Clinical trial NCT05416229: Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder
Official title: The QUANTUM Trip Trial - Psilocybin-assisted Therapy for Reducing Alcohol Intake in Patients With Alcohol Use Disorder: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder
Keywords: psilocybin
alcohol dependence
addiction
randomized controlled trial
brain imaging
Lead sponsor: Psychiatric Centre Rigshospitalet
Sponsor class: OTHER
Collaborators: name: The Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet
First posted: 2022-06-13
Enrollment: 90
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-centre, randomised, double-blinded, placebo-controlled, 1:1 parallel-group clinical trial
Primary purpose: TREATMENT

Brief summary: Note: The trial is only eligible for citizens of Denmark.

The purpose of this project is to assess the treatment efficacy of a single high dose of psilocybin administered within a protocol of psychological support to patients diagnosed with alcohol use disorder (AUD).

Detailed description: To establish efficacy, we will investigate a single dose of psilocybin versus placebo in a randomised, double-blinded, placebo-controlled 12 weeks clinical trial. 90 patients, aged 20-70 years, diagnosed with alcohol use disorder and treatment seeking will be recruited from the community via advertisement and referrals from general practitioners and hospital units. The psilocybin or placebo is administered within a protocol of psychological support before, during and after the dosing. Outcome assessments will be carried out one, four, eight- and 12 weeks post dosing. The primary outcome is reduction in the percentage of heavy drinking days from baseline to follow-up at 12 weeks. Key secondary outcomes include 1) phosphatidyl-ethanol as an objective biomarker for alcohol consumption 2) plasma psilocin, the active metabolite, to establish a possible therapeutic range and 3) the acute subjective drug experience as a possible predictor of treatment outcome. Furthermore, we will investigate the neurobiological underpinnings of the possible treatment effects by use of functional magnetic resonance brain imaging one week post dosing.

Eligibility criteria: Inclusion Criteria:

* Bodyweight of 50-110 kg
* AUD according to DSM-5 criteria and alcohol dependence according to ICD-10.
* AUD Identification Test (AUDIT) ≥ 15.
* ≥ 5 heavy drinking days in the past 28 days prior to inclusion.

Exclusion Criteria:

* Current or previously diagnosed with any psychotic disorder or bipolar affective disorder.
* Immediate family member with a diagnosed psychotic disorder.
* History of delirium tremens or alcohol withdrawal seizures.
* History of suicide attempt or present suicidal ideation at screening.
* Withdrawal symptoms at screening (\>nine on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) (43).
* Present or former severe neurological disease including trauma with loss of consciousness \> 30 min.
* Impaired hepatic function (alanine transaminase \>210/135 units/l men/women)
* Cardiovascular disease defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris, myocardial infarction within the last 12 months or uncontrolled hypertension (systolic blood pressure \>165 mmHg, diastolic blood pressure \>95 mmHg).
* Present or former abnormal QTc (\>450/470 ms men/women).
* Treatment with disulfiram, naltrexone, acamprosate and nalmefene within 28 days of inclusion.
* Treatment with any serotonergic medication or drugs within one month prior inclusion.
* Any oOther active substance use disorders (except nicotine) defined as a Drug Use Disorder Identification Test score \>six/two (men/women) and investigator's clinical evaluation.
* Women who are pregnant, breastfeeding, or intend to become pregnant or are not using adequate contraceptive measures considered highly effective (44).
* Unable to speak or understand Danish.
* Any other condition that the clinician estimates can interfere with trial participation.

Primary outcomes:
measure: Change in percentage of heavy drinking days
timeFrame: Baseline to week 12
Secondary outcomes:
measure: Change in total alcohol consumption
timeFrame: Baseline to week 12
measure: Change in days of abstinence
timeFrame: Baseline to week 12
measure: Change in phosphatidyl-ethanol (PEth)
timeFrame: Baseline to week 12
measure: Change in Alcohol Use Disorders Identification Test (AUDIT)
timeFrame: Baseline to week 12
measure: Change in Penn Alcohol Craving Scale (PACS) score
timeFrame: Baseline to week 12
measure: Change in Alcohol Abstinence Self-efficacy Scale (AASE) score
timeFrame: Baseline to week 12
measure: Change in Fagerstrom Test for Nicotine Dependence (FTND)
timeFrame: Baseline to week 12
measure: Change in Drug Use Disorders Identification Test (DUDIT)
timeFrame: Baseline to week 12
measure: Change in Major Depression Inventory (MDI)
timeFrame: Baseline to week 12
measure: Change in Short-Form 36 (SF-36)
timeFrame: Baseline to week 12
measure: Change in Mindful Attention Awareness Scale (MAAS)
timeFrame: Baseline to week 12
measure: Change in Acceptance and Action Questionnaire (AAQ)
timeFrame: Baseline to week 12
measure: Change in NEO-Personality Inventory (NEO-PI=
timeFrame: Baseline to week 12
measure: Persisting Effects Questionnaire (PEQ)
timeFrame: Week 12
measure: Neuroplasticity and inflammation
timeFrame: Baseline to week 12
measure: Subjective effects of psilocybin: Subjective Drug Intensity (SDI)
timeFrame: 0-6 hours post dosing
measure: Pharmacokinetics- and dynamics of psilocybin
timeFrame: 0 - 6 hours post dosing
measure: Subjective effects of psilocybin: Mystical Experience Questionnaire (MEQ)
timeFrame: Completed once the effects are fully subsided or at least 6 hours after dosing
measure: Subjective effects of psilocybin: 5-Dimensional Altered State of Consciousness scale (5D-ASC)
timeFrame: Completed once the effects are fully subsided or at least 6 hours after dosing
measure: Subjective effects of psilocybin: Ego Dissolution Inventory (EDI)
timeFrame: Completed once the effects are fully subsided or at least 6 hours after dosing
measure: Subjective effects of psilocybin: Emotional Breakthrough Inventory (EBI)
timeFrame: Completed once the effects are fully subsided or at least 6 hours after dosing
measure: Subjective effects of psilocybin: Awe Experience Scale (AWE-S)
timeFrame: Completed once the effects are fully subsided or at least 6 hours after dosing
measure: Brain imaging
timeFrame: 1 week post dosing
Other outcomes:
measure: Role of the Music I
timeFrame: before and after dosing
measure: Role of the Music II
timeFrame: week 4
measure: Treatment expectancies
timeFrame: Baseline
measure: Optional long-term follow-ups
timeFrame: week 26 and week 52
Locations:
city: Frederiksberg
country: Denmark
facility: Psychiatric Center Copenhagen, Frederiksberg Hospital
Study officials:
affiliation: Psychiatric Center Copenhagen, Frederiksberg Hospital
name: Anders Fink-Jensen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jensen ME, Stenbaek DS, Juul TS, Fisher PM, Ekstrom CT, Knudsen GM, Fink-Jensen A. Psilocybin-assisted therapy for reducing alcohol intake in patients with alcohol use disorder: protocol for a randomised, double-blinded, placebo-controlled 12-week clinical trial (The QUANTUM Trip Trial). BMJ Open. 2022 Oct 14;12(10):e066019. doi: 10.1136/bmjopen-2022-066019.