Bringing Relief to Adolescents Naturally Using Melatonin for Migraine
Condition: Migraine in Adolescents
MeSH terms: Migraine Disorders
Intervention: Melatonin; Placebo
Intervention description: Taken at 9 PM or 1 hour before bedtime, whichever is earlier; Matching placebo taken at 9 PM or 1 hour before bedtime, whichever is earlier
Intervention MeSH terms: Melatonin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. Resides in California

          3. Headache fulfills International Classification for Headache Disorders, Third Edition
             (beta version)33 criteria for episodic migraine (with or without aura) in adolescents

          4. Has been experiencing episodic headaches for at least six months

          5. Experiences between 6-14 days of migraine/migrainous headaches per month at baseline
             (cutoff for chronic migraine is ≥15 days/month)

          6. Developmentally able to provide age-appropriate level of assent

          7. Has a parent/guardian capable of giving written informed consent

          8. 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

          9. Subject and parent agree the adolescent will not use over-the-counter melatonin, or
             another migraine preventive medication, while participating in the study

         10. Participant and at least one parent speak English

        Exclusion Criteria:

          1. 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

          2. Use of other sleep medication or sedating medication, such as benzodiazepines,
             trazodone, or melatonin receptor agonists

          3. History of allergy or adverse event with previous use of exogenous melatonin

          4. Previous ineffective trial of melatonin 3 mg nightly for migraine prevention, where
             the trial duration was at least three months in duration

          5. Inability to swallow pills, if this inability persists after instruction on
             pill-swallowing techniques

          6. History of epilepsy or seizure

          7. 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

          8. 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

          9. For females: Pregnancy, lactating or planning to become pregnant during the study. For
             males: planning to father a child during the study

         10. Abnormal neurologic examination findings

         11. Serious medical illness of any kind; seriousness as judged by the investigator

         12. 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