Clinical trial NCT05159830: Cannabidiol for Reducing Drinking in Alcohol Use Disorder
Official title: Cannabidiol for Reducing Drinking in Alcohol Use Disorder and Modifying the Effects of Alcohol on the Brain and the Liver: a Phase 2 Clinical Trial.-The CARAMEL Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder
Lead sponsor: Hôpital le Vinatier
Sponsor class: OTHER
First posted: 2021-12-16
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: CARAMEL is a phase-2, national, multi-site, interventional (category 1), double-blind, randomized, placebo-controlled trial, conducted in 76 subjects.
Primary purpose: TREATMENT

Brief summary: The non-psychotomimetic cannabis compound cannabidiol (CBD) has been found effective for reducing alcohol drinking in mice. Moreover, other experimental studies have found that CBD reduced alcohol-induced steatosis in the liver, and reduced alcohol-related injury in the brain. Despite these promising results from animal data, no human study has been conducted yet in alcohol use disorder (AUD).

Detailed description: CBD has several potential therapeutic prospects in AUD. Preclinical studies now support the potential of CBD for drinking reduction in AUD subjects. Moreover, other experimental studies have found that CBD reverse the alcohol-induced steatosis process in the liver. These two experimental effects need a translational confirmation in humans through an explanatory phase 2 study. In addition, CBD could also exert neuroprotective effects that reduce the deleterious effects of alcohol on the brain. In both the liver and the brain, the idiosyncratic anti-inflammatory effects of CBD could thus strengthen the overall harm reduction allowed by drinking reduction in AUD ± ALD patients.

CBD deserves an exploratory study assessing whether the different therapeutic prospects in AUD are warranted. Moreover, because CBD is extracted from cannabis, and even if it is a CB1 antagonist with no psychotomimetic effects and no reported potential for abuse, the first pieces of evidence in AUD should confirm that CBD is safe in AUD subjects.

The CARAMEL study is a phase-2 clinical trial on 76 subjects, which aims to investigate the efficacy of CBD on reducing alcohol drinking, as well as the potential of CBD for restraining alcohol-induced brain and liver injuries, and confirm the good safety profile of CBD.

Eligibility criteria: Inclusion Criteria:

* Being aged 18 - 65 years
* Being fluent in French
* Having read the information procedure and signed the informed consent sheet.
* Being affiliated with health insurance.
* DSM-5 criteria for AUD (all stages) (American Psychiatric Association, 2013)
* Average drinking level of at least 12 standard-drinks (120g of ethanol) per day over the month prior to inclusion (i.e., a total alcohol consumption of 336 standard-drinks during the 28-day assessment period prior to inclusion), using the A-TLFB.

Exclusion Criteria:

* At least one day of abstinence (no alcohol drinking) during the month prior to inclusion
* Criteria for liver cirrhosis (Child-Pugh B or C)
* DSM-5 criteria for schizophrenia, schizoaffective disorder, or bipolar disorder, using the MINI 7.0.2.
* Current suicidality, using the MNI 7.0.2
* Lifelong history of suicide attempts
* Lifelong history or current DSM-5 criteria for substance use disorder (other than alcohol or nicotine) using the MINI 7.0.2.
* Any detected use of cannabis or any other cannabinoid within 60 days prior to screen
* Patients with transaminase elevations greater than 3 times upper the limit of normal and bilirubin greater than 2 times upper the limit of normal.
* Impaired medical condition (investigator's decision)
* Pregnancy, lactation, or insufficient contraceptive measure (precautionary measure) (See 5.2 for acceptable birth control methods)
* Patients with cancer, HIV, pulmonary arterial hypertension, epilepsy and with rifampicin, St. John's wort, Mammalian target of rapamycin (mTOR), calcineurin inhibitors or triazole antifungal agents like posaconazole, fluconazole... .
* History of vascular accident and/or cardiac arrhythmias and/or myocardial infarction
* Patients receiving acamprosate, naltrexone, disulfiram, nalmefene, topiramate, baclofen for AUD within 30 days prior to screening.
* MRI contraindication: pacemaker, insulin pump, heart metal valve, cochlear implant...
* Known hypersensitivity to the active principle (cannabidiol) or excipients (sucralose, menthol, mannitol).
* Person under tutorship or curatorship.

Primary outcomes:
measure: the total consumption of alcohol (in standard-drinks, sd) in the 28 last days (week 8 to week 12) of the study, using the Alcohol Timeline Followback (A-TLFB) daily self-report of alcohol drinking
timeFrame: Five months
Secondary outcomes:
measure: Difference (i.e., inclusion minus end of study) in alcohol craving scores using the Obsessive Compulsive Drinking Scale (OCDS).
timeFrame: Five months
measure: Difference in alcohol use disorder scores using the Alcohol Use Disorders Identification Test scale (AUDIT-C).
timeFrame: Five months
measure: Difference in anxiety and depression Hospital Anxiety and Depression Scale (HADS)
timeFrame: Five months
measure: Difference in Controlled Attenuation Parameter (CAP) scores
timeFrame: Five months
measure: Change in steatosis scores between V0 and V4, using Proton Density Fat Fraction (PDFF) estimated on the structural liver based on Chemical Shift Encoding-MRI (CSE-MRI) and MR Spectroscopy (MRS).
timeFrame: Five months
measure: Between-group comparison of recovery of grey matter integrity in corticostriatal-limbic circuits, between V0 and V4, using MRI Voxel Based Morphometry (VBM) and cortical thickness measures.
timeFrame: Five months
Other outcomes:
Locations:
city: Bron
country: France
facility: Centre Hospitalier Le Vinatier
state: Auvergne Rhone Alpes
Study officials:
affiliation: Centre Hospitalier le Vinatier
name: Benjamin ROLLAND, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: