Psilocybin in alcohol use disorder with comorbid depression - Randomized double-blind controlled pilot study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nimes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

5 Feb 2024 → 5 Mar 2025

Decision date (initial)

2023-12-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU DE NIMES / IRESP

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the feasibility of a trial comparing psilocybin with very low-dose psilocybin (control) in alcohol use disorder with depressive symptoms.

Secondary objectives 13

1. To assess the feasibility of a trial comparing psilocybin with very low-dose psilocybin (control) in alcohol use disorder with depressive symptoms by other paraclinical varia
2. To assess patient acceptability of psilocybin treatment for alcohol use disorder with depressive symptoms in both study groups.
3. To assess the impact on drinking outcomes of psilocybin treatment in alcohol use disorder with depressive symptoms compared in the two study groups.
4. To assess the impact of psilocybin treatment on craving (the irrepressible urge to consume a substance, in this case alcohol) in alcohol use disorder with depressive symptoms, compared with the two study groups.
5. To evaluate the impact on alcohol-related quality of life of psilocybin treatment in alcohol use disorder with depressive symptoms compared in the two study groups.
6. To assess the impact on dimensions of psychological functioning of psilocybin treatment in alcohol use disorder with depressive symptoms compared in the two study groups.
7. To assess the impact on cognitive functioning (social cognition) of psilocybin treatment in alcohol use disorder with depressive symptoms compared in the two study groups.
8. Evaluate the role of psychological factors at baseline D0 (response factors) on the evolution of the percentage of HDD in the last 4 weeks preceding week 12 (S12).
9. Evaluate the role of other treatments (response factors) on the evolution of the percentage of HDD (Heavy Drinking Day)in the last 4 weeks preceding week 12 (S12).
10. To evaluate the role of the quality of the hallucinogenic experience on the evolution of the percentage of HDD (Heavy Drinking Day)in the last 6 weeks preceding week 12 (S12).
11. Evaluate immune and inflammatory profiles and their evolution in the 2 groups before the first psilocybin administration and 3 weeks after, through the microbiota.
12. Evaluate immune and inflammatory profiles and the evolution of these profiles in the 2 groups before the first psilocybin administration and 3 weeks after, using plasma markers. markers.
13. Evaluate immune and inflammatory profiles and their evolution in the 2 groups before the first psilocybin administration and 3 weeks after, using structural and functional brain MRI.

Conditions and MedDRA coding

alcohol use disorder

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. A patient with a confirmed DSM-5 diagnosis of severe alcohol use disorder.
2. BDI II score (Beck Depression Inventory) ≥ 14.
3. The last drink must have been consumed between 60 and 14 days before the inclusion visit.
4. The patient must have had at least 1 HDD during the last drinking period
5. The patient must have given his/her informed and signed consent
6. The patient must be insured or beneficiary of a health insurance plan
7. The patient is at least 18 years old

Exclusion criteria 15

1. Schizophrenic disorder, or any history of psychotic disorder as judged by the clinician.
2. past or current manic or hypomanic episode
3. Need for antipsychotic treatment that may interfere with psilocybin.
4. Suicidal ideation in progress, scripted (as judged by the clinician).
5. First-degree relative with a diagnosis of psychotic disorder or type 1 bipolar disorder.
6. High risk of negative emotional or behavioral response based on investigator's clinical judgment
7. Patients with dementia or severe cognitive impairment
8. Score CIWA-R ≥ 8.
9. Medical conditions that would prevent safe participation in the trial
10. History of hallucinogen use disorders, any use in the past year or > 25 lifetime uses.
11. Dependence on cocaine, psychostimulants, opioids or cannabis (last 12 months)
12. Current non-medical use of cocaine, psychostimulants or opioids (past 30 days).
13. Severe ECG anomalies
14. No access to email.
15. Insufficient understanding of French to complete questionnaires.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Collection of the number of patients who completed the two Psilocybin intake sessions out of the two planned as an approximation of feasibility.

Secondary endpoints 13

1. Number of patients screened per month/number of patients included per month. Average time (days) between screening and inclusion. Rate (%) of eligible patients included in the study. Rate (%) of included patients who had at least one treatment session. Rate (%) of assessment sessions performed. Duration of assessment sessions (min).
2. Number of patients leaving the study prematurely for any reason. Collection of reasons for patient drop-out.
3. Decrease in percentage of heavy drinking days in last 4 weeks prior to week 6 (or discharge if later; S6) and at week 12 (S12) vs. baseline (last 4 weeks drinking period). Total alcohol consumption in the last 4 weeks prior to week 6 (or discharge if later) and at week 12 compared with baseline (consumption period in last 4 weeks). Time to first drink (days). Time to first day of heavy drinking (days).
4. Craving Experience Questionnaire (CEQ) scores at D0 and W12.
5. Alcohol quality of life scale (AQoLS; 56) scores at D0 and W12.
6. Scores on the Beck Depression Inventory (BDI II), Beck Anxiety Inventory (BAI), Difficulties in Emotion Regulation Scale (DERS), Adult Rejection Sensitivity Questionnaire (A-RSQ) and Meaning in Life Questionnaire (MLQ) at D0, W3, W6 and W12.
7. Conflict indices and focus on the Visual Perspective Task (VPT) at D0 and Int2.
8. Factors assessed at D0: Adverse Childhood Events (ACE), Montreal Cognitive Assessment (MoCA), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), Relationship Scale Questionnaire (RSQ) attachment score.)
9. Collection of other drug treatments by class.
10. 5D-ASC (5-Dimensional Altered States of Consciousness Questionnaire) scores at the end of Psilo1 and Psilo2. EEG parameters recorded before the first psilocybin administration (resting state), during the 1st administration (at the expected peak of the psychedelic effect) and during the integration session the day after the second psilocybin administration (resting state). Qualitative analysis of the verbatim of the integration session.
11. Blood sampling and determination of circulating 16sDNA, permeability and inflammation markers, microbiota analysis
12. Blood sampling and plasma marker analysis: cytokine immunoassay (TNFα, IL-1β, IL-6, IL-8, IL-10, MCP-1), epitranscriptomic mass spectrometry, blood proteome, biomarker discovery
13. Study brain anatomical anomalies and volume differences in certain brain regions.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nimes

Sponsor organisation

Centre Hospitalier Universitaire De Nimes

Address

Place Du Professeur Robert Debre

City

Nimes

Postcode

30900

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

Leonie Gazel

Public contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

Leonie Gazel

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

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

Application history

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