Cannabidiol Extract for Epilepsy

(PTE Trial)

Overseen By Ashley D Zelaski, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dr. Paul Lyons

Must be taking: Anti-epileptic drugs

Must not be taking: Medical marijuana

Disqualifiers: PNES, Pregnancy, Suicidal ideation, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Trial Summary

What is the purpose of this trial?

This prospective double blind phase II study seeks to evaluate the safety and efficacy of BRC-003, a high CBD investigational product, in the treatment of refractory PTE (Post-Traumatic Epilepsy). The research is divided into two phases: an open-label dose-finding phase (Part A) and a subsequent randomized controlled phase (Part B). This design aims to provide a thorough understanding of the investigational product's impact on seizure frequency, seizure severity, mood, anxiety, sleep, and quality of life.

Do I have to stop taking my current medications for this trial?

The trial requires that participants have stable doses of their current anti-epileptic drugs for at least 4 weeks before enrolling, so you do not need to stop taking them. However, you cannot use medical marijuana, cannabis, hemp, or CBD products during the study.

What data supports the effectiveness of the drug BRC-003, High CBD Investigational Product, for epilepsy?

Research shows that CBD-rich extracts, like BRC-003, can help reduce seizures in people with treatment-resistant epilepsy. In studies, about 64% of patients reported fewer seizures, and CBD-rich extracts seemed to work better than purified CBD alone, possibly due to the combined effects of different compounds in the extract. ^{1 2 3 4 5}

Is cannabidiol extract safe for humans?

Studies on cannabidiol (CBD) for epilepsy, including Epidiolex, show it generally has an adequate safety profile, though some drug interactions may occur. These studies involved both children and adults with treatment-resistant epilepsy, and they found that CBD was well-tolerated over long-term use. ^{1 2 6 7 8}

How is the drug BRC-003 different from other epilepsy treatments?

BRC-003, a high CBD investigational product, may offer a unique advantage over purified CBD products due to the potential synergistic effects of CBD with other compounds in the extract, known as the 'entourage effect'. This could result in better seizure control and fewer side effects compared to treatments using only purified CBD. ^{1 4 5 9 10}

Research Team

Paul D Lyons, MD. PhD

Principal Investigator

Valley Health System

Eligibility Criteria

This trial is for adults over 18 with Post-Traumatic Epilepsy who haven't had success controlling seizures after trying at least two anti-epileptic drugs (AEDs) or equivalent treatments. They should be on a stable dose of 1-4 AEDs, and if using devices like VNS, DBS, or RNS, settings must be stable for 3 months. Those on a ketogenic diet need to have been on a consistent ratio for the same duration.

Inclusion Criteria

Participants must meet all of the following criteria to be eligible for enrollment into the study:

I have been on 1-4 stable epilepsy medications for at least 4 weeks.

I have been diagnosed with pulmonary thromboembolism.

Exclusion Criteria

Inability or failure to comply with study visits, requirements and/or instructions

For Part B, prior enrollment in Part A of the study

I have used cannabis or CBD products in the last 30 days or plan to during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Dose-finding (Part A)

Participants receive BRC-003 to determine the optimal dose

12 weeks

Regular visits for dose adjustment and monitoring

Randomized Controlled Phase (Part B)

Participants are randomized to receive either BRC-003 or placebo

12 weeks

Regular visits for efficacy and safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BRC-003

Trial Overview The study tests BRC-003, a high CBD cannabis extract against placebo in reducing seizure frequency and severity in refractory PTE patients. It includes an initial open-label phase to find the right dose followed by a randomized controlled phase where participants are blindly assigned to receive either BRC-003 or placebo.

Participant Groups

Group I: Part A and Part B Experimental Treatment 1 Intervention

Interventions: Drug: BRC-003 (High Cannabidiol Botanical Extract) 100 mg/mL

Group II: Part B Placebo Group 1 Intervention

Placebo Comparator: 1 Placebo Half of the patients will receive PO placebo Interventions: Drug: Placebo

BRC-003 is already approved in United States, European Union 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 Epidyolex for:

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

Who Is Running the Clinical Trial?

Dr. Paul Lyons

Lead Sponsor

Trials

1

Recruited

50+

Biopharmaceutical Research Company

Collaborator

Trials

3

Recruited

100+

Findings from Research

In a study involving 169 participants with treatment-resistant epilepsy, highly purified cannabidiol (CBD) demonstrated significant reductions in seizure frequency and severity over a two-year period, with 61% of children and 71% of adults achieving at least a 50% reduction in seizures by the end of the study.

CBD was generally well tolerated, with the most common side effects being diarrhea, sedation, and decreased appetite, and only a minority of participants discontinued treatment due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of highly purified cannabidiol for treatment refractory epilepsy. Gaston, TE., Ampah, SB., Martina Bebin, E., et al.[2021]

In a study of 42 patients with epilepsy, cannabidiol (CBD) was found to be an effective treatment, with 29% of participants achieving a significant reduction in seizure frequency of 80% or more after 12 months.

