Cocaine Dependence Clinical Trial
— Co-BoostOfficial title:
Boosting and Guiding Neuroplasticity by Combining Ketamine With Neurofeedback-assisted Learning - Towards an Individualized and Integrated Pharmaco-psychotherapy for Cocaine Addiction
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.
Status | Recruiting |
Enrollment | 120 |
Est. completion date | March 2026 |
Est. primary completion date | December 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 55 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Switzerland | Psychiatric University Hospital Zurich, University of Zurich | Zürich |
Lead Sponsor | Collaborator |
---|---|
Dr. med. Marcus Herdener | University of Campania "Luigi Vanvitelli", University of Vienna, University of Zurich |
Switzerland,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | |
Primary | Changes in fMRI signal of neurofeedback training | Signal changes assessed with fMRI between the non-neurofeedback runs on Interention Visit I (t1) and Intervention Visit II (t2). | Between 1 and 2 weeks after baseline (the first neurofeedback training) | |
Primary | 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 | Changes in urine cocaine and cocaine metabolites | Changes in cocaine and cocaine metabolites via urine analysis as objectified measure of cocaine use. | Baseline (screening visit) up to 19 weeks later (Follow-up Visit) | |
Secondary | Cocaine craving | Changes in cocaine craving score assessed by the Obsessive Compulsive Cocaine Use Scale, ranging from 0 to 56, where higher scores indicate more problematic behavior and thoughts. | From baseline (screening visit) until 38 weeks later (Follow-up Survey) | |
Secondary | Severity of cocaine use disorder | Changes in severity of cocaine use disorder assessed by the Obsessive Compulsive Cocaine Use Scale, ranging from 0 to 56, where higher scores indicate more problematic behavior and thoughts. | From baseline (screening visit) until 38 weeks later (Follow-up Survey) | |
Secondary | Current motivation to change cocaine use behaviour | Changes in current motivation to change cocaine use behaviour assessed by an visual analogue scale ranging from 0 to 30 where higher scores indicate a higher motivation to change. | From baseline (screening visit) until 38 weeks later (Follow-up Survey) | |
Secondary | Hedonic capacity | Changes in hedonic capacity measured by the Trait Hedonic Capacity Scale, ranging from 16 to 80, where a higher score indicates a higher hedonic capacity. | From baseline (screening visit) until 38 weeks later (Follow-up Survey) | |
Secondary | Experience of pleasure across different domains | Changes in the experience of pleasure across different domains assessed by the Domains of Pleasure Scale, ranging from 0 to 210 where a higher score indicates a higher experience of pleasure. | From baseline (screening visit) until 38 weeks later (Follow-up Survey) | |
Secondary | Emotion regulation skills | Changes in emotion regulation skills measured with the Negative Mood Regulation expectancies Scale, ranging from 30 to 150 where higher scores indicate higher emotion regulation skills. | Baseline (screening visit) and up to 19 weeks later (Follow-up Visit) | |
Secondary | Depressive symptoms | Changes in depressive symptoms measured with the Beck Depression Inventory. The scale ranges from 0 to 63 where higher scores indicate more severe depressive symptoms. | Baseline (screening visit), up to 14 weeks later (Intervention Visit II), and up to 19 weeks later (Follow-up Visit) | |
Secondary | Perceived stress | Changes in perceived stress assessed with a subscale of the Stress & Coping Inventory, ranging from 21 to 147 where higher scores indicate higher perceived stress. | Baseline (screening visit), up to 19 weeks later (Follow-up Visit), and up to 38 weeks later (Follow-up Survey) | |
Secondary | Self-esteem | Changes in self-esteem assessed with the Rosenberg Self-esteem Scale, ranging from 0 to 30 where higher scores indicate a higher self-esteem. | Baseline (screening visit), up to 14 weeks later (Intervention Visit II), up to 19 weeks later (Follow-up Visit), and up to 38 weeks later (Follow-up Survey) | |
Secondary | Self-efficacy, optimism, and pessimism | Changes in Self-efficacy, optimism, and pessimism assessed with the Questionnaire for Self-efficacy, Optimism, and Pessimism (KSWOP-9), ranging from 9 to 36 where higher scores indicate higher self-efficacy, optimism, and pessimism, respectively. | Baseline (screening visit), up to 14 weeks later (Intervention Visit II), up to 19 weeks later (Follow-up Visit), and up to 38 weeks later (Follow-up Survey) | |
Secondary | Subjective effects of ketamine infusion | Assess the acute subjective effects of the infusion with the Five-Dimension Altered State of Consciousness Questionnaire (5D-ASC), where the global score and each of the 11 subscales range from 0 to 100 and higher scores indicate the occurence of altered states of consciousness. | 2 hours post infusion | |
Secondary | Effects of ketamine infusion on mystic experiences | Assess the acute subjective effects of the infusion with the Hood's Mysticism Scale, ranging from 20 to 100 where higher scores indicate the occurence of mystic experiences. | 2 hours post infusion | |
Secondary | Sustained changes in accumbal glutamate levels | Assess sustained effects of the infusion and the neurofeedback training on baseline accumbal glutamate levels with 1H-MRS. | Baseline (pre infusion, Intervention Visit I) and up to 2 weeks after infusion and neurofeedback training (Intervention Visit II) | |
Secondary | Glutamate levels during craving paradigm | Assess the effects of the infusion and the neurofeedback training on glutamate levels measured by 1H-MRS during a craving paradigm. | Up to 2 weeks post infusion and neurofeedback training | |
Secondary | Functional connectivity | Changes in functional connectivity measured with fMRI during resting state | Baseline (Intervention Visit I) and up to 2 weeks later (Intervention Visit II) | |
Secondary | Changes in Brain Derived Neurotrophic Factor | Assess changes in Brain Derived Neurotrophic Factor (BDNF) through blood analysis before and after the infusion. | 0.5 hours pre infusion and 2 hours post infusion |
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