A Trial to Investigate the Effects of Cannabidiol Plus Naltrexone on Alcohol Craving in Patients With Alcohol Dependence

Official title

ICONICplus - Randomized, Double-blind, Placebo-controlled Trial to Investigate the Effects of Cannabidiol Plus Naltrexone on Cue-Induced Alcohol Craving in Alcohol Dependence

Overview

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.

Interventions

• Drug Cannabidiol capsules
  800mg (trial arm 1) or 1200mg (trial arm 2) Cannabidiol capsules will be administered daily over the course of 14 days.
• Drug Naltrexone (drug)
  All participants will receive 50mg Naltrexone daily as oral tablet throughout the study.
• Drug Placebo
  Placebo capsules matching the cannabidiol capsules will be administered daily.

Primary outcome measures

• Obsessive Compulsive Drinking Scale (OCDS-G) [Time frame: The difference of alcohol craving between baseline (visit 2) and 14 days after the first treatment visit (visit 5) will serve as primary endpoint.]

Secondary outcome measures (12)

• Obsessive Compulsive Drinking Scale (OCDS-G) [Time frame: 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)]
• Subjective quality of life index [Time frame: 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) [Time frame: Difference from baseline (visit 2, day -2) of depressive symptoms to end of treatment (visit 5, day 14)]
• State Trait Anxiety Inventory (STAI) [Time frame: Difference from baseline (visit 2, day -2) of depressive symptoms to end of treatment (visit 5, day 14)]
• Patient reported outcomes (PRO) [Time frame: 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 [Time frame: On visit 3 (day 1 of treatment) and visit 5 (day 14, end of treatment)]
• Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: 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 frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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)]

Eligibility criteria

Inclusion criteria

• Age between 18 and 70 years
• Patients meeting the diagnosis of an alcohol dependence according to the ICD-10
• Patients reporting alcohol craving as symptom of AD according to the ICD10 symptom definition
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrollment in the study)
• Consent to random assignment
• For women with childbearing potential (WOCBP) and males with partners with CBP, use of a highly effective birth control method until one month after last IMP administration (see Appendix 1) and negative pregnancy test

Exclusion criteria

• Current psychotic or bipolar disorder or current severe depressive episode with suicidal ideations
• Current treatment with any of the following substances: Any investigational medicinal product, Opioid-containing Analgesics, Anti-obesity drugs, Anticonvulsants, Opioid-containing Antidiarrheal Agents, Antineoplastics, Antipsychotics (exception: episodic use of melperone, prothipendyl, pipamperone, promethazine and quetiapine are allowed), Antidepressants (exception: allowed, when being taken in stable dose for a minimum of 14 days prior to enrolment and/or doxepine in low doses \[max. 75mg daily\]), Opioid-containing Cough/cold agents, Systemical Steroids, Other anti-craving (e.g. Acamprosate) or aversive medication (e.g. disulfiram), THC- or CBD-containing medication, Antiretroviral medication (e.g., Efavirenz), Xanthines (e.g., Theophylline), General anesthetics (e.g., propofol), Hypericum perforatum, Antibiotics (e.g., Rifampin, Clarithromycin, Erythromycin)
• Positive drug screening (amphetamines/ecstasy, opiates, cocaine, barbiturates)
• Pregnancy, lactation or breastfeeding
• Current severe somatic comorbidities: severe liver cirrhosis \[CHILD B or C\] or epilepsy determined by medical history
• Patients with elevated transaminase levels (AST or ALT) above three times the upper limit normal (ULN) value with elevated bilirubin levels above twice the ULN value
• History of hypersensitivity to the investigational medicinal product CBD and/or Naltrexone (trade names: Adepend, Naltrexon-Hcl neuraxpharm, Naltrexonhydrochlorid Accord) or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product CBD and/or Naltrexone
• Participation in other clinical trials or observation period of competing clinical trials, respectively.
• Acute suicidal tendency or acute endangerment of self and others

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Germany · 2 centers

• Psychiatric Centre North Baden (PZN) — Wiesloch
• Central Institute of Mental Health — Mannheim

Publications

• 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 Op PMID 40803733

Identifiers

NCT: NCT06845124 · CIMH ICONICplus 25 · 2024-518164-12-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