Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2024-518164-12-00 | EU Trial (CTIS) Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Heidelberg University | OTHER |
| Heinrich-Heine University, Duesseldorf | OTHER |
| German Federal Ministry of Education and Research | OTHER_GOV |
Not provided
Not provided
Not provided
Not provided
Alcohol addiction (AD) is a chronic relapsing disorder with currently limited pharmacological treatment options. Alcohol craving, a hallmark symptom of AD that drives relapse in patients, is only insufficiently treated by existing medication. One promising new compound for the treatment of alcohol craving in AD is Cannabidiol (CBD), which showed beneficial effects on alcohol craving in preliminary clinical studies. Additionally, CBD seems to be a particularly promising candidate for enhancing the effects of established medication, specifically Naltrexone (NTX), an opioid-antagonist, which is approved for AD treatment, due to the synergistic effects of the combination of Cannabidiol plus Naltrexone on alcohol consumption that were shown by preclinical studies. The proposed three-armed, 1:1:1 randomized, double-blind, placebo-controlled parallel group, multicentric phase II trial seeks to test the putative synergistic effects of combined CBD (800mg) + oral NTX (50mg) against CBD (1200mg) + oral NTX (50mg) against Placebo + oral NTX (50mg) on alcohol craving (primary outcome) in male and female patients with AD that suffer from high alcohol craving. The trial seeks to test the effects of the innovative combination of CBD plus NTX against Placebo plus NTX on alcohol craving over a 14-day treatment period, which is embedded in a standardized addiction treatment program according to current treatment guidelines, in order to estimate the added value of treatment with CBD on alcohol craving. Quality of life and neurobiological and biochemical markers for craving will serve as secondary outcomes, because they show strong associations to treatment outcome and relapse risk. Collection and analysis of follow-up data (28 days, 42 days, 105 days, 196 days) will be performed to determine whether treatment effects relate to patient outcome.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cannabidiol (800mg) + Naltrexone | Experimental | All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the experimental group of trial arm 1, patients will receive a dose of 800mg Cannabidiol (CBD) daily over the course of 14 days during in-patient treatment. |
|
| Cannabidiol (1200mg) + Naltrexone | Experimental | All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the experimental group of trial arm 2, patients will receive a dose of 1200mg Cannabidiol (CBD) daily over the course of 14 days during in-patient treatment. |
|
| Placebo + Naltrexone | Active Comparator | All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the comparator group of trial arm 3, patients will receive placebo capsules daily over the course of 14 days during in-patient treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cannabidiol capsules | Drug | 800mg (trial arm 1) or 1200mg (trial arm 2) Cannabidiol capsules will be administered daily over the course of 14 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Obsessive Compulsive Drinking Scale (OCDS-G) | The alcohol craving will be assessed at separate time points before and after Cannabidiol administration using the Obsessive Compulsive Drinking Scale. The Obsessive Compulsive Drinking Scale consists of 14 items, each rated on a 5-point Likert scale (0-4), resulting in scores from 0 to 40, with higher scores indicating higher craving. | The difference of alcohol craving between baseline (visit 2) and 14 days after the first treatment visit (visit 5) will serve as primary endpoint. |
| Measure | Description | Time Frame |
|---|---|---|
| Obsessive Compulsive Drinking Scale (OCDS-G) | The alcohol craving will be assessed at separate time points before and after Cannabidiol administration using the Obsessive Compulsive Drinking Scale. The Obsessive Compulsive Drinking Scale consists of 14 items, each rated on a 5-point Likert scale (0-4), resulting in scores from 0 to 40, with higher scores indicating higher craving. | Differences from baseline (visit 2, day -2) of Obsessive Compulsive Drinking Scale craving scores to visits 4 (day 7, i.e., 7 days after the first treatment visit) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Patrick Bach, Prof. Dr. Dr. | Contact | +49-621-1703-0 | patrick.bach@zi-mannheim.de | |
| Sina Vetter, M.Sc. | Contact | +49-621-1703-0 | Sina.Vetter@zi-mannheim.de |
| Name | Affiliation | Role |
|---|---|---|
| Patrick Bach, Prof. Dr. Dr. | Central Institute of Mental Health, Mannheim | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Psychiatric Centre North Baden (PZN) | Not yet recruiting | Wiesloch | Baden-Wurttemberg | 69168 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40803733 | Derived | Vetter S, Weinberg J, Thomas BC, Kirchner M, Thalmann P, Klose C, Pfisterer M, Kolsch T, Oesterle S, Vollstaedt-Klein S, Koopmann A, Lenz B, Kiefer F, Link T, Bach P. Investigation of the combined effects of cannabidiol plus naltrexone on alcohol craving in alcohol dependence: study protocol of a phase II randomised, double-blind, placebo-controlled, parallel-group trial - ICONICplus Trial. BMJ Open. 2025 Aug 12;15(8):e106348. doi: 10.1136/bmjopen-2025-106348. |
Not provided
Not provided
Individual de-identified data will be shared, specifically individual participant data that underlie the results of the trial (i.e. primary outcome data [OCDS-G scores]) will be made available with a respective data dictionary. Secondary Outcome data (e.g. fMRI data) will be made available on aggregated group level (e.g. for the purpose of meta-analyses). Related documents, specifically the study protocol, statistical analysis plan and analytic code will be shared in open-access online repositories. Aggregated data will be made available to publicly accessible repositories (Neurosynth.org), e.g. for the purpose of meta-analyses.
