baseline and 8-week post-baseline.

Eligibility
Key inclusion criteria
i) Adults aged 18 to 65 years.
ii) Primary diagnosis of OCD, BDD or AN according to the DSM-5, determined by Structured Clinical Interview for DSM-5 Disorder (SCID-5), The Body Dysmorphic Disorder Diagnostic Module (BDD-DM) and Eating Disorder Examination (EDE).
iii) Moderate to severe symptom severity indicated as a score 18 or greater on the YBOCS, 20 or greater on the BDD-YBOCS, 3 or greater on the shape and/or weight subscales of the EDE.
iv) Treatment resistance; defined as 1-year of illness with continuing symptoms for at least 6-months despite adequate engagement in conventional interventions for the condition. Specifically, conventional therapies for each condition are defined as:
OCD: a course of selective serotonin reuptake inhibitors (SSRIs) and at least one course of cognitive behavioural therapy (CBT) which must include exposure and response prevention (ERP) (Pallanti and Quercioli, 2006).
BDD: two courses of psychotherapy and/or pharmacology treatment, including at least one course of cognitive behavioural therapy (CBT), adequatea course of SSRIs or serotonin-norepinephrine reuptake inhibitor (SNRI).
AN: a course of SSRIs or SNRIs, and at least one in-patient admission or day patient program.
v) Illness duration of at least 1- year
vi) Absence of delusionality as indicated by a total score <18, and a score of <4 on the delusionality sub-scale on the BABS
vii) Absence of mania symptoms (only minor) as indicated by a score <20 on the YMRS
viii) If currently taking serotonergic antidepressants or atypical antipsychotics that block 5HT2A receptors, which can interfere with the mechanism of action of psilocybin, agree to, and can be, appropriately tapered off such concomitant medication with clinical team support.
ix) Under the care of a psychiatrist, psychologist, physician, or GP.
x) Proficient in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent.
xi) Participants who agree to be abstinent from illicit or extra-medical drug and alcohol use for at least 2 days prior to each psilocybin dosing.
xii) Participants who agree to have their drug dosing sessions recorded to video for treatment fidelity and clinical supervision within the study team.
xiii) Utilising effective contraception if female and of childbearing age
xiv) Capacity to provide adequate inform consent; demonstrated by an estimated IQ >79 assessed by the Weschler Abbreviated Scale of Intelligence (WASI) to ensure that study instructions can be understood, and by a revised version of the Evaluation to sign an informed consent document for research to ensure appropriate understanding of trial requirements (DeRenzo et al., 1998).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Psychiatric exclusions
i) Lifetime history of serious suicide attempts requiring hospitalisation or current suicidal ideation with intent warranting immediate hospitalisation.
ii) Current or past history of psychosis; DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Mania, determined by medical history and MINI assessment.
iii) First degree relative with diagnosed Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Mania.
iv) Presence of significant neurodevelopmental disorder (e.g., ADHD, autism, unremitting Tourette’s syndrome) that would reasonably impact the therapeutic effect of psilocybin.
v) Currently meets DSM-5 criteria for Dissociative Disorder, Bulimia Nervosa, or significant personality disorder judged to be incompatible with establishment of rapport or safe exposure to psilocybin, determined by clinical interview.
vi) Any current personal or situational factors that, in the opinion of the research team, might interfere with participation (for example, lacking social support, lacking a stable living situation, current domestic violence, or other ongoing trauma).
vii) A history of childhood trauma or other factors leading to a complex case of OCD, BDD, or AN.

General medical exclusions
i) Any disorder with known CNS involvement or disease, including seizures
ii) Hepatic dysfunction as indicated by the following values:
iii) -- GGT > 3 x ULN (upper limit of norm)
iv) -- AST > 3 x ULN
v) -- ALT > 3 x ULN
vi) -- Tot Bili > 3.0 mg/dL
vii) Known conditions putting participant at risk for hypercalcaemia, Cushing's syndrome, hypoglycaemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid syndrome.
viii) Cardiovascular conditions: uncontrolled hypertension (Systolic >140 and diastolic >90), angina, a clinically significant ECG abnormality (e.g., atrial fibrillation), TIA in the last 6 months, stroke, or cerebrovascular disease, peripheral or pulmonary vascular disease (no active claudication). This could include patients presenting with abnormal QT interval prolongation at screening or with a history of this (QTc at screening above 440 ms for men and above 470 ms for women).
ix) Renal insufficiency (creatinine clearance < 40 mL/min using the Cockcroft and Gault equation).
x) Insulin-dependent diabetes; if taking oral hypoglycaemic agents only excluded if they also have a history of hypoglycaemia.
xi) Females who are pregnant or nursing or are trying to get pregnant, or become pregnant during the study.
xii) Current hypothyroidism not responsive to treatment or untreated hypothyroidism.
xiii) Patients who weigh less than 40 kg or have a BMI <16 kg/m2.
xiv) Medical instability as indicated by significant weight loss (>3 kg) during screening period, orthostatic heart rate or blood pressure.
xv) Long-acting opioid pain medications (e.g., oxycodone sustained release, morphine sustained release -- which are usually taken at 12-hour intervals) will be allowed if the last dose occurred at least 6 hours before psilocybin administration; such medication will not be taken again until at least 6 hours after psilocybin administration.
xvi) Macro-dose (i.e., dose large enough to have perceivable hallucinogenic/psychedelic effects) of any hallucinogen or psychedelic (including psilocybin, MDMA, LSD, mescaline, DMT, and other similar hallucinogenic compounds) compounds within the past 12 months or > 10 macro-doses across lifetime.
xvii) Micro-dose of any hallucinogen or psychedelic compound within the past 6 months
xviii) Taking a contraindicated medication (SSRIs, SNRIs, MAOIs), which they do not wish to taper off, or is deemed inappropriate for them to taper by their treating clinician.
xix) Current or past history within the last 5 years of meeting DSM-5 criteria for alcohol or drug dependence (excluding caffeine and nicotine) determined by the MINI, DAST-10 and AUDIT.
xx) Use of illicit or extra-medical drugs or alcohol within the 2 days prior to each dosing session
xxi) Currently using any of the following potent metabolic inducers or inhibitors: Inducers - Rifamycin (rifampin, rifabutin, rifapentine), anticonvulsants (carbamazepine, phenytoin, phenobarbital), nevirapine, efavirenz, paclitaxel, St John's Wort; Inhibitors - all HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin.
xxii) If medically required to receive any of the following drugs with low therapeutic index within 12 hours after receiving psilocybin: ergot alkaloids, pimozide, midazolam, triazolam, lovastatin, simvastatin, fentanyl.
xxiii) Any significant, uncorrected visual impairments, to ensure appropriate understanding of visual material.
xxiv) Participants will be excluded if they are non-binary or do not gender identify with their biological sex.
xxv) Unable to swallow tablets.
xxvi) Enrolled in another interventional trial

