Clinical trial NCT03150797: Melatonin for Adolescent Migraine Prevention Study
Official title: Melatonin for Adolescent Migraine Prevention Study (The MAP Study).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Migraine
Keywords: UCSF
UCLA
melatonin
migraine
headache
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
First posted: 2017-05-12
Enrollment: 72
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 10-17-inclusive
2. Weight ≥40 kg, so as not to require mg/kg based dosing
3. Meets International Classification of Headache Disorders III beta1 criteria for migraine in children/adolescents (international standard diagnostic criteria for research)
4. Lives in the state of California- to allow shipping of study medication from our pharmacy
5. Has at least one parent who speaks English-in order to ensure good communication with study team by phone
6. Has daily access to a smartphone in order to provide daily headache diary data
7. A Parent/Guardian consents and the adolescent is cognitively capable of giving assent to participate
8. 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
9. Willing to not use OTC melatonin or change migraine preventives during the trial
10. 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:

1. Continuous headache
2. History of seizures/epilepsy
3. Pregnant/lactating
4. 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
5. If in the investigator's opinion there is a medical or psychiatric concern that makes them think the participant should not participate
6. 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:

1. 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.
2. 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.

Primary outcomes:
measure: Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Participants vs. Placebo.
timeFrame: weeks 5-8 of randomized treatment phase
Secondary outcomes:
measure: Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Placebo.
timeFrame: Weeks 5-8 of randomized treatment phase.
measure: Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 3 mg vs. Placebo.
timeFrame: Weeks 5-8 of randomized treatment phase.
measure: Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Melatonin 3 mg.
timeFrame: Weeks 5-8 of randomized treatment phase.
measure: 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.
timeFrame: Weeks 5-8 of single-blind treatment phase to weeks 5-8 of randomized treatment phase.
measure: 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.
timeFrame: Weeks 5-8 of randomized treatment phase.
measure: 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.
timeFrame: Weeks 5-8 of randomized treatment phase.
measure: 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.
timeFrame: Weeks 5-8 of randomized treatment phase.
measure: 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.
timeFrame: Weeks 5-8 of randomized treatment phase.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Headache Research and Treatment Program
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco, (UCSF)
state: California
Study officials:
affiliation: University of California, San Francisco
name: Amy A Gelfand, MD
role: PRINCIPAL_INVESTIGATOR
References:
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