A trial to investigate the effects of Cannabidiol plus Naltrexone on alcohol craving in patients with alcohol dependence

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zentralinstitut Fuer Seelische Gesundheit

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

16 Jun 2025 → ongoing

Decision date (initial)

2025-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BMBF

External identifiers

EU CT number

2024-518164-12-00

ClinicalTrials.gov

NCT06845124

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the effect of either 800mg or 1200mg oral CBD in addition to background treatment with 50mg oral Naltrexone on the reduction of alcohol craving compared to the effects of a placebo in addition to standard treatment with 50mg oral Naltrexone.

Secondary objectives 10

1. Investigation of the effects of either 800mg or 1200mg CBD in addition to background treatment with 50mg oral Naltrexone versus Placebo plus 50mg Naltrexone on: i) changes in alcohol craving
2. changes in quality of life
3. changes in depressive symptoms
4. changes in state and trait anxiety
5. Patient reported outcomes (i.e., subjective burden and benefit of treatment and subjective effects on alcohol craving, perceived stress, mood, anxiety, well-being, daily functioning, and confidence in abstinence)
6. CBD plasma levels to detect effects of active intervention on CBD blood plasma levels; (only for patients at CIMH site)
7. time to relapse to alcohol, cumulative alcohol use and percent heavy drinking days
8. average weekly alcohol consumption and maximum weekly craving assessed weekly via smartphone-based e-diary during the follow-up (optional, only for patients that agree to use the study-specific app)
9. Safety determined by the assessment of adverse events and serious adverse events
10. Changes in neural brain activation assessed by the blood oxygenated level dependent (BOLD) response, during presentation of alcohol cues, natural reward cues, presentation of emotional faces and neutral shapes, during inhibition of motor responses and functional connectivity during resting state (only for patients at CIMH site).

Conditions and MedDRA coding

Alcohol dependence

Study design 3 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

After publication of the primary objective, the data might be provided to interested scientists on request (e.g. for meta-analyses, health related registers or other scientific questions). Individual participant data (IPDs) will be made available, as far as legally possible. IPDs (including metadata such as data dictionaries) that underlie results concerning primary or secondary endpoints reported in a published scientific article will be shared on demand after deidentification. Furthermore, the following documents may be made available: Study Protocol, Statistical Analysis Plan or Informed Consent Form.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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

Exclusion criteria 9

1. Current psychotic or bipolar disorder or current severe depressive episode with suicidal ideations
2. 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)
3. Positive drug screening (amphetamines/ecstasy, opiates, cocaine, barbiturates)
4. Pregnancy, lactation or breastfeeding
5. Current severe somatic comorbidities: severe liver cirrhosis [stage: CHILD B or C]. epilepsy determined by medical history or prolonged or shortened QT intervals [determined by ECG]
6. Patients with elevated transaminase levels (GOT or GPT) above three times the upper limit normal (ULN) value with elevated bilirubin levels above twice the ULN value
7. 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
8. Participation in other clinical trials or observation period of competing clinical trials, respectively.
9. Acute suicidal tendency or acute endangerment of self and others

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference of alcohol craving (Obsessive Compulsive Drinking Scale, OCDS-G) between baseline (visit 2, day -2) and end of treatment (visit 5, day 14)

Secondary endpoints 10

1. difference from baseline (visit 2, day -2) of OCDS-G craving scores to visits 4 (day 7), 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196);
2. difference from baseline of Quality of life (WHO-QOL-BREF scores) to visits 5 (day 14), 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196);
3. difference from baseline of depressive symptoms (BDI-II scores) to visit 5 (day 14).
4. difference from baseline of state and trait anxiety (STAI scores) to visit 5 (day 14).
5. patient reported outcomes (set of items) at visit 3 (day 1), 4 (day 7), 5 (day 14), 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196));
6. CBD plasma levels [visit 3 (day1) and 5 (day14)] (only for patients at CIMH site)
7. time to relapse, cumulative alcohol use and percent heavy drinking days [visit 5 (day 14), 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196)]
8. Average weekly alcohol consumption and maximum weekly craving assessed every 7th day during the follow up period, starting after visit 5 (day 14) and continuing until visit 9 (day 196) (optional, only for patients that agree to use the study-specific app)
9. differences of neural brain activation during presentation of alcohol cues, natural reward cues, presentation of emotional faces and neutral shapes, during inhibition of motor responses and during resting state from baseline (visit 2, day -2) to visit 5 (day 14) (only for patients at CIMH site)
10. differences of alcohol craving (visual analogue scale), response times, rates of errors, rates of correct responses and omission rates during the fMRI paradigms from baseline (visit 2, day -2) to visit 5 (day 14) (only for patients at CIMH site)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zentralinstitut Fuer Seelische Gesundheit

Sponsor organisation

Zentralinstitut Fuer Seelische Gesundheit

Address

Luisenring J 5

City

Mannheim

Postcode

68159

Country

Germany

Scientific contact point

Organisation

Zentralinstitut Fuer Seelische Gesundheit

Contact name

Prof. Dr. Dr. Patrick Bach

Public contact point

Organisation

Zentralinstitut Fuer Seelische Gesundheit

Contact name

Prof. Dr. Dr. Patrick Bach

Third parties 3

Locations

1 EU/EEA country · 2 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 13 files

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

Application history

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