Psilocybin-Assisted Therapy for Severe Alcohol Use Disorder

NCT06160232 | Recruiting Phase 2

• 2 other identifiers: CHUB-Psy-PATh for sAUD2022-002369-14
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Psilocybin-Assisted Therapy for Severe Alcohol Use Disorder: Protocol for a Double-Blind, Randomized, Placebo-Controlled, 7-month Parallel-Group Phase II Superiority Trial

Conditions

Severe Alcohol Use Disorder

Outcome Measures

Primary Outcomes (3)

• Primary clinical outcome: change in percentage of heavy drinking days

  The primary clinical outcome is the difference between the two treatment arms in terms of change from baseline (going back 8 weeks pre-enrolment) to 4 weeks post-hospital discharge (week 1 to 4 post-discharge) in the percentage of heavy drinking days. A heavy drinking day is defined as a day with ≥ 5 standard drinks/60g of alcohol for males, and ≥ 4 standard drinks/48g of alcohol for females. Alcohol consumption will be measured using the Timeline Follow-Back method (Sobell \& Sobell, 1992), a semi-structured interview that provides estimates of the daily quantity, frequency, and pattern of alcohol (and other drugs) use during a set time period. The method has demonstrated adequate to excellent reliability and validity over a wide range of studies and clinical contexts (Carey, 1997; Sobell et al., 1996).

  Baseline (going back to 8 weeks pre-enrolment) to 4 weeks post-hospital discharge

• Feasibility: recruitment and retention rate

  Recruitment and retention rate will be recorded and reported. A consort diagram displaying participant retention at each phase of the recruitment, screening and data collection process will be presented. We will report the numbers of individuals provided with participant information sheets who subsequently decided not to participate in the trial, number that underwent screening and number of drop-outs. For full transparency on inclusivity, information on the demographics and reason for exclusion will be reported from the screening dataset.

  Recruitment rate: at screening and enrolment. Retention rate: at each study visit

• Safety: adverse events

  Adverse events will be systematically assessed at each study visit and follow-ups. Adverse events summary tables will display the total number of participants reporting an adverse event and the percentage of participants (%) with an adverse event.

  At each study visit

Secondary Outcomes (16)

• Percent Heavy Drinking Days

  from pre-hospitalisation (up to 8 weeks pre-hospitalization) to 6 months post-hospital discharge (week 5 to 26 weeks)

• Drinks per Day

  from pre-hospitalisation (up to 8 weeks pre-hospitalization) to 4 weeks and 6 months post-hospital discharge

• Percent Days Abstinent

  from pre-hospitalisation (up to 8 weeks pre-hospitalization) to 4 weeks and 6 months post-hospital discharge

• EEG-derived auditory long-term potentiation

  Neuroplasticity EEG data will be collected pre-dosing and twice post-dosing (+1 day, +7 days)

• EEG-derived alcohol cue reactivity

  EEG data will be collected pre-dosing and twice post-dosing (+1 day, +7 days)

Study Arms (2)

high dose psilocybin

EXPERIMENTAL

31 participants will receive a single administration of 30mg psilocybin provided within the context of a brief standardized psychotherapeutic intervention.

Drug: Psilocybin (high dose)

low dose psilocybin (active placebo)

PLACEBO COMPARATOR

31 participants will receive a single administration of a very low dose of psilocybin (active placebo) provided within the context of a brief standardized psychotherapeutic intervention.

Drug: Active placebo (low dose of psilocybin)

Interventions

Psilocybin (high dose) DRUG

Psilocybin-assisted therapy

high dose psilocybin

Active placebo (low dose of psilocybin) DRUG

Placebo-assisted therapy

low dose psilocybin (active placebo)

