Melatonin for Adolescent Migraine Prevention Study

Study Overview
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Brief Summary
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This will be a randomized, multi-site double-blind placebo-controlled trial of melatonin (2 different dosing arms) vs. placebo for migraine prevention in adolescents. We intend to enroll approximately 210 participants over 15 months at two sites: UCLA and UCSF. The duration of participation for each participant will be 4 months.

Detailed Description
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Participation includes 16 weeks of daily headache diary recording and taking the study pill every night, 1-2 hours before bed. Aside from the initial 1 hour enrollment visit, all remaining study procedures will be completed from home. During the enrollment visit, history of migraine, questionnaires, a neurologic and physical exam (including weight, blood pressure, pulse, and respiratory rate) will be performed. Girls who have had their first period will undergo a urine pregnancy test and will be instructed to use birth control if they are sexually active. For the first 8 week phase, participants will be instructed to take one study pill every night, 1-2 hours before bedtime and complete a daily headache diary from a smartphone. Phone call check-ins will occur at week 4 and week 8. After the first 8 weeks of the study, participants who are eligible for the second phase of the study will be notified by study staff and will be sent the next set of study pills. Again, participants will be instructed to take the study pill every night, 1-2 hours before bedtime and complete a diary entry every evening. Phone call check-ins will occur at week 12 and week 16. At the final 16 week phone call, additional questionnaires and study completion feedback will be collected.

Official Title
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Melatonin for Adolescent Migraine Prevention Study (The MAP Study).

Conditions
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Migraine

Intervention / Treatment
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* Drug: Melatonin
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 10-17-inclusive Weight ≥40 kg, so as not to require mg/kg based dosing Meets International Classification of Headache Disorders III beta1 criteria for migraine in children/adolescents (international standard diagnostic criteria for research) Lives in the state of California- to allow shipping of study medication from our pharmacy Has at least one parent who speaks English-in order to ensure good communication with study team by phone Has daily access to a smartphone in order to provide daily headache diary data A Parent/Guardian consents and the adolescent is cognitively capable of giving assent to participate Either not on a migraine preventive medication, or if on one the dose has been stable for at least 4 weeks prior to enrollment, or are willing to wait to start the study until they have reached a stable dose for 4 weeks Willing to not use OTC melatonin or change migraine preventives during the trial Has ≥1 headache day per week, or 4-28 days of headache in a 28-day period Episodic headaches have been present for a minimum of 6 months-This lowers the likelihood of a secondary cause of headaches Exclusion Criteria: Continuous headache History of seizures/epilepsy Pregnant/lactating Concomitant opioid or barbiturate overuse, wherein overuse is defined as ≥4 days per month of barbiturate containing compounds, ≥10 days per month of opioid containing compounds as these may impact sleepiness scales If in the investigator's opinion there is a medical or psychiatric concern that makes them think the participant should not participate Inability to swallow pills after teaching and practice History of nocturnal asthma, as evidenced by a having a diagnosis of asthma and symptoms that manifest as nighttime awakening due to cough, wheeze, and/or shortness of breath Randomization Criteria: Had 4-28 migraine/migrainous days in the 28-day period of weeks 5-8 of single-blind placebo treatment phase, but not continuous headache. At least 80% compliance with headache diary (i.e. at least 23 headache diary days) during weeks 5-8 of single-blind placebo treatment phase.

Ages Eligible for Study
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Minimum Age: 10 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin 3mg<br>Melatonin 3mg | Drug: Melatonin<br>* Melatonin<br>|
| Experimental: Melatonin 6mg<br>Melatonin 6mg | Drug: Melatonin<br>* Melatonin<br>|
| Placebo Comparator: Placebo oral capsule<br>Placebo | Drug: Placebo oral capsule<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Participants vs. Placebo. | Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin treated participants vs. placebo. (Ultimately, as the data were not normally distributed, medians were more appropriate). | weeks 5-8 of randomized treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Placebo. | Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 6 mg vs. placebo. (Medians reported when data were not normally distributed). | Weeks 5-8 of randomized treatment phase. | 
| Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 3 mg vs. Placebo. | Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 3 mg vs. placebo. | Weeks 5-8 of randomized treatment phase. | 
| Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Melatonin 3 mg. | Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 6 mg vs. melatonin 3 mg. | Weeks 5-8 of randomized treatment phase. | 
| Change in Mean Migraine/Migrainous Days From Weeks 5-8 of Single-blind Treatment Phase to Weeks 5-8 of Randomized Treatment Phase for Each Group. | Change in mean migraine/migrainous days from weeks 5-8 of single-blind treatment phase to weeks 5-8 of randomized treatment phase for each group. (Medians reported when data were not normally distributed). | Weeks 5-8 of single-blind treatment phase to weeks 5-8 of randomized treatment phase. | 
| Mean PedMIDAS (Pediatric Migraine Disability Assessment Score) in Weeks 5-8 of Randomized Treatment Phase in Each Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons. | Mean PedMIDAS (headache related disability score) in weeks 5-8 of randomized treatment phase in each melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. PedMIDAS is a 6 question instrument for measuring headache related disability in children and adolescents. | Weeks 5-8 of randomized treatment phase. | 
| Mean CASQ (Cleveland Adolescent Sleepiness Questionnaire) Score in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons. | Mean CASQ score in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. The CASQ is a 16-question instrument that uses Likert-like responses and has a score range from 16-80; higher scores indicate greater sleepiness | Weeks 5-8 of randomized treatment phase. | 
| Number of Days Acute Medication is Used in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons. | Number of days acute medication is used in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. This refers to the number of days that medication for the acute treatment of headache was used during the time frame. | Weeks 5-8 of randomized treatment phase. | 
| Number of Headache Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons. | Number of headache days in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. This refers to number of headache days during the time period--regardless of whether they were migraine or not. | Weeks 5-8 of randomized treatment phase. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UCSF, UCLA, melatonin, migraine, headache