Ketamine and Neurofeedback as Combined Therapeutic Interventions to Target Glutamatergic Neurotransmission in Alcohol Use Disorder

NCT06969937 | Recruiting Phase 2 DMC

• 1 other identifier: 2024-02294
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn about the effects of the combination of ketamine and realtime functional magnetic resonance imaging (fMRI) neurofeedback training on the treatment of individuals with alcohol use disorder (AUD). The main questions the investigators aim to answer are:

• Can the investigators observe a positive, significant therapeutic effect by comparing changes in alcohol use via i) mean alcohol use per day, ii) heavy drinking days one month after the last treatment intervention?
• Are changes in glutamatergic neurotransmission in the nucleus accumbens related to cue-induced cravings in individuals with AUD?
• Is there a significant, ketamine-dependent change in glutamate levels in the nucleus accumbens? Participants will be given ketamine or placebo and real-time fMRI neurofeedback (rt-fMRI NFT) or sham rt-fMRI NFT. The investigators will compare three intervention groups to investigate the effects of the stand-alone effects as well as potential synergies between the combination of pharmacological and non-pharmacological intervention.

Conditions

Alcohol Abuse/Dependence; Alcohol Use Disorder (AUD); Alcoholism

Keywords

Alcohol Use Disorder; Alcoholism; Alcohol Dependence; Ketamine; Glutamate; Placebo-controlled; Neurofeedback Training; Realtime fMRI; Therapeutic effects; Mechanistic effects

Outcome Measures

Primary Outcomes (2)

• Change in mean alcohol use per day

  Change in mean alcohol use per day. Alcohol use is measured via a combination of the digital app and the Timeline Follow-Back Questionnaire.

  Starting immediately after the intervention visit 2 and ending 4 weeks later (integration visit).

• Change in heavy drinking days

  Change in heavy drinking days. Defined as five or more standard units of alcohol in a day for a man and four or more standard units of alcohol in a day for a woman. Alcohol use is measured via a combination of the digital app and the Timeline Follow-Back Questionnaire.

  Starting immediately after the intervention visit 2 and ending 4 weeks later (integration visit).

Secondary Outcomes (19)

• Changes in glutamat levels during craving

  During the intervention visit 1a and 1 week later during the intervention visit 2.

• Changes in Brain Derived Neurotrophic Factor

  During the intervention visit 2 at baseline 30 minutes before and 2 hours after infusion start.

• Individual variations in ketamine pharmacokinetics

  During the intervention visit 2 at baseline, 45 minutes, 1 hour 30 minutes before, and 2 hours 30 minutes after infusion start.

• Predictive value of baseline rs-fMRI for treatment response

  Between 1 and 2 weeks after baseline (screening visit) during the intervention visit 1a.

• Changes in alcohol use in blood alcohol metabolites

  At baseline (screening visit) and 4 weeks later (integration visit).

Study Arms (3)

rt-fMRI NFT / Ketamine

EXPERIMENTAL

Participants get real time neurofeedback based on an experimental regions' activity and receive 0.8 mg ketamine (i.v.) per kilogram bodyweight.

Drug: Ketamine; Behavioral: Real-time fMRI Neurofeedback Training

sham rt-fMRI NFT / Ketamine

EXPERIMENTAL

Participants get a real time neurofeedback based on a control regions' activity, which serves as a sham region and receive 0.8 mg ketamine (i.v.) per kilogram bodyweight.

Drug: Ketamine; Behavioral: Sham Neurofeedback Training/ Ketamine

rt-fMRI NFT / Placebo

EXPERIMENTAL

Participants get real time neurofeedback based on an control regions' activity and receive a 0.9% NaCL infusion (placebo).

Behavioral: Real-time fMRI Neurofeedback Training; Drug: Placebo

Interventions

Ketamine DRUG

A single dose of ketamine 0.8 mg ketamine (i.v.) per kilogram bodyweight

rt-fMRI NFT / Ketamine; sham rt-fMRI NFT / Ketamine

Real-time fMRI Neurofeedback Training BEHAVIORAL

Participants will undergo a closed-loop rt-fMRI paradigm over 25 minutes. Participants will be instructed to use strategies to downregulate cue-induced cravings. The Intensity of cues will adjust based on the participants neural activity in response to cues. This dynamic feedback mechanism allows for personalized training aimed at improving the participant's ability to manage cravings.

rt-fMRI NFT / Ketamine; rt-fMRI NFT / Placebo

Placebo DRUG

Single dose of placebo (0.9% NaCl infusion)

rt-fMRI NFT / Placebo

Sham Neurofeedback Training/ Ketamine BEHAVIORAL

Participants get a real time neurofeedback based on a control regions' activity, which serves as a sham region and receive 0.8 mg ketamine (i.v.) per kilogram bodyweight. The use of sham-NFT allows for a rigorous assessment of the specific effects of combined rt-fMRI NFT and ketamine by controlling for non-specific factors such as expectancy effects or the therapeutic context.

sham rt-fMRI NFT / Ketamine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent as documented by signature
• In- and outpatients aged 18 to 65 years of all sexes.
• DSM-IV diagnosis of alcohol use disorder (mild - severe).
• Motivation to reduce or stop alcohol use
• Normal level of language comprehension (German or Swiss-German)
• Good physical health with no unstable medical conditions
• Participants of childbearing potential must use an effective and established method of contraception for the entire study duration
• Comply with the study protocol as explained by investigator

You may not qualify if:

• History of DSM-IV severe drug dependence other than alcohol (except for caffeine or nicotine) and any opiod use disorder within two months prior to enrolment.
• Hallucinogen and ketamine use 3 months prior to study participation (including regular microdosing).
• Alcohol withdrawal symptoms at any of the treatment visits (V2 and V3) (CIWA-Ar Scale \>9).
• Current or lifetime psychotic disorders
• History of severe substance-induced psychosis
• Current or lifetime bipolar I or II disorders
• Current suicidality
• Previous suicide attempts during the last 2 years
• High risk of adverse emotional and behavioral reactions
• Unmedicated or unstable hypertension
• Severe illness (e. g. myocardial ischemia or arrythmias, severe pulmonary secretions, glaucoma, congestive heart failure or angina, significant renal or hepatic impairment)
• Acute infection (e. g. pulmonary or upper respiratory tract infection)
• Insufficient treated or uncorrected hyperthyroidism
• Severe central nervous system related traumas or disorders (e. g. stroke, cerebral trauma with loss of consciousness over more than 24h, epilepsy)
• During the study, new use or dose changes of already existing concomitant medication without prior informing the investigators.

Sponsors & Collaborators

• Dr. med. Marcus Herdener: lead
• University of Zurich: collaborator

Study Sites (1)

Psychiatric University Zurich, University of Zurich

Zurich, 8032, Switzerland

RECRUITING

MeSH Terms

Conditions

Alcoholism

Interventions

Ketamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Marcus Herdener, PD Dr. med.

CONTACT

+41583845810; marcus.herdener@bli.uzh.ch

Etna Engeli, Dr.

CONTACT

+41583842771; etna.engeli@bli.uzh.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Head of Center for Addictive Disorders

Model Details: Phase II, randomised, placebo-controlled, double blind, parallel group, single centre study investigating ketamine and neurofeedback as combined therapeutic interventions to target glutamatergic neurotransmission in alcohol use disorder.

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: May 14, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After the publication of our data.

Locations

CH (1)