Clinical TrialAlcohol Use Disorder (AUD)KetamineKetaminePlaceboRecruiting

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

This Phase II, randomised, placebo-controlled, double-blind, parallel-group single-centre trial (n=75) will assess the effects of a single IV ketamine infusion (0.8 mg/kg) combined with real-time fMRI neurofeedback versus sham NFT and placebo in people with alcohol use disorder.

Target Enrollment
75 participants
Study Type
Phase II interventional
Design
Randomized, triple Blind

Detailed Description

Randomised, placebo-controlled, double-blind, parallel-group Phase II single-centre study evaluating a single IV ketamine infusion (0.8 mg/kg) alone or combined with closed-loop rt-fMRI neurofeedback in adults with alcohol use disorder (n=75).

Primary mechanistic outcomes assess glutamatergic signalling in the nucleus accumbens and ketamine-dependent changes in glutamate; neuroplasticity markers (BDNF) and ketamine metabolism will also be measured.

Clinical endpoints include mean alcohol use per day and heavy drinking days one month after the last intervention; rt-fMRI NFT consists of a 25-minute closed-loop training to downregulate cue-induced cravings.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

rt-fMRI NFT / Ketamine

experimental

Real-time fMRI neurofeedback with single IV ketamine 0.8 mg/kg.

Interventions

  • Ketamine0.8 mg/kg
    via IV• single dose• 1 doses total
  • Compound
    via Other• concurrent

    Closed-loop real-time fMRI neurofeedback (25 minutes) to downregulate cue-induced cravings.

sham NFT / Ketamine

experimental

Sham neurofeedback with single IV ketamine 0.8 mg/kg.

Interventions

  • Ketamine0.8 mg/kg
    via IV• single dose• 1 doses total
  • Compound
    via Other• concurrent

    Sham neurofeedback based on control region activity.

rt-fMRI NFT / Placebo

experimental

Real-time fMRI neurofeedback with single placebo (0.9% NaCl) infusion.

Interventions

  • Placebo
    via IV• single dose

    0.9% NaCl infusion (placebo).

  • Compound
    via Other• concurrent

    Closed-loop real-time fMRI neurofeedback (25 minutes).

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion 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

  • Exclusion Criteria:
  • History of DSM-IV severe drug dependence other than alcohol (except for caffeine or nicotine) and any opioid 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 arrhythmias, severe pulmonary secretions, glaucoma, congestive heart failure or angina, significant renal or hepatic impairment)
  • Acute infection (e.g. pulmonary or upper respiratory tract infection)
  • Insufficiently 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 modulate 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
  • Contraindications to magnetic resonance imaging
  • Concurrent participation in other clinical study

Study Details

Locations

Psychiatric University Zurich, University of Zurich — Zurich, Switzerland

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