Can a single dose of psilocybin reduce alcohol intake in patients with alcohol use disorder?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

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

1 Sep 2023 → ongoing

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Helse Fonden · Novo Nordisk Fonden · Lundbeck Fonden

External identifiers

EU CT number

2024-517497-17-01

EudraCT number

2020-000829-55

ClinicalTrials.gov

NCT05416229

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacokinetic

The aim of this research project is to evaluate the effect of a single administration of the 5-HT2A receptor agonist Psilocybin on heavy drinking days from baseline to follow-up after 12 weeks in patients with alcohol use disorder, in a randomized, double-blinded, placebo-controlled clinical trial.

Conditions and MedDRA coding

Alcohol Use Disorder

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age of 20-70 years (both included)
2. Body weight of 60-95 kg (both included)
3. Diagnosed with AUD according to DSM-5 criteria and alcohol dependence according to ICD-10
4. Alcohol Use Disorder Identification Test (AUDIT) ≥ 15
5. ≥ 5 heavy drinking days defined as alcohol consumption over 60 g of alcohol per day (men) or 48 g of alcohol per day (women) in the past 28 days prior to inclusion, measured by TLFB

Exclusion criteria 18

1. Personal or first-degree relatives with current or previous diagnosis within psychotic spectrum disorders or bipolar disorder.
2. History of delirium tremens or alcohol withdrawal seizures.
3. History of suicide attempt or present suicidal ideation.
4. Withdrawal symptoms at inclusion, defined as a score higher than 9 on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar).
5. Present or former severe neurological disease including head trauma with loss of consciousness > 30 min.
6. Impaired hepatic function (liver transaminases >3 times upper normal limit).
7. Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months.
8. Abnormal electrocardiogram
9. mpaired renal function (eGFR < 50 ml/min).
10. Uncontrolled hypertension (systolic blood pressure >165 mmHg, diastolic blood pressure >95 mmHg).
11. Pharmacotherapy against AUD including disulfiram, naltrexone, acamprosate and nalmefene or treatment with any of these compounds within 28 days prior to inclusion.
12. Treatment with any serotonergic medication or any use of serotonergic psychedelics within 1 month prior to inclusion.
13. Any other active substance use defined as a Drug Use Disorder Identification Test score > 6/2 (m/w) and substance use disorder based on investigator's clinical evaluation, except for nicotine.
14. Women of childbearing potential who are pregnant, breastfeeding or have intention of becoming pregnant or are not using adequate contraceptive measures considered highly effective.
15. Hypersensitivity to the active substance or to any of the excipients.
16. Only for patients undergoing brain scans: Contraindications for undergoing an fMRI scan (magnetic implants, pacemaker, claustrophobia etc.)
17. Unable to speak and/or understand Danish.
18. Any condition that the investigator feels would interfere with trial participation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of heavy drinking days during the last 28 days. A heavy drinking day is defined as a day with an excess intake of 60/48 grams (men/women) of alcohol per day. Data will be registered via TLFB.

Secondary endpoints 21

1. Total alcohol consumption (gram/day) during the last 28 days. Data will be registered via TLFB.
2. Percentage of days without any alcohol consumption during the last 28 days. Data will be registered via TLFB.
3. Penn Alcohol Craving Scale (PACS) score.
4. Alcohol Use Disorders Identification Test (AUDIT) score.
5. Drug Use Disorders Identification Test (DUDIT) score.
6. Alcohol Abstinence Self-efficacy (AASE) score.
7. Quality of life (SF-36) score.
8. Major Depression Inventory (MDI) score.
9. Mindful Attention Awareness Scale (MAAS) score.
10. NEO Personality Inventory score.
11. Acceptance and Action Questionnaire score.
12. Fagerström Test for Nicotine Dependence (FTND) score.
13. Phosphatidyl-ethanol (PEth).
14. Liver parameters gamma-glutamyltransferase (GGT), alanine aminotransferase (ALAT) and mean corpuscular volume (MCV).
15. Brain-derived neurotrophic factor (BDNF).
16. Markers of inflammation (TNF-a and IL-6).
17. Pharmacokinetic properties of plasma psilocin.
18. Key phenomena of the acute subjective experience assessed by questionnaires including the Mystical Experience Questionnaire (MEQ30), 11-Dimensional Altered State of Consciousness (11D-ASC)51, Emotional Breakthrough Inventory (EBI), Ego-dissolution Inventory (EDI), The Awe Experience Scale (AES) and the Experience of Music (EM) as well as qualitative analysis of video/audio recordings (before, during and after the psilocybin session).
19. Changes in emotional response to music as rated by the Geneva Emotional Music Scale (GEMS) and qualitative descriptions obtained by semi-structured interviews.
20. Persisting Effects Questionnaire (PEQ) score
21. Post dosing fMRI analysis including differences in functional connectivity during resting state and task-related activity between treatment groups.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Nordre Fasanvej 57, 1st Floor Entrance 2 1st Floor Entrance 2

City

Frederiksberg

Postcode

2000

Country

Denmark

Scientific contact point

Organisation

Psykiatrisk Center Kobenhavn

Contact name

Mathias Ebbesen Jensen

Public contact point

Organisation

Psykiatrisk Center Kobenhavn

Contact name

Anders Fink-Jensen

Third parties 1

Sponsor responsibilities

Article 77 compliance

Region Hovedstaden

Contact point sponsor

Region Hovedstaden

Article 77 implementation

Region Hovedstaden

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 8 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