Cannabidiol as add-on Therapy for Children With Refractory Epilepsy (CBD-uN1que), a High-quality Individualized Approach: a Series of N-of-1 Trials

NCT07668856 | Recruiting Phase 3

• 1 other identifier: 2023-507843-12-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if cannabidiol ("CBD-oil") works to treat severe epilepsy in children. It will also learn about the safety of cannabidiol. The main questions it aims to answer are:

• Does cannabidiol lower the number of seizure in children with severe epilepsy?
• Does cannabidiol effect other outcomes such as behaviour, sleep, communication, activities?
• What medical problems do participants have when taking cannabidiol? Researchers will compare cannabidiol to a placebo (a look-alike oil that contains no cannabidiol) to see if drug cannabidiol works to treat severe epilepsy. All participants will receive both the cannabidiol and the placebo during different periods. At the end of the trial, we will evaluate for each patient seperately, whether seizures were less or more frequent during cannabidiol periods or placebo periods, to see what works best for every patient seperately. Participants will:
• Register their seizures in a digital application during 4 to 6 periods. During these periods, CBD oil of placebo will be provided
• Take CBD oil during 2 to 3 periods. One period will last around 7 weeks.
• Also take placebo oil during the other 2 to 3 periods
• Have a blood test every 7 weeks to monitor for safety and possible adverse effects
• Visit the clinic once every 15 weeks for checkups and tests
• Fill in questionnaires about quality of life, functioning, sleep, behaviour, epilepsy severity every 7 weeks.

Conditions

Refractory Epilepsy in Children; Refractory Epilepsy; Epilepsy

Keywords

Refractory epilepsy; rare diseases; Cannabidiol.; bedrolite; n-of-1 trial; medicinal cannabis

Outcome Measures

Primary Outcomes (1)

• Seizure frequency

  The primary outcome measure is the change from baseline in daily seizure frequency during active treatment periods and placebo periods, at the individual level and the aggregated group level. This will be collected by the participants' caregivers using an electronic diary (app) developed specifically for epilepsy research, to register seizure frequency and -type, and the need for emergency medication, for up to 7 days in hindsight.

  Daily, from start of baseline after enrollment to the end of the last treatment cycle (each cycle - consisting of two periods with run in, taper and washout phases - is 15 weeks). Adittionally, untill up to 6 months during open label extension phase.

Secondary Outcomes (10)

• Seizure free days

  Registered daily using a seizure diary. Analysis endpoints specifically after completion of cycle 2 and (if applicable) cycle 3 and after 6 months of open label extension (if applicable), or else at withdrawal. Each cycle (two periods) lasts 15 weeks.

• Response rates

  Seizures will be registered daily using a seizure diary. Analysis endpoints after cycle 2 and (if applicable) cycle 3 and after 6 months of open label extension (if applicable), or else at withdrawal. Each cycle (two periods) lasts 15 weeks.

• Patient-centered outcome measures: QOLCE-55

  - Once durine the 4-week baseline - Once every period (up to maximum of 6 periods), one period lasts 7 weeks. - At the and of the open label extension phase after 6 months (if applicable).

• Patient-centered outcome measures: GASE scale

  Once durine the 4-week baseline - Once every period (up to maximum of 6 periods), one period lasts 7 weeks. - At the and of the open label extension phase after 6 months (if applicable).

• Patient-centered outcome measures: GCI scale

  - Once durine the 4-week baseline. - Once every period (up to maximum of 6 periods), one period lasts 7 weeks. - At the and of the open label extension phase after 6 months (if applicable).

Other Outcomes (3)

• Productivity Cost Questionnaire iPCQ

  - Once durine the 4-week baseline. - Once every period (up to maximum of 6 periods), one period lasts 7 weeks. - At the and of the open label extension phase after 6 months (if applicable).

• Medical Consumption Questionnaire iMCQ

  - Once durine the 4-week baseline. - Once every period (up to maximum of 6 periods), one period lasts 7 weeks. - At the and of the open label extension phase after 6 months (if applicable).

• Quality of life: EQ-5D-Y questionnaire

  - Once durine the 4-week baseline. - Once every period (up to maximum of 6 periods), one period lasts 7 weeks. - At the and of the open label extension phase after 6 months (if applicable).

Study Arms (2)

Active treatment with CBD oil

ACTIVE COMPARATOR

All participants will undergo one to three treatment cycles. In each cycle, each participant will receive both the active comparator as the placebo comparator. The investigational medicinal product (IMP): Bedrolite, which is a full spectrum extract of Cannabis sativa L. "Rensina", with a CBD:THC ratio of approximately 26:1. Cannabidiol will be titrated up to a dosage of 2.5-20mg/kg/day, which is in line with previous clinical trials. There is scarce evidence in literature on optimal dosing of this specific CBD:THC preparation, therefore, directly after the baseline period, a titration phase is used to determine the maximum tolerated dose. The maximum daily dose is set at 1000mg CBD per day. Therefore, for patients weighing over 50 kg, a calculation weight of 50 kg will be used.

Drug: Cannabidiol (CBD) oral solution

Placebo

PLACEBO COMPARATOR

Placebo is identical to the IMP apart from the active ingredients (less than 0.5% CBD/0.02%THC ), with identical packaging.

Other: Placebo

Interventions

Cannabidiol (CBD) oral solution DRUG

Bedrolite, which is a full spectrum cannabis extract with 10%CBD/0.4%THC. Cannabidiol will be titrated up to a dosage of 2.5-20mg/kg/day, dosed twice daily.

Active treatment with CBD oil

Placebo OTHER

Cannabis extract with less than 0.5% CBD/0.02%THC

Placebo

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Minimum age of 1 year old and maximum age of 18 years old.
• Confirmed diagnosis of refractory epilepsy according to ILAE criteria
• At least 4 countable seizures (not all in one week) of epileptic origin, during the 4-week baseline period while receiving care as usual.
• All medication doses or other interventions for epilepsy must have been stable for one month prior to screening and the participants/parents and treating physicians are willing to maintain the current treatment regimen throughout the trial.
• Informed consent/ of legal representative/ parents.
• Presence of a consistently available patient caregiver for proxy-reports.

You may not qualify if:

• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (cannabis extract and refined peanut oil, generally safe for patients with peanut allergy)
• History or current signs of significantly impaired liver function, such as bilirubin level ≥ 2 x upper limit of normal, or presence of liver damage as indicated by levels of alanine aminotransferase and/or aspartate aminotransferase ≥ 3 x upper limit.
• Pregnancy, breastfeeding, or intention to become pregnant throughout the trial or within 3 months of completing treatment
• Cardiac disease including: Structural heart disease with hemodynamic significance, heart failure, ischemic heart disease, Brugada syndrome, long-QT syndrome, cardiac arrythmia
• Glaucoma
• Ongoing evaluation for epilepsy surgery
• Unstable medical condition, other than refractory epilepsy, that is of significant influence on participation in the trial; significance to be determined with the treating physician/pediatric neurologist
• History of recreational or medicinal cannabis use, or cannabinoid-based medications, within three months prior to screening and the patient is unwilling to abstain for the duration of the study
• Planned intervention under general anesthesia interfering with the baseline period; or any planned major surgery within the duration of the trial
• Expected inability to undergo blood sampling due to anxiety or resistance
• Use of clobazam dosage of \> 0,5 mg/kg/day in the last month

Sponsors & Collaborators

• UMC Utrecht: lead
• Stichting Epilepsie Instellingen Nederland: collaborator
• Epilepsiecentrum Kempenhaeghe: collaborator
• Erasmus Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Drug Resistant Epilepsy; Epilepsy; Rare Diseases

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Central Study Contacts

Marit van de Wiel, MD

CONTACT

088 755 5555; m.vandewiel@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Pediatric Neurology

Model Details: The CBD-uN1que trial is designed as a series of 50 double-blind randomized placebo-controlled multiple crossover superiority trials. Each n-of-1 trial consists of 1-3 treatment "cycles", each with 2 treatment "periods" in which the participant is randomized to one of the two treatment arms (cannabidiol or placebo in a 1:1 ratio. Before starting the trial, each patient will start with a 4-week baseline period to assess main baseline outcome measures, and a 19-days dose-titration phase to assess an individualized optimal tolerated dosage (titrated to a dosage of 2.5-20mg/kg/day CBD), administered twice daily. Each period consists of a 7-day run-in period to reduce risk of adverse effects, 4-week treatment period (CBD or placebo), a 10-day taper period to reduce withdrawal symptoms and a 7-day washout period with no intervention to reduce carryover effects. If efficacy is shown in the n-of-1 trial , participants can choose to enter an open-label extension phase of 6 months.

Study Record Dates

• First Submitted: March 25, 2026
• First Posted: June 25, 2026
• Study Start: February 6, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 25, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Protocol will be published before last inclusion of last patient. Informed consent, analytical code and individual data will be shared within one year of last visit of last participant.
• Access Criteria: Access will be granted to researchers affiliated with recognized academic or clinical institutions who submit a methodologically sound research proposal. Proposals will be reviewed by the researches involved in our CBD consortium. Approved applicants will be granted access through a secure remote data access environment or controlled data repository.

Locations

NL (1)