Data will be available upon publication of the results until 3 years after that.
Individual data will be shared with researchers who provide a methodologically sound proposal (sent to the Principal Investigator/Study Chair of the Trial).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Naltrexone (drug) | Drug | All participants will receive 50mg Naltrexone daily as oral tablet throughout the study. |
|
| Placebo | Drug | Placebo capsules matching the cannabidiol capsules will be administered daily. |
|
| Subjective quality of life index | Quality of life will be assessed using the World Health Organization Quality of life questionnaire (WHO-QOL-BREF) scores at separate time points before and after Cannabidiol administration. The World Health Organization Quality of life questionnaire is an instrument that can assess patients' global health status independently of disease across 4 health domains and consists of 26 items rated on a 5-point Likert scale (1-5). To calculate the score, items 3, 4, 26 have to be inverted. Scores for each domain (Physical Health, Psychological Health, Social Relationships, Environment) are calculated, that range from 4 to 20. Higher scores indicate better quality of life, with the overall score reflecting a person's general well-being. | Differences from baseline (visit 2, day -2) of Quality of life (WHO-QOL-BREF scores) to end of treatment (visit 5, day 14) and follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196). |
| Beck Depression Inventory (BDI-II) | The depressive symptoms will be assessed at separate time points before and after Cannabidiol administration using the Beck Depression Inventory (BDI-II). The Beck Depression Inventory (BDI-II) is a 21-item self-rating inventory that measures characteristic attitudes and symptoms of depression. Each Item is rated on a 4-point Likert scale (0-3). The total score ranges from 0 to 63, with higher scores indicating more severe depressive symptoms. | Difference from baseline (visit 2, day -2) of depressive symptoms to end of treatment (visit 5, day 14) |
| State Trait Anxiety Inventory (STAI) | The state and trait anxiety will be assessed at separate time points before and after Cannabidiol administration using the State Trait Anxiety Inventory. The State Trait Anxiety Inventory (STAI) is a 20-item self-report questionnaire that assesses state anxiety and trait anxiety via two subscales: the State Anxiety Scale (STAI-S) and the Trait Anxiety Scale (STAI-T), each consisting of 20 items. Each item is rated on a 4-point Likert scale (1-4). A sumscore has to be calculated for each subscale, ranging from 20 to 80 each, with higher scores indicating higher levels of anxiety. | Difference from baseline (visit 2, day -2) of depressive symptoms to end of treatment (visit 5, day 14) |
| Patient reported outcomes (PRO) | The patient reported outcomes will be assessed at separate time points before and after Cannabidiol administration using a set of items assessing effects of the treatment as well as treatment burden on a five-point Likert scale (0 to 4) with higher values indicating more positive effects. | On visit 3 (day 1 of treatment), visit 4 (day 7 of treatment), visit 5 (day 14, end of treatment) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196) |
| CBD plasma levels | The CBD plasma levels will be determined at separate time points before and after Cannabidiol administration to detect effects of active intervention on blood plasma levels. (Only participants enrolled at CIMH study site). | On visit 3 (day 1 of treatment) and visit 5 (day 14, end of treatment) |
| Adverse Events (AEs) and Serious Adverse Events (SAEs) | Rate of adverse events and serious adverse events. | On visit 3 (day 1 of treatment), visit 4 (day 7 of treatment), visit 5 (day 14, end of treatment) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196) |
| Time to relapse | Time from baseline (visit 2, day -2) to relapse to alcohol use (i.e. any alcohol use) (in days), assessed using the Form-90 semi-structured interview (Timeline Follow Back). | On visit 5 (day 14, end of treatment) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196) |
