Bringing Relief to Adolescents Naturally Using Melatonin for Migraine

NCT02344316 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 14-14251
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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.

Conditions

Migraine in Adolescents

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Minutes to Sleep Onset

  16 weeks

• Number of Participants Recruited From Each Recruitment Strategy

  During the enrollment period, approximately 1 year

• Medication Adherence as Measured by Number of Openings Per Participant

  during the "At Home Active Study Period" or Weeks 5-16

• Headache Diary Compliance Rate

  Weeks 12-16 of the study

Study Arms (2)

Melatonin

ACTIVE COMPARATOR

Group randomized to melatonin 3 mg orally nightly

Drug: Melatonin

Placebo

PLACEBO COMPARATOR

Group randomized to placebo orally nightly

Other: Placebo

Interventions

Melatonin DRUG

Taken at 9 PM or 1 hour before bedtime, whichever is earlier

Also known as: Rugby melatonin

Melatonin

Placebo OTHER

Matching placebo taken at 9 PM or 1 hour before bedtime, whichever is earlier

Placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amy Gelfand: lead
• University of California, Los Angeles: collaborator

Study Sites (2)

UCLA Headache Research and Treatment Program

Los Angeles, California, 90077, United States

Location

UCSF Pediatric Brain Center

San Francisco, California, 94158, United States

Location

Related Publications (6)

• 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.

  PMID: 19817880 BACKGROUND

• 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.

  PMID: 18594760 BACKGROUND

• 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.

  PMID: 16548786 BACKGROUND

• 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.

  PMID: 15326268 BACKGROUND

• 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.

  PMID: 11723194 BACKGROUND

• 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.

  PMID: 24909684 BACKGROUND

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Amy Gelfand, MD
• Organization: UCSF Pediatric Headache Program

Amy.Gelfand@ucsf.edu

415-885-7832

Study Officials

• Amy A Gelfand, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: January 22, 2015
• Study Start: May 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: September 9, 2021
• Results First Posted: September 9, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)