Epidiolex for Anxiety in Pediatric Epilepsy

Overseen By Catherine Eliades

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Must be taking: Anticonvulsants

Must not be taking: Benzodiazepines

Disqualifiers: Psychotic illness, Substance abuse, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective open label study assessing the efficacy and tolerability of pharmaceutical grade cannabidiol--Epidiolex (R), for the treatment of anxiety in pediatric patients with pediatric epilepsy that has been difficult to treat and requires ongoing use of anticonvulsant medication.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current anticonvulsant medications, as ongoing use is necessary. However, you must not use any CBD products for 14 days before the study and during the study. If you are taking benzodiazepines regularly, you may need to stop, except for emergency use.

What data supports the effectiveness of the drug Epidiolex for anxiety in pediatric epilepsy?

Epidiolex, a form of cannabidiol (CBD), has been shown to reduce seizures in conditions like Dravet syndrome and Lennox-Gastaut syndrome, which are types of epilepsy. While these studies focus on seizure reduction, they suggest that Epidiolex can have a positive impact on epilepsy-related symptoms, which might include anxiety. ^{1 2 3 4 5}

Is Epidiolex (CBD) safe for use in children with epilepsy?

Epidiolex (CBD) has been studied for safety in children with epilepsy, showing common side effects like sleepiness and diarrhea. Some studies noted interactions with other medications, leading to increased side effects, but adjusting the dose slowly can improve safety. Overall, it is generally considered safe, but monitoring for side effects is important. ^{1 3 4 5 6}

How is the drug Epidiolex unique for treating anxiety in pediatric epilepsy?

Epidiolex is unique because it is a plant-derived cannabidiol (CBD) specifically approved for certain types of epilepsy, like Lennox-Gastaut and Dravet syndromes, and is now being explored for anxiety in pediatric epilepsy. Unlike other treatments, it is a highly purified form of CBD, which may offer a different mechanism of action compared to traditional anti-seizure medications. ^{1 2 4 5 7}

Research Team

Jay Salpekar

Principal Investigator

Principal Investigator

Eligibility Criteria

This trial is for children and teens aged 6-18 with epilepsy and anxiety who are on anticonvulsant medication, haven't had severe seizures recently, can take oral medicine, and aren't using other CBD products. Participants need reliable caregivers for consent and must use birth control if sexually active.

Inclusion Criteria

Participants who are sexually active must agree to sexual abstinence or to use an approved birth control method for the full duration of study participation

I experience anxiety that affects my daily activities.

I have epilepsy and need medication to control my seizures.

Exclusion Criteria

Pregnant, planning to become pregnant, breastfeeding, or failing to use an appropriate method of contraception

My caregiver or legal guardian cannot fully understand or consent to the study procedures for me.

I am taking epilepsy drugs, but I'm open to extra monitoring if needed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active treatment with flexible dose titration of Epidiolex®

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Epidiolex

Trial Overview The study tests Epidiolex (cannabidiol) to see if it helps with anxiety in young patients with hard-to-treat epilepsy. It's an open label study where everyone knows they're getting the actual drug, not a placebo.

Participant Groups

Group I: treatment arm Experimental Treatment 1 Intervention

open label treatment intervention

Epidiolex 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

Who Is Running the Clinical Trial?

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Lead Sponsor

Trials

93

Recruited

25,200+

Findings from Research

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]

Pure, plant-derived cannabidiol (CBD; Epidiolex) has been shown to significantly reduce seizure frequencies in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) by 17% to 23% compared to placebo, making it an effective adjunctive therapy for treatment-resistant epilepsy.

CBD is generally well tolerated, with common side effects including somnolence, diarrhea, and elevated liver enzymes, and it is the first cannabis-derived medication approved by the FDA for these conditions, providing a new treatment option for patients aged 2 years and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. Chen, JW., Borgelt, LM., Blackmer, AB.[2020]

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 108 patients with refractory epilepsy taking Epidiolex®, 75% remained on the treatment at the final evaluation, indicating that it is generally well-tolerated and effective for long-term use.

However, 46.3% of patients experienced treatment-emergent adverse effects, with 14.5% discontinuing due to these effects, highlighting the need for further research on managing side effects and drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy. Georgieva, D., Langley, J., Hartkopf, K., et al.[2023]

Epidiolex® (CBD) is effective for treating epilepsy in patients over 2 years old, but it can interact with other medications, as seen in a case where it contributed to lithium toxicity in a patient with Lennox-Gastaut syndrome.

After discontinuing lithium due to toxicity, the patient improved and remained seizure-free on CBD and two other antiseizure medications, highlighting the importance of monitoring drug interactions when adding CBD to treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Drug Interactions Between Cannabidiol and Lithium. Singh, RK., Dillon, B., Tatum, DA., et al.[2020]

In a study involving 125 pediatric patients with rare epilepsies, a slower titration protocol for cannabidiol (CBD) resulted in better tolerance and a significant reduction in seizure frequency, with 37.8% of patients experiencing at least a 50% reduction in seizures after 6 months.

While adverse events (AEs) were reported in nearly half of the patients, mainly including somnolence and asthenia, the overall efficacy of CBD was comparable to previous studies, suggesting that a gradual increase in dosage may enhance patient safety without compromising therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study. D'Onofrio, G., Kuchenbuch, M., Hachon-Le Camus, C., et al.[2020]

Epidiolex® (cannabidiol) is an FDA-approved medication for treating epilepsy associated with Lennox-Gastaut and Dravet syndromes, showing promise for treatment-resistant epilepsy.

A case study of a 23-year-old female revealed a delayed skin rash related to Epidiolex®, highlighting the need to monitor for potential side effects even when they are rare in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidiolex-induced skin rash. Singh, J., Antimisiaris, MF.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. [2020]

3. 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]

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

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy. [2023]

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

Drug-Drug Interactions Between Cannabidiol and Lithium. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study. [2020]

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

Epidiolex-induced skin rash. [2021]