Clinical trial NCT04141501: Clinical and Mechanistic Effects of Psilocybin in Alcohol Addicted Patients
Official title: Phase II, Randomized, Double Blind, Placebo Controlled, Parallel Group, Single Center Study of Psilocybin Efficacy and Mechanism in Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Use Disorder
Keywords: Alcoholism
Psilocybin
Psychedelics
clinical efficacy
autobiographical memory
cue-reactivity exposure
placebo-controlled
proof-of-concept
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Schweizerischer Nationalfonds
First posted: 2019-10-28
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase II, randomized, double blind, placebo controlled, parallel group, single center study
Primary purpose: TREATMENT

Brief summary: Effects of serotonin 2A/1A receptor stimulation by psilocybin on alcohol addicted patients: a randomized double-blind placebo-controlled study

Detailed description: Two billion people globally consume alcohol, leading in 2016 to 2.8 million deaths (5.2% of all deaths) and 99.2 million Disability Adjusted Life Years (DALYs) lost (4.2% of all DALYs). Of all the diseases, conditions, and injuries attributable to alcohol use, alcohol use disorders (AUDs) create the largest health burden globally. However, approved pharmacological treatments for alcoholism are limited in their effectiveness. A recent proof of- concept study testing psilocybin in ten alcohol dependent patients provides encouraging efficacy results and safety data. The investigators, therefore, propose to test the efficacy of psilocybin for treating alcohol use disorder and study its underlying neurobiological mechanisms in a randomized, placebo controlled, double blind study. To evaluate effects of psilocybin on alcohol use behaviour, clinical symptoms, neurocognitive and emotional measures in patients with alcohol use disorder.

The present clinical trial aims at investigation the clinical and mechanistic effects of Psilocybin in Alcohol Addicted Patients.

Patients with alcohol use disorder who have undergone withdrawal treatment within the last 6 weeks will be investigated in a single-centre, double-blind, placebo-controlled, parallel-group design clinical trial contrasting the acute and persisting effects of psilocybin to those of placebo. Patients will be randomly assigned to psilocybin or placebo group with a 1:1 allocation ratio. The study comprises a total of 6 visits during 6 weeks and two follow-up online surveys (3 and 6 months after treatment). In addition, two follow-up surveys that can be completed from home will guarantee monitoring of long-lasting changes in symptomology and ensure all potential side-effects can be captured. On the treatment visit, a single dose of psilocybin (25mg) or placebo will be administered. Patients will be monitored until all effects have worn off.

Eligibility criteria: Inclusion Criteria:

* Informed Consent as documented by signature
* Right-handedness according to Oldfield (1971) perfomed during the telephone screening, laterality index ≥ 0.2
* DSM-IV-diagnosis of alcohol use disorder (based on clinical assessment and confirmed by the SCID Interview)
* Having undergone withdrawal treatment from alcohol use or have stopped consuming alcohol within 6 weeks prior to enrolment in the study
* Drug free from any psychotropic and serotonergic medication for at least five days before administration of the study drug or placebo
* No alcohol use between withdrawal treatment and administration of study drug or placebo
* Good physical health with no unstable medical conditions, as determined by medical history, physical examination, routine blood labs, electrocardiogram, urine analysis, and urine toxicology
* Normal level of language comprehension (German or Swiss-German)
* Willing to refrain from drinking caffeinated drinks during the testing days and from consuming psychoactive substances after enrolling in the study and for the remainder of the study
* Women of childbearing potential must be using an effective, established method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices. Note: female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
* Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions (driving is forbidden at drug treatment days)
* No further medication is allowed until visit 6, except for emergencies

Exclusion Criteria:

