Bringing Relief to Adolescents Naturally Using Melatonin for Migraine

Study Overview
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Brief Summary
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Migraine in adolescents is common and effective and safe preventive treatments are needed. This is a pilot randomized controlled trial of melatonin versus placebo for migraine prevention in adolescents 12-17 years old.

Detailed Description
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This is a pilot randomized controlled trial of melatonin vs. placebo for migraine prevention in adolescents 12-17 years old. The main goal of this pilot study is to estimate variance in the outcome measures to help with planning the future fully powered study. Participants will have an in person enrollment visit, followed by phone follow up visits and headache diary data collection via smart phone or internet.

Official Title
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Melatonin for Migraine Prevention in Adolescents: A Pilot Remote Trial: The BRAiN-M Study

Conditions
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Migraine in Adolescents

Intervention / Treatment
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* Drug: Melatonin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12-17 years and weight ≥40 kg, to allow consistent dosing for all participants of the melatonin dose that has been found to be effective in adults Resides in California Headache fulfills International Classification for Headache Disorders, Third Edition (beta version)33 criteria for episodic migraine (with or without aura) in adolescents Has been experiencing episodic headaches for at least six months Experiences between 6-14 days of migraine/migrainous headaches per month at baseline (cutoff for chronic migraine is ≥15 days/month) Developmentally able to provide age-appropriate level of assent Has a parent/guardian capable of giving written informed consent Has daily access to a smartphone in order to be able to complete daily study procedures such as diary completion, and to receive text reminders Subject and parent agree the adolescent will not use over-the-counter melatonin, or another migraine preventive medication, while participating in the study Participant and at least one parent speak English Exclusion Criteria: Currently (or within the last 4 weeks) using any medication or device with migraine preventive properties: i.e. topiramate, amitriptyline, nortriptyline, propranolol, metoprolol, sodium valproate, gabapentin, flunarizine, methysergide, riboflavin, butterbur, coenzyme Q10, or the Cefaly TENS device. For onabotulinum toxin, they will have to have been off it for at least three months Use of other sleep medication or sedating medication, such as benzodiazepines, trazodone, or melatonin receptor agonists History of allergy or adverse event with previous use of exogenous melatonin Previous ineffective trial of melatonin 3 mg nightly for migraine prevention, where the trial duration was at least three months in duration Inability to swallow pills, if this inability persists after instruction on pill-swallowing techniques History of epilepsy or seizure Overuse of acute headache medications, wherein medication overuse is defined33 as ≥4 days per month of barbiturate containing compounds, ≥10 days per month of opioid containing compounds, or ≥10 days per month of triptans or ergot-containing compounds. Those using non-specific analgesics ≥15 days per month would also be excluded Adolescent does not have the cognitive capacity to give verbal assent to participate, or the investigator thinks the adolescent does not have the cognitive capacity to complete the diary, even with parental assistance For females: Pregnancy, lactating or planning to become pregnant during the study. For males: planning to father a child during the study Abnormal neurologic examination findings Serious medical illness of any kind; seriousness as judged by the investigator The investigator does not think the participant can comply with study procedures, or does not think it is medically appropriate for the participant to be in the study

Ages Eligible for Study
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Minimum Age: 12 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Melatonin<br>Group randomized to melatonin 3 mg orally nightly | Drug: Melatonin<br>* Taken at 9 PM or 1 hour before bedtime, whichever is earlier<br>* Other names: Rugby melatonin;|
| Placebo Comparator: Placebo<br>Group randomized to placebo orally nightly | Other: Placebo<br>* Matching placebo taken at 9 PM or 1 hour before bedtime, whichever is earlier<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Migraine/Migrainous Days Per 28 Day Period | Number of Migraine/Migrainous Days Per 28 Day Period in melatonin group and placebo group as measured using an online/mobile device headache diary. | final 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Minutes to Sleep Onset | Number of minutes to sleep onset as measured by a FitBit. | 16 weeks | 
| Number of Participants Recruited From Each Recruitment Strategy | Each recruitment strategy will be analyzed for number of participants successfully enrolled. | During the enrollment period, approximately 1 year | 
| Medication Adherence as Measured by Number of Openings Per Participant | eCAP tack caps will be used to measure medication adherence and the number of openings will be recorded per participant. | during the At Home Active Study Period or Weeks 5-16 | 
| Headache Diary Compliance Rate | Number of participants that had ≥85% headache diary compliance during weeks 12-16 of the study. | Weeks 12-16 of the study |