Cannabidiol for reducing drinking in alcohol use disorder and modifying the effects of alcohol on the brain and the liver

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Le Vinatier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

26 Dec 2024 → 16 Mar 2026

Decision date (initial)

2024-11-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS PHRCN

External identifiers

EU CT number

2024-517751-13-01

EudraCT number

2019-004740-30

ClinicalTrials.gov

NCT05159830

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The primary objective of the CARAMEL study is to compare the reduction
in alcohol drinking between CBD and placebo (PCB), in a population of
patients with AUD and heavy drinking level at baseline (i.e., 12 standard
drinks (sd)/day or more).
The drinking reduction level will be defined by the total consumption in
the 28 days prior to inclusion, minus the total consumption of the 28 last
days of the study (weeks 8 to 12).

Secondary objectives 9

1. Between-group comparison of other important drinking outcomes, i.e., total percentage of heavy drinking days, total percentage of days with no drinking, difference in craving scores between inclusion (V0) and end of treatment visit (V4).
2. Between-group comparison of the difference between inclusion (V0) and end of treatment visit (V4) observed in other clinical parameters (i.e., anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) score).
3. Between-group comparison in the reduction of the Controlled Attenuation Parameter (CAP) which measures liver steatosis using transient ultra-sound elastography, between V0 and V4.
4. Between-group comparison of alcohol-induced biological liver parameters (GGT, CDT, SGOT, SGPT, bilirubin) at V4.
5. Between-group comparison of alcohol-induced biological parameters (PEth) at V4.
6. Between-group comparison of the reduction 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).
7. 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.
8. Between-group comparison of the improvement in neuropsychological measures between V0 and V4.
9. Between-group comparison of the drinking level difference between last visit (V5) and end of treatment visit (V4).

Conditions and MedDRA coding

Psychiatric disorders

Regulatory references

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Being aged 18 years, or more
2. Comprendre le français
3. Having read the information procedure and signed the informed consent sheet
4. Being affiliated with health insurance
5. DSM-5 criteria for AUD (all stages) (American Psychiatric Association, 2013)
6. 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 16

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be the total consumption of alcohol (in standard-drinks, sd) in the 28 last days (week 8 to week 12) of the study, using the 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 endpoints 14

1. Percentages of heavy drinking days (i.e., 6 standard-drinks or more) during the study period.
2. Difference (i.e., inclusion minus end of study) in alcohol craving scores using the OCDS.
3. Difference (i.e., inclusion minus end of study) in alcohol use disorder scores using the AUDIT-C.
4. Difference (i.e., inclusion minus end of study) in GGT levels.
5. Difference (i.e., inclusion minus end of study) in CDT levels.
6. Difference (i.e., inclusion minus end of study) in PEth levels.
7. Difference (i.e., inclusion minus end of study) in anxiety and depression (HADS) scores.
8. Difference (i.e., inclusion minus end of study) in self-confidence to resist, quality of life (SF12v2), stigmatization, sleep quality (PSQI) scores.
9. Difference (i.e., inclusion minus end of study) in CAP scores using ultra-sound electrography.
10. Difference (i.e., inclusion minus end of study) in steatosis score using MRI morphometric assessment of fat composition of the liver.
11. Difference (i.e., inclusion minus end of study) in steatosis score using SRM assessment of lipid peaks in the liver.
12. Brain map of difference (i.e., inclusion minus end of study) in grey matter volumes in corticostriatal-limbic circuits.
13. Brain difference (i.e., inclusion minus end of study) in cortical thickness of insula, superior temporal gyrus, dorso-lateral prefrontal cortex and anterior cingulate cortex.
14. Difference (i.e., inclusion minus end of study) in attentional, memory and executive functions abilities using neuropsychological testing.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Le Vinatier

Sponsor organisation

Centre Hospitalier Le Vinatier

Address

Auvergne Rhone Alpes, 95 Boulevard Pinel, Bp 30039 95 Boulevard Pinel Bp 30039

City

Bron Cedex

Postcode

69678

Country

France

Scientific contact point

Organisation

Centre Hospitalier Le Vinatier

Contact name

VIAL Véronique

Public contact point

Organisation

Centre Hospitalier Le Vinatier

Contact name

VIAL Véronique

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications