CBD-OH - Cannabidiol as an add-on treatment during inpatient alcohol cessation in patients with severe alcohol use disorder: a Phase II trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Psychological Phenomena [F02]

Trial duration

3 Jul 2024 → ongoing

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

[DGOS - Ministry of Higher Education and Research] : PHRC National_18-0777

External identifiers

EU CT number

2024-518455-28-00

EudraCT number

2023-000158-87

ClinicalTrials.gov

NCT05860699

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To increase abstinence maintenance rate at week 6 of the study (1 month after discharge of the scheduled alcohol withdrawal inpatient stay).

Secondary objectives 6

1. To assess the safety of 10 days of up to 900 mg of cannabidiol as an add-on to usual care in the specific population of patients with severe alcohol use disorder during inpatient alcohol cessation
2. - In case of relapse, reducing alcohol use after discharge up to week 6 of the study
3. - To reduce alcohol withdrawal symptoms during inpatient alcohol cessation
4. - To reduce anxiety symptoms during inpatient alcohol cessation
5. - In a sub-group of patients: describe CBD plasmatic rate and test if it is correlated with side-effects and/or efficacy
6. - In the sub-group of patients with co-occuring cannabis use, reducing cannabis use after discharge up to week 6 of the study

Conditions and MedDRA coding

Patients with severe Alcohol Use Disorder (according to DSM 5) at entry of a scheduled inpatient alcohol cessation attempt

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1) Patients hospitalized for a scheduled alcohol inpatient cessation
2. 2) Aged 18-75 years old
3. 3) Meeting DSM 5 criteria for severe AUD
4. 4) Willing to participate
5. 5) Signing a written informed consent
6. 6) Patients with current social insurance
7. 7) For childbearing age females: efficacious contraceptive method during treatment and up to seven days after treatment administration

Exclusion criteria 15

1. 1) Patients already scheduled for long term residential care after acute alcohol inpatient detoxification, not able to maintain the outpatient follow up
2. 2) Patients not willing to attend post-discharge visits whatever the reason
3. 3) Any unstable medical condition at entry, such as delirium, acute hepatic failure, hypokalaemia, liver cirrhosis whatever the stage, acute or chronic severe renal failure or any acute psychiatric condition
4. 4) Liver enzymes (ALT and/or AST) above 3 times the upper limit of normal and/or bilirubin above 2 times the upper limit of normal
5. 5) Current medication or need for medication with treatments metabolized by CYP 2C19 or CYP3A4 or UGT enzymes and having strong inhibitor/inducer properties (see list above), and/or current medication or need for medications containing valproate and derivates
6. 6) Any medical history of epileptic seizure
7. 7) Patients with current or past history of cardiac arrhythmias, myocardial infarction and stroke
8. 8) any history of suicidal attempt in the past 5 years or a score ≥1 to the Suicidal Ideation Attributes Scale (SIDAS)
9. 9) To facilitate efficacy data interpretation, patients currently receiving or wanting to receive another approved pharmacological treatment aimed at alcohol abstinence maintenance (acamprosate, baclofene, disulfiram, nalmefene, naltrexone).
10. 10) Other major current DSM 5 severe substance use disorder (like opiates, cocaine, amphetamines, …..) except for tobacco and cannabis smoking and benzodiazepines use disorders.
11. 11) Pregnancy and breast feeding
12. 12) Known hypersensitivity to the active substance or to any of the excipients (including PEG)
13. 13) Patients under guardianship
14. 14) Patients in exclusion periods of other trials
15. 15) Reversely, cannabis use or cannabis use disorders will not be an exclusion criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of patients in each group with documented continuous abstinence at month 1 after discharge, week 6 of the study. Continuous abstinence will be defined by patients self-report of alcohol abstinence using standardized TLFB (time line follow back) scales TLFB at screening visit and daily from Day 0 to Day 10 and 4 (1 per week) after discharge up to week 6 of the study)
2. Furthermore, this self-declaration will be confirmed by clinical examination at each study visits assessing acute alcohol intoxication signs and 6 ethyl glucuronide (Et-OH) urinary assessments performed at each study visit (2 during the inpatient stay and 4 (1 per week) after discharge up to week 6 of the study).

Secondary endpoints 8

1. symptoms check list (PRISE-M) of possible side effects every day from day 1 to 10, and then at each outpatient study visit (4 (1 per week) after discharge up to week 6 of the study). Thus any side effect related to treatment exposure as well as treatment cessation (such as anxiety rebound or withdrawal symptoms related to CBD or increase in cannabis use) could be documented
2. - in case of relapse: drinking days and drinks per day (self-declared using standardized TLFB time line follow back scale over the past week) at the screening visit and daily from Day 0 to Day 10 and 4 (1 per week) after discharge up to week 6 of the study)
3. - alcohol withdrawal scales and craving scales (CIWA-R, , LIKERT craving scale and an adapt version of the OCDS) at the screening visit and every day from day 0 to 10 then at each study visit: 4 (1 per week) after discharge up to week 6 of the study
4. - state anxiety scale (STAI-6 the short form of the Spielberger inventory, composed of 6 Likert scales) at the screening visit and every day from day 0 to 10 then at each study visit: 4 (1 per week) after discharge up to week 6 of the study
5. - Pittsburgh Sleep Quality Index (PSQI) at the screening visit and the last visit. A modified daily version every day from day 0 to 10 then at each study visit a modified weekly version: 4 (1 per week) after discharge up to week 6 of the study
6. - in the subgroup of patients recruited in AP-HP hospitals, plasmatic level of CBD will be determined twice: at D5 and D10. Analysis of cannabinoids in human biological specimens of plasma will rely on an extraction process and a chromatographic separation in LCMSHR (Liquid chromatography coupled to high resolution mass spectrometry) for quantification of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-OH THC and THC-COOH according to guidelines set forth by COFRAC.
7. - self-declared current use of all other substances including tobacco products and nicotine replacement therapies, cannabis, and other substances using standardized TLFB (time line follow back) scales ) at the screening visit and every day from day 0 to 10 then at each study visit: 4 (1 per week) after discharge up to week 6 of the study
8. - in the subgroup of patients who declare themselves as current cannabis users at entry, urinary quantitative determination of cannabinoids by an extraction process and a chromatographic separation in LCMSHR

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

1 Avenue Claude Vellefaux

City

Paris

Postcode

75010

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Florence VORPSAN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Florence VORPSAN

Locations

1 EU/EEA country · 10 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 12 files

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

Application history

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