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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BRC-003, a high-CBD (cannabidiol) extract, to determine its effectiveness for people with difficult-to-treat seizure conditions known as Post-Traumatic Epilepsy (PTE). Researchers aim to find out if BRC-003 can reduce seizure frequency and severity, and improve mood, anxiety, sleep, and overall quality of life. The trial consists of two parts: first, determining the right dose, then comparing the treatment with a placebo (a pill with no active ingredient). Individuals who have tried at least two anti-seizure medications without success and have stable medication doses might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that BRC-003 is likely to be safe for humans?

Research has shown that cannabidiol (CBD) extracts, such as BRC-003, may help treat epilepsy. In earlier studies, CBD-rich extracts were generally well-tolerated by people with epilepsy, though some experienced side effects like tiredness, diarrhea, and changes in appetite.

A review of studies found that using CBD can increase the risk of some unwanted effects. It's important to remember that reactions vary, and not everyone will experience these side effects.

This study is in Phase 2, indicating that BRC-003 has already passed initial safety tests. This phase will provide more information about its safety and effectiveness for people with post-traumatic epilepsy. Prospective participants should consult their doctor to determine if joining the trial aligns with their health needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for epilepsy, which often include medications like valproate or lamotrigine, BRC-003 is a high cannabidiol botanical extract. Cannabidiol, derived from cannabis plants, offers a unique approach by potentially reducing seizures through its interaction with the endocannabinoid system, a different mechanism than most traditional antiepileptic drugs. Researchers are excited about BRC-003 because it could provide an alternative for patients who don't respond well to existing medications, with possibly fewer side effects.

What evidence suggests that BRC-003 might be an effective treatment for epilepsy?

Research has shown that CBD (cannabidiol) can help reduce seizures in people with epilepsy. One study found that patients using CBD experienced an average reduction of 43.9% in monthly drop seizures. In the current trial, BRC-003, a high CBD extract, is being studied for its potential to decrease the number and severity of seizures in people with hard-to-treat post-traumatic epilepsy (PTE). Hard-to-treat epilepsy refers to seizures that persist despite other treatments. Based on these findings, researchers are studying BRC-003 for its potential to improve life for those facing this challenging condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Paul D Lyons, MD. PhD

Principal Investigator

Valley Health System

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06523725?term=AREA%5BConditionSearch%5D(%22Epilepsy,%20Post-Traumatic%22)&rank=6

Trial Investigating the Safety and Efficacy of BRC-003 in ... 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 ...

2. withpower.com withpower.com/trial/phase-2-epilepsy-post-traumatic-7-2024-7089a

Cannabidiol Extract for Epilepsy (PTE Trial) 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 ...

3. clinicaltrial.be clinicaltrial.be/en/details/459292?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Trial Investigating the Safety and Efficacy of BRC-003 in... Approximately 30 to 50% of patients with PTE may develop refractory epilepsy, wherein seizures persist despite treatment with multiple ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7604476/

Cannabidiol in the Treatment of Epilepsy: A Focused Review ... The results confirmed the efficacy of CBD with a median percentage reduction in monthly drop seizure frequency from a baseline of 43.9% in patients treated with ...

5. ctv.veeva.com ctv.veeva.com/study/trial-investigating-the-safety-and-efficacy-of-brc-003-in-refractory-post-traumatic-epilepsy

Trial Investigating the Safety and Efficacy of BRC-003 in ... Approximately 30 to 50% of patients with PTE may develop refractory epilepsy, wherein seizures persist despite treatment with multiple ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6143706/

Potential Clinical Benefits of CBD-Rich Cannabis Extracts ... CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy.

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2803957

Adverse Events of Cannabidiol Use in Patients With Epilepsy In this systematic review and meta-analysis of clinical trials, the use of CBD to treat patients with epilepsy was associated with an increased risk of several ...