Cannabidiol for Chronic Liver Injury Prevention

Recruiting at 27 trial locations

Overseen By Medical Enquiries

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: GW Research Ltd

Must be taking: Epidiolex

Must not be taking: Cannabis, Synthetic cannabinoids

Disqualifiers: Pregnancy, Liver fibrosis, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week initial, then ongoing

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will monitor for potential chronic liver injury and liver fibrosis, in participants treated with cannabidiol oral solution.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not use recreational or medicinal cannabis, or synthetic cannabinoid-based medications other than Epidiolex. Any non-drug therapies, like a ketogenic diet, should be stable before and during the study.

What evidence supports the effectiveness of the drug Cannabidiol (CBD) for preventing chronic liver injury?

Research suggests that CBD may help protect the liver by reducing inflammation and oxidative stress, which are harmful processes that can damage liver cells. Studies in mice have shown that CBD can prevent liver damage caused by alcohol and high-fat diets, indicating its potential to help with liver health. ^{1 2 3 4 5}

Is cannabidiol (CBD) safe for human liver health?

Research shows that CBD can cause liver enzyme elevations in some people, which may indicate liver stress or injury. In healthy adults, some studies found no significant liver issues, while others reported potential liver injury at high doses. People with liver problems may need lower doses and should be cautious. ^{1 2 3 5 6}

How does the drug Cannabidiol (CBD) differ from other treatments for chronic liver injury prevention?

Cannabidiol (CBD) is unique because it is a non-psychoactive component of marijuana that helps prevent liver damage by reducing inflammation and oxidative stress, specifically by inhibiting the NFκB-NLRP3 inflammasome-pyroptosis pathway. Unlike other treatments, CBD has shown potential in managing liver conditions related to alcohol and high-fat diets, and it is being explored for its ability to alleviate liver fibrosis and steatosis. ^{1 2 4 5 7}

Eligibility Criteria

This trial is for individuals with Lennox Gastaut Syndrome, Dravet Syndrome, or Tuberous Sclerosis who are already taking or starting Epidiolex (cannabidiol) therapy. They must avoid heavy exercise before visits and maintain stable non-drug therapies. Exclusions include recent cannabis use, planned major surgery within five years, pregnancy, significant health risks as determined by the investigator, participation in other drug trials within three months prior to screening, certain liver conditions or diseases that cause liver fibrosis.

Inclusion Criteria

I have been on a stable non-drug therapy, like a special diet, for at least 4 weeks.

I am currently taking or will start taking Epidiolex for seizures.

Participant is willing to refrain from strenuous exercise 48 to 72 hours prior to all study visits with the exception of unscheduled visits.

Exclusion Criteria

Participation in any clinical trial involving an investigational medicinal product within 3 months prior to the Screening Visit or at any point during this study.

Following a physical examination, if the participant has any abnormalities that, in the opinion of the investigator, would prevent the participant from safe participation in the study.

I plan to undergo epilepsy or major surgery within the next five years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cannabidiol oral solution starting at 5 mg/kg/day for 1 week, then increasing to 10 mg/kg/day

1 week initial, then ongoing

Monitoring

Participants are monitored for potential chronic liver injury and liver fibrosis

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cannabidiol

Trial Overview The study is monitoring participants treated with cannabidiol oral solution for chronic liver injury and liver fibrosis. Cannabidiol is being tested for its long-term safety on the liver among those using it to manage seizures related to specific syndromes.

Participant Groups

Group I: Cannabidiol Experimental Treatment 1 Intervention

Cannabidiol solution 100 milligrams per milliliter (mg/mL) will be administered orally at a dose level of 5 mg/kg/day for 1 week, then increase to 10 mg/kg/day by the participant or their caregiver twice each day (morning and evening).

Cannabidiol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

GW Research Ltd

Lead Sponsor

Trials

36

Recruited

3,200+

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Jazz Pharmaceuticals Research UK Limited

Industry Sponsor

Trials

1

Recruited

150+

Findings from Research

A study involving 30 subjects with varying degrees of hepatic impairment showed that a single 200-mg dose of cannabidiol (CBD) was rapidly absorbed, with the time to maximum plasma concentration ranging from 2 to 2.8 hours across all groups.

Significantly increased exposure to CBD was observed in subjects with moderate (2.45 times) and severe (5.15 times) hepatic impairment compared to those with normal liver function, indicating that dose adjustments are necessary for these patients, while CBD was well tolerated with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment. Taylor, L., Crockett, J., Tayo, B., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

A Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

CBD Alleviates Liver Injuries in Alcoholics With High-Fat High-Cholesterol Diet Through Regulating NLRP3 Inflammasome-Pyroptosis Pathway. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Observed Impact of Long-Term Consumption of Oral Cannabidiol on Liver Function in Healthy Adults. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results of a Phase I Clinical Trial. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol markedly alleviates skin and liver fibrosis. [2022]