| Cumulative alcohol consumption during the follow-up period | Cumulative alcohol consumption (in grams alcohol) during the follow-up period of 182 days (+/- 7 days), assessed using the Form-90 semi-structured interview (Timeline Follow Back). | On visit 5 (day 14, end of treatment) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196) |
| Percent heavy drinking days during the follow-up period | Percent heavy drinking days during the follow-up period of 182 days (+/- 7 days), assessed using the Form-90 semi-structured interview (Timeline Follow Back). | On visit 5 (day 14, end of treatment) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196) |
| Average weekly alcohol consumption during the follow-up period | Average weekly alcohol consumption assessed via smartphone-based e-diary every 7 days during the follow-up period of 182 days (+/- 7 days) (optional, only for patients that agree to use the study-specific app). | Every 7 days during the follow-up period of 182 days (+/- 7 days), starting after visit 5, i.e., end of treatment (day 14) and continuing until visit 9, i.e., end of follow up (day 196) |
| Maximum weekly craving during the follow-up period | Maximum weekly craving assessed via smartphone-based e-diary every 7 days during the follow-up period of 182 days (+/- 7 days) (optional, only for patients that agree to use the study-specific app). | Every 7 days during the follow-up period of 182 days (+/- 7 days), starting after visit 5, i.e., end of treatment (day 14) and continuing until visit 9, i.e., end of follow up (day 196) |
| Neural Brain Activation during functional magnetic resonance imaging | Differences from baseline of neural brain activation to visit 5, measured using the blood oxygenated level dependent (BOLD) response, during presentation of alcohol cues, during the presentation of natural reward cues, during inhibition of motor responses, during presentation of emotional faces and neutral shapes and functional connectivity during resting state (only for patients enrolled at CIMH study site). | Differences from baseline (visit 2, day -2) to visit 5 (day 14, end of treatment) |
| Alcohol Craving during functional magnetic resonance imaging | Differences from baseline of alcohol craving (visual analogue scale) during the functional magnetic resonance imaging (fMRI) to visit 5 (only for patients enrolled at CIMH study site). | Differences from baseline (visit 2, day -2) to visit 5 (day 14, end of treatment) |
| Response Times during functional magnetic resonance imaging | Differences in response times (i.e., time taken to respond) during functional magnetic resonance imaging (fMRI) from baseline to visit 5 (only for patients enrolled at CIMH study site). | Differences from baseline (visit 2, day -2) to visit 5 (day 14, end of treatment) |
| Rates of Errors during functional magnetic resonance imaging | Differences in rates of errors during functional magnetic resonance imaging (fMRI) from baseline to visit 5 (only for patients enrolled at CIMH study site) | Differences from baseline (visit 2, day -2) to visit 5 (day 14, end of treatment) |
| Rates of Correct Responses during functional magnetic resonance imaging | Differences in rates of correct responses during functional magnetic resonance imaging (fMRI) from baseline to visit 5 (only for patients enrolled at CIMH study site) | Differences from baseline (visit 2, day -2) to visit 5 (day 14, end of treatment) |
| Omission Rates during functional magnetic resonance imaging | Differences in omission rates (i.e., rate of failure to respond when a response is expected) during functional magnetic resonance imaging (fMRI) from baseline to visit 5 (only for patients enrolled at CIMH study site) | Differences from baseline (visit 2, day -2) to visit 5 (day 14, end of treatment) |
| Central Institute of Mental Health | Recruiting | Mannheim | 68159 | Germany |
|
| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D002185 | Cannabidiol |
| D009271 | Naltrexone |
| D004364 | Pharmaceutical Preparations |
| ID | Term |
|---|---|
| D002186 | Cannabinoids |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
Not provided
Not provided