The treatment was generally safe, with 52.3% of patients experiencing adverse events, primarily drowsiness and diarrhea, but the retention rate for CBD treatment remained high at 71.4% after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with cannabidiol as add-on treatment in drug-resistant epilepsy. Vicino, W., Muccioli, L., Pondrelli, F., et al.[2023]

In a study involving 8 adults with refractory epilepsy, taking purified oral cannabidiol (CBD) capsules with food significantly increased the maximum concentration (Cmax) of CBD in the blood by 14 times and the overall drug exposure (AUC0-∞) by 4 times compared to fasting conditions.

No adverse events were reported during the study, indicating that CBD capsules are safe for use in this population, and the findings suggest that the fat content in meals can greatly enhance the bioavailability of CBD, which is important for optimizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy. Birnbaum, AK., Karanam, A., Marino, SE., et al.[2020]

In a study of 47 patients with refractory epilepsy, highly purified cannabidiol (CBD) was found to be effective in reducing seizure frequency, regardless of whether it was used with clobazam (CLB) or not.

Patients taking CBD alongside CLB had a significantly higher responder rate (more than 50% reduction in seizures) at the point of best seizure control within the first year, indicating that combining these treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Savage, TE., Sourbron, J., Bruno, PL., et al.[2021]

In a meta-analysis of 11 observational studies involving 670 patients with refractory epilepsy, approximately 64% reported a reduction in seizure frequency when treated with cannabidiol (CBD)-based products, with CBD-rich extracts showing a higher improvement rate (71%) compared to purified CBD (46%).

Patients using CBD-rich extracts experienced fewer adverse effects and required lower average doses (6.0 mg/kg/day) than those using purified CBD (25.3 mg/kg/day), suggesting that CBD-rich extracts may offer a better therapeutic profile, potentially due to the 'Entourage effect' from other compounds in the extracts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. Pamplona, FA., da Silva, LR., Coan, AC.[2020]

Cannabidiol (CBD), particularly in the form of Epidiolex®, has shown efficacy and an adequate safety profile in treating treatment-resistant epilepsy (TRE) in children and young adults, especially those with Dravet Syndrome and Lennox-Gastaut Syndrome, based on Phase 3 randomized controlled trials.

Despite the historical use of cannabis for epilepsy, valid data on the safety and efficacy of artisanal cannabis preparations remains lacking, highlighting the importance of relying on well-conducted clinical trials for treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids in treatment-resistant epilepsy: A review. O'Connell, BK., Gloss, D., Devinsky, O.[2022]

In a study of 139 participants with treatment-resistant epilepsy, the use of highly purified cannabidiol (CBD; Epidiolex®) led to significant reductions in adverse events, seizure severity, and seizure frequency over 12 weeks, with improvements sustained for up to 48 weeks.

The study demonstrated that CBD was well-tolerated, with a decrease in adverse events from 40.8 to 33.2 and a reduction in seizure severity scores from 80.7 to 39.2, indicating its efficacy as a treatment option for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. Szaflarski, JP., Bebin, EM., Cutter, G., et al.[2019]

Epidiolex, a 99% pure oral CBD extract, has been shown to significantly reduce seizure frequency in patients with medically refractory epilepsy, leading to its FDA approval.

The review highlights the safety profile of Epidiolex, noting that while it is effective, understanding its adverse effects is crucial for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. Sekar, K., Pack, A.[2020]

Cannabidiol (CBD) has been approved for use as an adjunctive therapy for treating epileptic seizures in patients aged 2 years and older with Lennox-Gastaut syndrome and Dravet syndrome, showing its efficacy in reducing seizures when combined with clobazam.

Experts recommend a gradual dose escalation of CBD over 4 weeks to optimize treatment, and advise monitoring for adverse effects, suggesting that treatment should continue for at least 6 months if well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for the treatment of Lennox-Gastaut syndrome and Dravet syndrome: experts' recommendations for its use in clinical practice in Spain. García-Peñas, JJ., Gil Nagel-Rein, A., Sánchez-Carpintero, R., et al.[2022]

Epidiolex™, a purified form of cannabidiol (CBD), shows promise in controlling seizures in Dravet syndrome, with its mechanism linked to the mitochondrial glycine cleavage system, specifically the GcvH1 protein.

CBD appears to regulate methionine levels by inhibiting its synthesis, which is altered in Dravet syndrome and associated with seizure activity, suggesting a novel metabolic pathway involved in its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. Perry, CJ., Finch, P., Müller-Taubenberger, A., et al.[2021]

References

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

Long-term safety and efficacy of highly purified cannabidiol for treatment refractory epilepsy. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Real-world experience with cannabidiol as add-on treatment in drug-resistant epilepsy. [2023]

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

Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. [2020]

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

Cannabinoids in treatment-resistant epilepsy: A review. [2022]

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

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. [2020]

9. Spain pubmed.ncbi.nlm.nih.gov

Cannabidiol for the treatment of Lennox-Gastaut syndrome and Dravet syndrome: experts' recommendations for its use in clinical practice in Spain. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. [2021]