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patients between 21 and 64 years old, with a BMI between 17.5 and 30 kg/m2 who
• Want to stop or decrease their drinking;
• Agree to have all psilocybin-assisted therapy sessions (preparation, administration, integration) and semi-structured interviews recorded;
• Have a diagnosis of Severe Alcohol Use Disorder (sAUD), according to the DSM-V (6 criteria or more), ascertained using the Mini International Neuropsychiatric Interview (M.I.N.I 7.0.2).
• Are not currently receiving any pharmacological treatment for sAUD and are willing to engage in all study requirements (including attending all study visits, preparatory sessions, integration sessions, follow-up sessions, and completing all study evaluations).
• Women of childbearing potential must have a negative serum pregnancy test at admission (day 1 +/-2) and a negative urine pregnancy test the day before psilocybin administration (day 19 +/-2).
• Good physical health with no unstable medical conditions, as determined by medical history, physical examination, routine blood labs, electrocardiogram, urine analysis, and urine toxicology.
• Willing to refrain from consuming psychoactive substances after enrolling in the study and during follow-up.
• Ability to provide voluntary written informed consent after receiving written information about the study protocol.
• Undergoing a 4-week alcohol detoxification program at the Brugmann University Hospital.
• Remaining abstinent from alcohol during the detoxification program (abstinence will be monitored using a breathalyzer during unannounced checks).
• Normal level of language comprehension (French).
• Affiliation to the Belgian social security system.

You may not qualify if:

• Allergy, hypersensitivity, or other adverse reactions to previous use of psilocybin or other hallucinogens.
• Uncorrected hypertension.
• Cardiovascular diseases, hepatic diseases, gastroenterological diseases, hematologic diseases, renal diseases, endocrine diseases, metabolic diseases, inflammatory diseases, neurological diseases or any other somatic condition that, in the opinion of the medical investigator (necessarily an M.D.), would pose a risk to the participant's participation in the study.
• Other somatic conditions that, in the opinion of the investigator, would pose a risk to the participant's participation in the study.
• Decompensated hepatic cirrhosis, defined by Child B or C score.
• Serious abnormalities of complete blood count or chemistries, biological abnormalities including TP \< 50%, albumin \< 35 g/L, total bilirubin \> 35 μmol/L, leading to a Child B or C score.
• Cognitive impairment (Folstein Mini Mental State Exam (Folstein et al., 1975) score \< 26).
• Alcohol withdrawal complication(s), seizure, head injury or stroke within the last 6 months.
• Current active acute stress disorder/post-traumatic stress disorder,
• Lifetime history of schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, unspecified), other psychotic disorders or bipolar spectrum disorders (Type I, II, unspecified).
• Lifetime history of major depressive episode with psychotic features.
• Significant risk of suicide according to clinician assessment.
• Family history of schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, unspecified), or other psychotic disorders, or bipolar Type I in first- or second-degree relatives.
• Severe cannabis use disorder according to the DSM-V.
• Need to take medication with significant potential to interact with classical psychedelics (e.g., antidepressants except selective serotonin reuptake inhibitors (SSRIs), antipsychotics, psychostimulants, treatments for alcohol addiction as naltrexone or acamprosate or baclofen, opioid agonist treatment as buprenorphine or methadone, lithium, anticonvulsants, other dopaminergic or serotonergic agents, inhibitors of UGT1A9 and 1A10, monoamine oxidase inhibitors (MAOIs), aldehyde dehydrogenase inhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs)).

Sponsors & Collaborators

• Brugmann University Hospital: lead

Study Sites (1)

Brugmann University Hospital

Brussels, Belgium

RECRUITING

Related Publications (2)

• Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, Rotrosen J, Tonigan JS, Worth L. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Oct 1;79(10):953-962. doi: 10.1001/jamapsychiatry.2022.2096.

  PMID: 36001306 BACKGROUND

• Vanderijst L, Hever F, Buot A, Daure C, Benoit J, Hanak C, Veeser J, Morgieve M, Campanella S, Kornreich C, Mallet L, Leys C, Noel X. Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial. BMC Psychiatry. 2024 Jan 26;24(1):77. doi: 10.1186/s12888-024-05502-y.

  PMID: 38279085 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Charles Kornreich, M.D. Ph.D.

  Brugmann University Hospital, Free University of Brussels

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laetitia Vanderijst, M.Sc.

CONTACT

02 477 22 33; laetitia.vanderijst@ulb.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Psychiatry

Model Details: Monocentric, randomized, double-blind, placebo-controlled, 1:1 parallel-group 7-month clinical trial comparing the effects of a high dose of psilocybin to those of a low dose of psilocybin (active placebo) provided within the context of a brief standardized psychotherapeutic intervention in 62 participants with severe alcohol use disorder.

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 7, 2023
• Study Start: February 15, 2024
• Primary Completion: December 15, 2025
• Study Completion (Estimated): June 15, 2026
• Last Updated: August 7, 2024

Record last verified: 2024-08

Locations

BE (1)