Clinical trial NCT02344316: Bringing Relief to Adolescents Naturally Using Melatonin for Migraine
Official title: Melatonin for Migraine Prevention in Adolescents: A Pilot Remote Trial: "The BRAiN-M Study"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine in Adolescents
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
First posted: 2015-01-22
Enrollment: 31
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Number of Migraine/Migrainous Days Per 28 Day Period
timeFrame: final 4 weeks of treatment
Secondary outcomes:
measure: Number of Minutes to Sleep Onset
timeFrame: 16 weeks
measure: Number of Participants Recruited From Each Recruitment Strategy
timeFrame: During the enrollment period, approximately 1 year
measure: Medication Adherence as Measured by Number of Openings Per Participant
timeFrame: during the "At Home Active Study Period" or Weeks 5-16
measure: Headache Diary Compliance Rate
timeFrame: Weeks 12-16 of the study
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: UCSF Pediatric Brain Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Amy A Gelfand, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Masruha MR, Lin J, de Souza Vieira DS, Minett TS, Cipolla-Neto J, Zukerman E, Vilanova LC, Peres MF. Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities. Headache. 2010 Mar;50(3):413-9. doi: 10.1111/j.1526-4610.2009.01547.x. Epub 2009 Oct 8.
citation: Masruha MR, de Souza Vieira DS, Minett TS, Cipolla-Neto J, Zukerman E, Vilanova LC, Peres MF. Low urinary 6-sulphatoxymelatonin concentrations in acute migraine. J Headache Pain. 2008 Aug;9(4):221-4. doi: 10.1007/s10194-008-0047-5. Epub 2008 Jul 2.
citation: Peres MF, Masruha MR, Zukerman E, Moreira-Filho CA, Cavalheiro EA. Potential therapeutic use of melatonin in migraine and other headache disorders. Expert Opin Investig Drugs. 2006 Apr;15(4):367-75. doi: 10.1517/13543784.15.4.367.
citation: Peres MF, Zukerman E, da Cunha Tanuri F, Moreira FR, Cipolla-Neto J. Melatonin, 3 mg, is effective for migraine prevention. Neurology. 2004 Aug 24;63(4):757. doi: 10.1212/01.wnl.0000134653.35587.24. No abstract available.
citation: Peres MF, Sanchez del Rio M, Seabra ML, Tufik S, Abucham J, Cipolla-Neto J, Silberstein SD, Zukerman E. Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):747-51. doi: 10.1136/jnnp.71.6.747.
citation: Fallah R, Shoroki FF, Ferdosian F. Safety and efficacy of melatonin in pediatric migraine prophylaxis. Curr Drug Saf. 2015;10(2):132-5. doi: 10.2174/1574886309666140605114614.