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 design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Baseline demographics, clinical characteristics, and recruitment/ enrolment/withdrawals will be analysed using descriptive statistics. H1 will be addressed by descriptive statistics, the % change in primary outcomes will be calculated for each participant, the number of responders (35% improvement in objective primary outcome) will be reported within each patient group. Comparably, H2 will be addressed by reporting the number of responders (50% improvement) for secondary outcomes of depression, anxiety, quality of life and disability.
For the explorative analysis, an intention-to-treat (ITT) analysis will be conducted using repeated measures linear mixed models. A model will be analysed for each patient group, with the dependent variable as the objective measure of symptom severity (YBOCS, BDD-YBOCS, EDS3), repeated measure will be Visit (each data point included), the random factor will be Subject.
For the explorative analysis regression analyses will be used and covariates/predictors will include secondary and explorative outcomes (BABS, OBQ, SAI-ED, TIPI, MEQ, 11D-ASC, EBI, PIQ, RAS-DS) that demonstrate significant correlations with the primary outcome to investigate possible predictors of symptom improvement across time points. Baseline predictors of response will also be investigated with the same approach, and baseline clinical characteristics (symptom severity, treatment resistance, comorbidities, insight, expectations of therapy, personality characteristics) as covariates. If predictors are identified for a dependent variable, a lagged model (predicts Y(t) from X(t-1)) will be analysed with the same repeated, random, and covariate variables to investigate directionality of predictors. The AR (1) covariance structure and change variables (t1-(t1-1)) will account for possible autocorrelation across repeated measures. The advantage of mixed linear modelling is that it is implemented for modelling case series data over time, allows for repeated or related measures, uneven datasets and missing data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2024
Actual
Date of last participant enrolment
Anticipated
31/12/2026
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 315694 0
University
Name [1] 315694 0
Swinburne University
Country [1] 315694 0
Australia
Primary sponsor type
University
Name
Swinburne University
Address
Country
Australia
Secondary sponsor category [1] 317801 0
None
Name [1] 317801 0
Address [1] 317801 0
Country [1] 317801 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314564 0
Swinburne University of Technology Human Research Ethics Committee
Ethics committee address [1] 314564 0
Ethics committee country [1] 314564 0
Australia
Date submitted for ethics approval [1] 314564 0
30/01/2024
Approval date [1] 314564 0
03/07/2024
Ethics approval number [1] 314564 0
20247696-19013

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

Contacts
Principal investigator
Name 132026 0
Prof Susan Rossell
Address 132026 0
Swinburne University, John Street, Hawthorn, 3122, VIC
Country 132026 0
Australia
Phone 132026 0
+61392148173
Fax 132026 0
Email 132026 0
srossell@swin.edu.au
Contact person for public queries
Name 132027 0
Susan Rossell
Address 132027 0
Swinburne University, John Street, Hawthorn, 3122, VIC
Country 132027 0
Australia
Phone 132027 0
+61392148173
Fax 132027 0
Email 132027 0
srossell@swin.edu.au
Contact person for scientific queries
Name 132028 0
Susan Rossell
Address 132028 0
Swinburne University, John Street, Hawthorn, 3122, VIC
Country 132028 0
Australia
Phone 132028 0
+61392148173
Fax 132028 0
Email 132028 0
srossell@swin.edu.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?
De-identified IPD will be made available upon reasonable request, in these instances an agreement will be put in place, and these details are yet to be determined. The type of data shared will depend on the request.
When will data be available (start and end dates)?
The data will be maintained for 15 years after study completion, and archived thereafter, there are no restrictions on the dates of data sharing. The study is expected to finish Dec 2026, and data sharing will be available thereafter.
Available to whom?
Requests may be made by anyone with a reasonable request, and will be reviewed on a case-by-case basis.
Available for what types of analyses?
There is no specified analysis for data sharing purposes.
How or where can data be obtained?
Data will be securely shared on a server in line with data transfer requirements and privacy policies.


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
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