Ketamine and Neurofeedback-Training: Effects on Neuroplasticity in Cocaine Addiction

NCT06125054 | Recruiting Phase 2

• 1 other identifier: Co-Boost_PUK_2022-01859
• Study Type: interventional
• Target: 120
• 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 in individuals with cocaine use disorder. The main questions the investigators aim to answer are:

• Can the investigators observe a positive, significant effect on percentage of cocaine use days of both interventions combined as well as stand alone interventions?
• Is there a significant transfer effect of the neurofeedback training?
• Is there a significant, ketamine-dependent change in glutamate levels in the nucleus accumbens? Participants will be given ketamine and a realtime fMRI neurofeedback training. Both interventions are placebo-controlled. The investigators will compare the four intervention groups to investigate the effects of the stand-alone effects of the intervention and the combination of it.

Conditions

Cocaine Use Disorder; Cocaine Dependence

Keywords

Cocaine; Cocaine Use; Ketamine; Reward Sensitivity; Glutamate; Placebo-controlled; Therapeutic effects; Mechanistic effects; Neurofeedback Training; realtime fMRI

Outcome Measures

Primary Outcomes (3)

• Decrease in proportion of cocaine use days

  Between-group comparison of proportion of cocaine use days measured with Time-Line Follow-Back questionnaire for cocaine use on follow-up visit (t3).

  Between 5 and 7 weeks after baseline (the first intervention visit)

• Changes in fMRI signal of neurofeedback training

  Signal changes assessed with fMRI between the non-neurofeedback run 1 on Interention Visit I (t1) and run 3 on Intervention Visit II (t2).

  Between 1 and 2 weeks after baseline (the first neurofeedback training)

• Changes in accumbal glutamate levels

  Baseline and acute accumbal glutamate levels assessed with 1H-MRS on Intervention Visit I (t1).

  Before and during infusion (same day)

Secondary Outcomes (16)

• Changes in urine cocaine and cocaine metabolites

  Baseline (screening visit) up to 19 weeks later (Follow-up Visit)

• Cocaine craving

  From baseline (screening visit) until 38 weeks later (Follow-up Survey)

• Severity of cocaine use disorder

  From baseline (screening visit) until 38 weeks later (Follow-up Survey)

• Current motivation to change cocaine use behaviour

  From baseline (screening visit) until 38 weeks later (Follow-up Survey)

• Hedonic capacity

  From baseline (screening visit) until 38 weeks later (Follow-up Survey)

Study Arms (4)

rt-fMRI NFT / Placebo

EXPERIMENTAL

Participants get real time neurofeedback based on an experimental regions' activity and receive a 0.9% saline solution (i.v.) over 40 minutes.

Drug: Placebo; Behavioral: real-time fMRI neurofeedback training

rt-fMRI NFT / Ketamine

EXPERIMENTAL

Participants get real time neurofeedback based on an experimental regions' activity and receive 0.71mg ketamine (i.v.) per kilogram bodyweight.

Drug: Ketamine; Behavioral: real-time fMRI neurofeedback training

sham NFT / Placebo

PLACEBO COMPARATOR

Participants get a real time neurofeedback based on a control regions' activity, which serves as a sham region and receive a 0.9% saline solution (i.v.) over 40 minutes.

Drug: Placebo; Behavioral: sham real-time fMRI neurofeedback training

sham NFT / Ketamine

EXPERIMENTAL

Participants get a real time neurofeedback based on a control regions' activity, which serves as a sham region and receive 0.71mg ketamine (i.v.) per kilogram bodyweight.

Drug: Ketamine; Behavioral: sham real-time fMRI neurofeedback training

Interventions

Ketamine DRUG

single dose of ketamine (0.71mg/kg bodyweight i.v. over 40 minutes)

rt-fMRI NFT / Ketamine; sham NFT / Ketamine

Placebo DRUG

single dose of placebo (0.9% saline solution i.v. over 40 minutes)

Also known as: 0.9% saline solution

rt-fMRI NFT / Placebo; sham NFT / Placebo

real-time fMRI neurofeedback training BEHAVIORAL

Real-time fMRI based neurofeedback over 20 minutes where participants are instructed to perform reward imagery. The feedback is based on an experimental region. The training is repeated three times.

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

sham real-time fMRI neurofeedback training BEHAVIORAL

Sham real-time fMRI neurofeedback training over 20 minutes where participants are instructed to perform reward imagery. The feedback is based on a control region. The training is repeated three times.

sham NFT / Ketamine; sham NFT / Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Informed Consent as documented by signature
• Male and female cocaine users 18 to 55 years of age
• diagnostic and statisical manual (DSM)-5 diagnosis of CUD
• Willingness to comply with the study protocol as explained by investigator
• Normal level of language comprehension (German or Swiss-German)

You may not qualify if:

• 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
• Current severe alcohol use disorder
• Current severe cannabis use disorder
• Current moderate or severe stimulant use disorder (other than cocaine)
• Current moderate or severe benzodiazepine use disorder
• Current opioid use disorder
• First-degree relatives with psychotic disorders
• Beck Depression Inventory Score greater than 25
• 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)

Sponsors & Collaborators

• Dr. med. Marcus Herdener: lead
• University of Zurich: collaborator
• University of Vienna: collaborator
• University of Campania Luigi Vanvitelli: collaborator

Study Sites (1)

Psychiatric University Hospital Zurich, University of Zurich

Zurich, Canton of Zurich, 8032, Switzerland

RECRUITING

Related Publications (1)

• Trippel AS, Gubser LP, Engeli EJE, Conradi J, Haugg A, Zoelch N, Herdener M. Co-Boost: boosting and guiding neuroplasticity by combining ketamine with neurofeedback-assisted learning-towards an individualised and integrated pharmaco-psychotherapy for cocaine addiction: study protocol for a randomised, placebo-controlled, double-blind, parallel-group, single-centre trial. Trials. 2025 Sep 25;26(1):354. doi: 10.1186/s13063-025-08982-9.

  PMID: 40999531 DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Ketamine; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. med.

Model Details: Randomized, placebo-controlled, double blind, parallel group, single center study

Study Record Dates

• First Submitted: October 26, 2023
• First Posted: November 9, 2023
• Study Start: February 5, 2024
• Primary Completion: December 1, 2025
• Study Completion: March 1, 2026
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

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

Locations

CH (1)