Psilocybin for hospitalized patients with treatment-resistant depression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Ziekenhuis Gent

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Psychiatry and Psychology [F] - Psychological Phenomena [F02], Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01], Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

22 Apr 2024 → ongoing

Decision date (initial)

2023-09-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Filament Health (Psilo Scientific Ltd. (PSILO)) · Ghent University Hospital

External identifiers

EU CT number

2022-501857-35-00

ClinicalTrials.gov

NCT06378229

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the safety of performing psilocybin-assisted psychotherapy in TRD in a hospitalized setting.

Secondary objectives 9

1. To assess the feasibility of performing psilocybin-assisted psychotherapy in TRD in a hospitalized setting.
2. To assess the longer-term safety of performing psilocybin-assisted psychotherapy in TRD.
3. To assess the preliminary outcomes of performing psilocybin-assisted psychotherapy in TRD in a hospitalized setting.
4. To assess the longer-term preliminary outcomes of performing psilocybin-assisted psychotherapy in TRD.
5. To investigate the neurophysiological effects of the psychedelic experience and its association to depressive outcome using electroencephalography (EEG).
6. To investigate qualitatively the psychedelic experience and its association to depressive outcome using an experiential perspective.
7. To quantitatively assess the effect of psilocybin-assisted psychotherapy on the relationship between the subjects and their partners.
8. To qualitatively assess treatment expectancies and experiences in both subjects and their partners.
9. To perform a prospective, observational and naturalistic follow-up until 1 year after the last psilocybin session.

Conditions and MedDRA coding

treatment-resistant depression

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age 18 years or older.
2. Diagnosis of major depressive disorder (single and recurrent episodes) of moderate to severe degree (MADRS score ≥ 20) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), without psychotic features. Included ICD-11 diagnoses are ICD-11: 6A70.1, 6A70.3, 6A71.1, 6A71.3.
3. Subjects have failed to respond to 2 or more antidepressant treatments with different working mechanisms, prescribed at the minimum effective dose for an adequate duration. Psychopharmacological treatments include SSRIs, SNRIs, TCAs, MAOIs, bupropion, mirtazapine, agomelatine, vortioxetine, esketamine. Augmentation with an atypical antipsychotic as an add-on treatment counts as a second treatment. Neuromodulatory treatments include Electroconvulsive Therapy (ECT) and repetitive Transcranial Magnetic Stimulation (rTMS).
4. The subjects must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead ECG performed at screening. - In 12-lead ECG, QTcF should be ≤ 450 ms for males or ≤ 470 ms for females and PR-interval < 220 ms at screening.
5. A partner is willing to participate in the study (a cohabiting relationship of at least 1 year).
6. The subject is able to fluently speak Dutch.
7. Inclusion criteria for the subject’s partner: Age 18 years or older.

Exclusion criteria 15

1. Currently comorbid or previously diagnosed DSM-5 diagnosis of a a) major depressive episode with psychotic features. b) psychotic disorder (defined as meeting DSM-5 criteria for any psychotic disorder) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. c) bipolar disorder (defined as meeting DSM-5 criteria for bipolar type 1 or bipolar type 2) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
2. Pregnant or breast-feeding women.
3. Those unable to give informed consent.
4. Those enrolled in another trial.
5. Exclusion criteria for the subject’s partner: Those unable to give informed consent.
6. A family history (first-degree relative) of psychosis and/or bipolar disorder.
7. Current active suicidal ideations.
8. Depression secondary to other medical conditions.
9. Medical diagnosis incompatible with psilocybin treatment: a) Cardiovascular conditions: recent stroke (< 1 year from signing of ICF), recent myocardial infarction (< 1 year from signing of ICF), uncontrolled hypertension (blood pressure > 140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF. b) Uncontrolled insulin-dependent diabetes mellitus. c) Uncontrolled epilepsy.
10. Biochemical or electrocardiographic abnormalities determined as clinically significant by a medical doctor.
11. Current intake of Lithium, Disulfiram, MAOIs or inhibitors of UGT1A9 and 1A10.
12. The subject has received any prior treatment with vagal nerve stimulation, or a deep brain stimulation device.
13. Women of childbearing potential not using adequate contraception (methods that can achieve a failure rate of less than 1%: combined hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence).
14. Currently comorbid diagnosed DSM-5 diagnosis of a a) drug or alcohol dependence syndrome (defined as meeting DSM-5 criteria for any dependence syndrome) on the MINI 7.0 in the last 3 months. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. b) cluster B personality disorder. Subjects will be screened for the presence of those personality traits by using the NEO-FFI-3. c) PTSD (defined as meeting DSM-5 criteria for PTSD) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
15. Men in a relationship with a woman of childbearing potential not using adequate contraception (see exclusion criterium 13)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The safety of performing psilocybin-assisted psychotherapy in TRD in a hospitalized setting (reported Serious Adverse Events (SAEs) and changes in vital signs and suicidal ideation/behavior (measured using the Columbia Suicide Severity Rating Scale (C-SSRS)) for the duration of the hospitalization phase (until 3 weeks after the last psilocybin session)).

