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Cannabidiol for Reducing Drinking in Alcohol Use Disorder (CARAMEL)

Primary Purpose

Alcohol Use Disorder

Status

Not yet recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Cannabidiol Cap/Tab

Placebo Cap/Tab

About this trial

This is an interventional treatment trial for Alcohol Use Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Centre Hospitalier Le Vinatier

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cannabidiol (CBD)

PLACEBO (PCB)

Arm Description

CBD Group from 20mg x 2/day up to 600mg/day

PCB Group from 20mg x 2/day up to 600mg/day

Outcomes

Primary Outcome Measures

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

The difference between the total alcohol consumption during 28 days preceding the study, and the 28 last days of the study, will be compared between the two groups.

Secondary Outcome Measures

Difference (i.e., inclusion minus end of study) in alcohol craving scores using the Obsessive Compulsive Drinking Scale (OCDS).

Inclusion minus end of study using the OCDS. The Obsessive Compulsive Drinking Scale (OCDS) is a 14-item questionnaire that measures an individual's alcohol use and his/her attempts to control his/her drinking. Each item is scored on a scale from 0 to 4.Obsessive subscale is the summation of items 1-6.Compulsive subscale is the summation of items 7-14.

Difference in alcohol use disorder scores using the Alcohol Use Disorders Identification Test scale (AUDIT-C).

inclusion minus end of study The Alcohol Use Disorders Identification Test (AUDIT-C) is an alcohol screen that can help identify patients who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence). Probable misuse: score > 4 for men and > 3 for women. Probable dependence: score > 10 regardless of sex.

Difference in anxiety and depression Hospital Anxiety and Depression Scale (HADS)

Inclusion minus end of study Each answer corresponds to a number. By adding these numbers, we obtain a total score per column (anxiety and depression). If the score of a column is greater than or equal to 11, it means that the subject suffers from anxiety or depression

Difference in Controlled Attenuation Parameter (CAP) scores

Inclusion minus end of study Using ultra-sound electrography which measures liver steatosis using transient ultra-sound elastography, between V0 and V4

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).

Inclusion minus end of study

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.

Inclusion minus end of study

Full Information

NCT ID

NCT05159830

First Posted

September 20, 2021

Last Updated

April 17, 2023

Sponsor

Hôpital le Vinatier

1. Study Identification

Unique Protocol Identification Number

NCT05159830

Brief Title

Cannabidiol for Reducing Drinking in Alcohol Use Disorder

Acronym

CARAMEL

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

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

September 1, 2023 (Anticipated)

Primary Completion Date

September 30, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hôpital le Vinatier

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alcohol Use Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

CARAMEL is a phase-2, national, multi-site, interventional (category 1), double-blind, randomized, placebo-controlled trial, conducted in 76 subjects.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

PANAXIA Pharmaceutical Industries Ltd will produce tablets of Cannabidiol and Placebo of similar galenic form. They will be responsible for the pharmaceutical analyses of the product. Eurofins-LC2 will import the tablets after authorization from the ANSM, and will relabeled individual vials for each participant, and regular dispatching into the hospital pharmacy. Local hospital pharmacies will be in charge to deliver treatment individual vials to the investigators for dispensing.

Allocation

Randomized

Enrollment

76 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cannabidiol (CBD)

Arm Type

Experimental

Arm Description

CBD Group from 20mg x 2/day up to 600mg/day

Arm Title

PLACEBO (PCB)

Arm Type

Placebo Comparator

Arm Description

PCB Group from 20mg x 2/day up to 600mg/day

Intervention Type

Drug

Intervention Name(s)

Cannabidiol Cap/Tab

Intervention Description

The CBD dosing used in the CARAMEL study will start at 40mg/d up to 600 mg/d. Sublingual tablet contain 20 mg of CBD. 20 mg because our supplier does not have a more highly dosed tablet.

Intervention Type

Drug

Intervention Name(s)

Placebo Cap/Tab

Intervention Description

Placebo of similar cannabidiol galenic form

Primary Outcome Measure Information:

Title

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

Description

The difference between the total alcohol consumption during 28 days preceding the study, and the 28 last days of the study, will be compared between the two groups.

Time Frame

Five months

Secondary Outcome Measure Information:

Title

Difference (i.e., inclusion minus end of study) in alcohol craving scores using the Obsessive Compulsive Drinking Scale (OCDS).

Description

Time Frame

Five months

Title

Difference in alcohol use disorder scores using the Alcohol Use Disorders Identification Test scale (AUDIT-C).

Description

Time Frame

Five months

Title

Difference in anxiety and depression Hospital Anxiety and Depression Scale (HADS)

Description

Time Frame

Five months

Title

Difference in Controlled Attenuation Parameter (CAP) scores

Description

Inclusion minus end of study Using ultra-sound electrography which measures liver steatosis using transient ultra-sound elastography, between V0 and V4

Time Frame

Five months

Title

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).

Description

Inclusion minus end of study

Time Frame

Five months

Title

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.

Description

Inclusion minus end of study

Time Frame

Five months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mathieu CHAPPUY, PhD

Phone

00 33 4 37 91 50 75

mathieu.chappuy@chu-lyon.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Véronique VIAL

Phone

00 33 4 37 91 55 31

veronqiue.vial@ch-le-vinatier.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benjamin ROLLAND, MD, PhD

Organizational Affiliation

Centre Hospitalier le Vinatier

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier Le Vinatier

City

Bron

State/Province

Auvergne Rhone Alpes

ZIP/Postal Code

69678 cedex

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Cannabidiol for Reducing Drinking in Alcohol Use Disorder

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