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

NCT ID: NCT06125054

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-05

Study Completion Date

2026-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Cocaine is the most frequently used stimulant worldwide, and its consumption rate in Europe indicates a continuing upward trend. Cocaine use is associated with great harms for affected individuals, their families, and the society. Unfortunately, until today no pharmacotherapy has been approved for the treatment of cocaine use disorder (CUD) due to lack of efficacy of tested compounds.

The investigators therefore propose, to use latest advancements in proton magnetic resonance spectroscopy (1H-MRS) and real time functional magnetic resonance imaging neurofeedback training (rt-fMRI NFT) to develop a neurobiologically informed experimental approach for an individualized and integrated pharmaco-psychotherapy that has the potential to open new avenues for the treatment of CUD, and in addition, to be transferable to other neuropsychiatric conditions.

To improve the efficacy of psychotherapeutic interventions in individuals with CUD, the investigators recently developed an rt-fMRI NFT paradigm based on reward imagery to specifically modify maladaptive reward sensitivity by self-regulating the brain's reward circuits.

Furthermore, using a 1H-MRS technique, the investigators recently demonstrated that a disturbed glutamate homeostasis in the nucleus accumbens (NAcc), an important hub in the brain's reward system, characterizes cue-induced craving in CUD. This indicates that urgently needed novel pharmacotherapies for addiction treatment should target the glutamatergic system.

Thus, to restore the glutamate homeostasis and to boost learning effect of the reward imagery training, the investigators propose to combine reward imagery rt- fMRI NFT with the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, which has direct effects both on glutamatergic signaling and neuroplasticity and has shown therapeutic potential to reduce cocaine craving and cocaine us.

The investigators anticipate a) restoration of the glutamate homeostasis in the NAcc b) changes in maladaptive reward sensitivity resulting from rt-fMRI NFT and c) synergistic effects of the pharmacological and the psychotherapeutic effect due to the ketamine-induced neuroplasticity that might open a window of opportunity for imagery-based learning. The investigators hypothesize that these neurobiological adaptions induced by the described interventions underlie their therapeutic effects on cocaine craving and use.

The effects of ketamine and reward imagery rt-fMRI NFT in individuals with CUD will be tested in a randomized, placebo-controlled, double blind, parallel group study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cocaine Use Disorder Cocaine Dependence

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, placebo-controlled, double blind, parallel group, single center study
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

rt-fMRI NFT / Placebo

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

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

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

real-time fMRI neurofeedback training

Intervention Type 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

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

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

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

real-time fMRI neurofeedback training

Intervention Type 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.

sham NFT / Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

sham real-time fMRI neurofeedback training

Intervention Type 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

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.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

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

sham real-time fMRI neurofeedback training

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ketamine

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

real-time fMRI neurofeedback training

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.

Intervention Type BEHAVIORAL

sham real-time fMRI neurofeedback training

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.

Intervention Type BEHAVIORAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

0.9% saline solution

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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)

Exclusion Criteria

* 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)
* 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)
* Increased intracranial pressure
* Medication directly affecting glutamate signaling (e. g. anticonvulsant medication)
* Any unstable psychoactive medication (no changes in compounds within last 4 weeks before start of study)
* 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\>35
* Allergy, hypersensitivity, or other adverse reaction to previous use of ketamine
* Contradictions to magnetic resonance imaging
* Concurrent participation in other clinical study
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Zurich

OTHER

Sponsor Role collaborator

University of Vienna

OTHER

Sponsor Role collaborator

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role collaborator

Dr. med. Marcus Herdener

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Dr. med. Marcus Herdener

Dr. med.

Responsibility Role SPONSOR_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Psychiatric University Hospital Zurich, University of Zurich

Zurich, Canton of Zurich, Switzerland

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Switzerland

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Marcus Herdener, PD Dr. med.

Role: CONTACT

Phone: +41583845810

Email: [email protected]

Etna Engeli, Dr.

Role: CONTACT

Phone: +41583842771

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Marcus Herdener, PD Dr. med.

Role: primary

Etna Engeli, Dr.

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40999531 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Co-Boost_PUK_2022-01859

Identifier Type: -

Identifier Source: org_study_id