This placebo-controlled, double-blind, parallel-group interventional trial (n=120) aims to explore the effects of combining ketamine with real-time functional magnetic resonance imaging (fMRI) neurofeedback training in individuals with cocaine use disorder (CUD).
Led by Dr. Med. Marcus Herdener from the Psychiatric University Hospital, Zurich, the study seeks to answer several key questions: Firstly, whether there is a positive, significant effect on the percentage of cocaine use days with both interventions combined and separately; secondly, if there is a significant transfer effect of the neurofeedback training; and thirdly, whether there is a significant, ketamine-dependent change in glutamate levels in the nucleus accumbens.
Cocaine use disorder poses significant societal challenges, with no approved pharmacotherapy available due to the lack of efficacy of tested compounds. The study leverages advancements in proton magnetic resonance spectroscopy (1H-MRS) and real-time fMRI neurofeedback training to develop an individualized and integrated pharmaco-psychotherapy approach. Participants will undergo real-time fMRI neurofeedback training based on reward imagery to modify maladaptive reward sensitivity by self-regulating the brain’s reward circuits. Additionally, ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist with therapeutic potential in reducing cocaine craving and use, will be administered to restore glutamate homeostasis and enhance learning effects of the reward imagery training.
The trial employs a randomized, placebo-controlled, double-blind, parallel group design, where participants will be assigned to four intervention groups. These groups will receive either real-time neurofeedback training or sham training alongside either ketamine or placebo administration. Various outcome measures will be assessed, including the decrease in proportion of cocaine use days, changes in fMRI signal of neurofeedback training, and alterations in accumbal glutamate levels. Secondary outcome measures encompass changes in urine cocaine and metabolites, cocaine craving, severity of cocaine use disorder, and other psychological factors. The study commenced on February 5, 2024, with an estimated completion date in March 2026.
Trial Details
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.NCT Number NCT06125054
Sponsors & Collaborators
University of ZurichWithin the Department of Psychiatry, Psychotherapy and Psychosomatics at the University of Zurich, Dr Mialn Scheidegger is leading team conducting psychedelic research and therapy development.