* Allergy, hypersensitivity, or other adverse reaction to previous use of psilocybin or other hallucinogens
* uncorrected Hypertension (assessed at screening day: higher than 139 systolic and 89 diastolic)
* Women who are pregnant or breast feeding
* Intention to become pregnant during the course of the study,
* Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases (Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential)
* Known or suspected non-compliance
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Previous enrolment into the current study
* Enrolment of the investigator, his/her family members, employees and other dependent persons
* Lifetime history of bipolar disorder (I, II, not otherwise specified) Lifetime history of schizophrenia, schizoaffective disorder, or psychosis not otherwise specified
* History of DSM-IV drug dependence other than alcohol (except for caffeine or nicotine) within two months prior to enrolment
* Comorbid Axis I anxiety and depression disorders diagnoses as well as post-traumatic stress disorder will be permitted if they do not require current treatment
* Family history of schizophrenia or schizoaffective disorder, or bipolar disorder type 1 (first or second degree relatives)
* Violent behaviour within last 2 years or history of suicidal behaviour
* Lifetime history of hallucinogen use on more than 10 occasions within last 10 years
* Getting psychotherapeutic or psychological treatment from third parties during the study is forbidden
* Abnormal electrocardiogram
* Any unstable illness as determined by history or laboratory tests
* BMI \<17 or \>30
* Uncorrected hypo- or hyperthyroidism
* Contraindications to magnetic resonance imaging (MRI safety form)
* During the study, new use or dose changes of already existing concomitant medication without prior informing the investigators is forbidden
* High risk of adverse emotional or behavioural reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behaviour, serious current stressors, lack of meaningful social support)
* Participation in another study with investigational drug within the 30 days preceding and during the present study
* Taking medications that are known to modulate uridine diphosphate glucuronosyltransferase enzyme
* Inhibitors of UGT1A9 and 1A10 should be discontinued at least five half-lives prior to the administration of psilocybin
* Monoamine oxidase and aldehyde or alcohol dehydrogenase inhibitors should be discontinued at least 5 half-lives prior to the dose of psilocybin

Primary outcomes:
measure: Changes in Time-Line Follow-Back
timeFrame: every day from baseline until 6 months after the intervention (primary endpoint: 4 weeks after administration, follow-up period 6 months)
measure: Relapse using Time-Line Follow-Back
timeFrame: Relapse will be compared between the placebo and psilocybin group in the time period four weeks after visit 3
Secondary outcomes:
measure: Brain
timeFrame: The MRI will be completed at baseline (visit 2, approx. 5 days prior), approx. 90 minutes after the administration of the investigational medicinal product (IMP), and following IMP-administration (approx. 4 weeks later).
measure: Empathy
timeFrame: five days before IMP-administration, one day post and approx. 4 weeks post intervention
measure: Blood sample: Neural profile analysis
timeFrame: At baseline, approx. five days before intervention
measure: Blood sample: Epigenetic analysis
timeFrame: At baseline (approx. five day before intervention), one day after the IMP-administration, and approx. 4 weeks after the IMP-administration
measure: Blood sample: Markers of alcohol use
timeFrame: This will be analysed at screening visit and approx. 4 weeks after the IMP-administration.
measure: Alcohol Self-Efficacy Scale
timeFrame: The questionnaire will be completed at screening (visit 1, approx. 14 days prior), baseline (visit 2, approx. 5 days prior), and post IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups)
measure: Penn Alcohol Craving Scale
timeFrame: The questionnaire will be completed at screening (visit 1, approx. 14 days prior), baseline (visit 2, approx. 5 days prior), directly before IMP administration, and post IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups)
measure: Snaith-Hamilton-Pleasure Scale (SHAPS)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).]
measure: Number of Heavy Drinking Days (HDDs)
timeFrame: 4 weeks after administration, and at 6 month follow-up
measure: Time to Relapse
timeFrame: 4 weeks after administration, and at 6 month follow-up
measure: Emotion-Regulation Questionnaire (ERQ)
timeFrame: The questionnaire will be completed at baseline (approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups)
measure: Savoring Believes Inventory (SBI)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).]
measure: Temporary Experience of Pleasure Scale (TEPS)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).]
measure: Quality of Life Scale (QOL)
timeFrame: It will be completed at baseline (approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups)
measure: Positive and Negative Affect Schedule (PANAS)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).
measure: Stundentagebuch, STEPP/STEPT
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).
measure: Hopelessness-Scale (HS-scale)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).
measure: Frankfurt Self-Concept Scale (FSKN)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).
measure: Beck Depression Inventory (BDI)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).
measure: Hamilton Anxiety Scale (HAMA)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).]
measure: The Stress Questionnaire (CQ)
timeFrame: The questionnaire will be completed at baseline (visit 2, approx. 5 days prior), and following IMP administration (1, approx. 14, approx. 28 days post-treatment and follow-ups).]
measure: Drinker Inventory of Consequences (DrInc)
timeFrame: The questionnaire will be completed at screening (visit 1, approx. 14 days prior to the IMP-administration), and following IMP administration (approx. 28 days post-treatment and follow-ups)
measure: Symptom Checklist (SCL-90-R)
timeFrame: The questionnaire will be completed at screening (visit 1, approx. 14 days prior to the IMP-administration), and following IMP administration (approx. 28 days post-treatment and follow-ups)
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: Psychiatrische Universitätsklinik Zürich
Study officials:
affiliation: Psychiatric University Clinic
name: Katrin Preller, Dr.
role: PRINCIPAL_INVESTIGATOR
References: