Cannabis for Chronic Headaches in Adolescents: the CAN-CHA Trial

Study Overview
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Brief Summary
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Chronic headaches are a major cause of disability among adolescents. Cannabis products have supported the management of headaches in adults and may play a role in pediatric chronic pain. We propose a multisite, open-label, tolerability study conducted across three centers in Canada of Cannabidiol-enriched Cannabis Herbal Extract in adolescents (ages 14 to 17 years old) with chronic headaches. The study includes a one month baseline assessment, four months of escalating treatment doses and a weaning period. Our primary outcome is tolerability defined as the number and severity of reported adverse events.

Official Title
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A Multi-Centre, Tolerability Study of a Cannabidiol-enriched Cannabis Herbal Extract for Chronic Headaches in Adolescents: the CAN-CHA Trial

Conditions
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Chronic Migraine

Intervention / Treatment
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* Drug: MPL-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible to participate in this study, an individual must meet all of the following criteria: Adolescents between 14-17 years of age at the time of screening Diagnosed with chronic migraine for more than three months Failed other treatment options on the grounds of safety (tolerability) or efficacy, including but not limited to antidepressants (tricyclic antidepressant or selective norepinephrine reuptake inhibitor), gabapentinoids or topiramate. Females who have reached menarche should have a negative serum pregnancy test during screening. Must be willing to engage with psychology and physiotherapy throughout the trial Exclusion Criteria: As per the investigator judgement, the participant is not an ideal candidate due to a personal issue or medical condition that is likely to impede in the successful completion of the study Participants with a history of post-concussion headache or new daily persistent headache Participants with a diagnosis of medication overuse headache Participants with cardiac, renal or hepatic disease (assessed by the site investigator) Participants with complex regional pain syndrome-II Participants with abnormal ECG findings at baseline (as determined by the investigator) Participants who are on the following medications: opioids, antipsychotics, antimanic, barbiturates, benzodiazepines, muscle relaxants, sedatives, or tramadol. Participants with developmental delay or impairments including autism, cerebral palsy or intellectual disability. Participants with a personal or family history of schizophrenia or psychotic disorders Participants who are pregnant or breast/chest-feeding or plans to become pregnant within the study period or within three months of interventional product discontinuation Participants who cannot commit to using contraception and refraining from recreational cannabis use and driving throughout the study period

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label tolerability trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol-enriched Cannabis Herbal Extract<br>CBD50 plus | Drug: MPL-001<br>* CBD50 plus is a medical cannabis oil with flavouring agent produced under Good Manufacturing Practice by MediPharm Labs and purchased for this study. Each ml of oil contains 2 mg/ml of delta-9-THC and 50 mg/ml of CBD. Participants will receive escalating doses from 0.2-0.4 mg/kg/day of CBD to 0.8-1 mg/kg of CBD per day for four months, with dose increases monthly in 0.2mg/kg increments. Participants will following a weekly weaning protocol.<br>* Other names: medical cannabis oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cannabis-related adverse events | The frequency of adverse events will be measured and characterized using standard CTCAE coding | Reported daily through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency and duration of headache compared to baseline | Reported headache frequency and duration daily and reported as a monthly average documented at baseline. | Reported daily through study completion, an average of 6 months | 
| Pain intensity compared to baseline | The average intensity measured using a Numeric Rating Scale (NRS) will be reported as a percentage change from the monthly average documented at baseline and an increasing score(highest score =10) indicates a greater severity of pain. | Reported daily through study completion, an average of 6 months | 
| Pain impact on participants quality of life compared to baseline | The impact of pain on participants quality of life using the PROMIS Pediatric Pain Interference- Short Form 8a will be reported as a percentage change from the monthly average documented at baseline. | Reported monthly for 6 months | 
| Number of hours of sleep per night compared to baseline | The number of hours of sleep per night will be measured using a actigraphy device | Reported daily through study completion, an average of 6 months | 
| Change in sleep quality | Patient Reported Outcome Measurement Information System (PROMIS) Pediatric Short Form v 2.0 - Pediatric Sleep-Related Impairment 8a scale as a percentage change from the monthly average documented at baseline where a higher number indicates a more sleep related impairment | Reported monthly for 6 months | 
| Change in mood, depression from baseline | PROMIS Pediatric Short Form v2.0 - Depressive Symptoms 8a scale as a percentage change from the monthly average documented at baseline | Reported monthly for 6 months | 
| Change in mood, positive affect from baseline | Change in mood, positive affect will be evaluated using PROMIS Pediatric Positive Affect - Short Form 8 and reported as a percentage change from the monthly average documented at baseline | Reported monthly for 6 months | 
| Change in self-directed goal attainment from baseline | Participants will self-directed goal attainment (participant and parent reported) as a percentage of goal attained at each study visit | Reported monthly for 6 months | 
| Changes in anxiety compared to baseline | Changes in anxiety will be measured using the PROMIS Pediatric Anxiety Short Form v2.0 and reported as percentage change from the monthly average documented at baseline | Reported monthly for 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescents, Children, Cannabis, Migraine, Cannabidiol, Tetrahydrocannbinol