Ketamine plus real-time fMRI neurofeedback for alcohol use disorder

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

This trial will test whether ketamine combined with real-time fMRI neurofeedback helps adults with alcohol use disorder drink less.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Psychiatric University Hospital, Zurich (other)
• Locations: 1 site (Zurich)
• Trial ID: NCT06969937 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 trial gives adults with alcohol use disorder either ketamine or placebo together with real-time fMRI neurofeedback or a sham procedure to measure effects on drinking and brain chemistry. Investigators will compare intervention groups and track mean alcohol use per day and heavy drinking days one month after the last treatment. The study will measure changes in glutamatergic neurotransmission in the nucleus accumbens and relate those changes to cue-induced craving. The goal is to see whether ketamine-dependent modulation of glutamate and the addition of targeted neurofeedback produce clinical benefit or synergistic effects.

Who should consider this trial

Good fit: Adults aged 18–65 with DSM-IV alcohol use disorder who are motivated to reduce or stop drinking, fluent in German/Swiss-German, and medically stable would be ideal candidates.

Not a fit: People with current or lifetime psychotic disorders, recent ketamine or hallucinogen use, severe non-alcohol substance dependence, pregnancy, or unstable medical conditions are unlikely to qualify or benefit.

Why it matters

Potential benefit: If successful, the approach could reduce drinking and cravings by targeting glutamate-related brain circuits and offer a new treatment option for people with AUD.

How similar studies have performed: Previous randomized trials combining ketamine with behavioral interventions have shown reductions in alcohol use, but combining ketamine with real-time fMRI neurofeedback is a novel approach.

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.
* Taking medications that are known to modualte uridine diphosphate glucuronosyltransferase-enzyme
* Medication directly affecting glutamate signaling (e. g. anticonvulsant medication)
* Inhibitors of UGT1A9 and 1A10 should be discontinued at least five half-lives prior to the administration of ketamine.
* Monoamine oxidase and aldehyde or alcohol dehydrogenase inhibitors should be discontinued at least 5 half-lives prior to the dose of ketamine.
* Pregnancy or lactation
* Women of childbearing potential with no use of medically accepted contraceptive (e. g. condoms, contraceptive diaphragm, birth control pill, hormone injection, intrauterine device)
* BMI \< 17 or \> 35
* Allergy, hypersensitivity, or other adverse reaction to previous use of ketamine
* Contradictions to magnetic resonance imaging
* Concurrent participation in other clinical study

Where this trial is running

Zurich

• Psychiatric University Zurich, University of Zurich — Zurich, Switzerland (RECRUITING)

Study contacts

• Study coordinator: Marcus Herdener, PD Dr. med.

Conditions: Alcohol Abuse/Dependence, Alcohol Use Disorder, Alcoholism, Alcohol Dependence, Ketamine, Glutamate, Placebo-controlled, Neurofeedback Training