Secondary endpoints 9

1. The feasibility of performing psilocybin-assisted psychotherapy in TRD in a hospitalized setting at 3 weeks after the last psilocybin session (recruitment and retention rates, acceptability of the intervention and procedures for the subjects as assessed through semi-structured interviews).
2. Reported AEs and changes in suicidal ideation/behavior (measured using the C-SSRS) until 12 weeks after the last psilocybin session.
3. Remission of depressive symptoms (Quick Inventory of Depressive Symptomatology – Self Report (QIDS-SR) ≤5, Montgomery Asberg Depression Rating Scale (MADRS) ≤6) and improvement on the State-Trait Anxiety Inventory (STAI), World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and Maudsley 3-item Visual Analogue Scale (M3VAS) at 3 weeks after the last psilocybin session, compared to baseline. Improvement on the Subjective Emotional Health Visual Analogue Scale (SEHVAS), as assessed
4. Remission of depressive symptoms (QIDS-SR ≤5, MADRS ≤6) and improvement on the STAI, WHOQOL-BREF and M3VAS at 6 weeks and 12 weeks after the last psilocybin session, compared to baseline. Improvement on the SEHVAS, as assessed by the partner, at 12 weeks after the last psilocybin session, compared to baseline.
5. Changes in brain activity as measured by EEG the day of the first integration session after each psilocybin session and at 12 weeks after the last psilocybin session, compared to baseline.
6. Improvement on the Client Experiencing Scale (EXP) after each psilocybin session (during an integration session) as compared to before each psilocybin session (during a preparation session), independent of changes on the Working Alliance Inventory – Short Revised (WAI-12). Changes on the EXP are correlated to the Mystical Experience Questionnaire (MEQ) scores and depressive outcome.
7. Improvement on the revised Dyadic Adjustment Scale (RDAS), for both the subject and the partner, at 3 weeks and 12 weeks after the last psilocybin session, compared to baseline. Improvement on the ZARIT-12 Burden scale (for the partner) at 3 weeks and 12 weeks after the last psilocybin session, compared to baseline.
8. Interpretative Phenomenological Analysis (IPA) of semi-structured interviews with both subjects and their partners performed at the start of the trial, at 3 weeks after the last psilocybin session and (if they consent) at 1 year after the last psilocybin session.
9. Descriptive analysis of the long-term evolution (mental state, occurrence of AEs, new therapies), assessed through monthly telephone calls and 2 (video) consultations (at 6 months and 1 year) up to one year after the last psilocybin session (if the subject consents). Evolution on the MADRS, WHOQOL-BREF and RDAS questionnaires, compared to baseline, at 6 months and 1 year after the last psilocybin session. Assessment of posttraumatic growth through PTGI-X 1 year after the last psilocybin session.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Ziekenhuis Gent

Sponsor organisation

Universitair Ziekenhuis Gent

Address

Corneel Heymanslaan 10

City

Gent

Postcode

9000

Country

Belgium

Scientific contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Cisse Geleyn

Public contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Cisse Geleyn

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 41 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications