Melatonin for Adolescent Migraine Prevention Study

NCT03150797 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-19623
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

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.

Conditions

Migraine

Keywords

UCSF; UCLA; melatonin; migraine; headache

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Placebo.

  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.

  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.

  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.

  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.

  Weeks 5-8 of randomized treatment phase.

Study Arms (3)

Melatonin 3mg

EXPERIMENTAL

Melatonin 3mg

Drug: Melatonin

Melatonin 6mg

EXPERIMENTAL

Melatonin 6mg

Drug: Melatonin

Placebo oral capsule

PLACEBO COMPARATOR

Placebo

Drug: Placebo oral capsule

Interventions

Melatonin DRUG

Melatonin

Melatonin 3mg; Melatonin 6mg

Placebo oral capsule DRUG

Placebo

Placebo oral capsule

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

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

University of California, San Francisco, (UCSF)

San Francisco, California, 94158, United States

Location

Related Publications (12)

• Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658. No abstract available.

  PMID: 23771276 BACKGROUND

• Bigal ME, Lipton RB, Winner P, Reed ML, Diamond S, Stewart WF; AMPP advisory group. Migraine in adolescents: association with socioeconomic status and family history. Neurology. 2007 Jul 3;69(1):16-25. doi: 10.1212/01.wnl.0000265212.90735.64.

  PMID: 17606878 BACKGROUND

• Arruda MA, Bigal ME. Migraine and migraine subtypes in preadolescent children: association with school performance. Neurology. 2012 Oct 30;79(18):1881-8. doi: 10.1212/WNL.0b013e318271f812.

  PMID: 23109652 BACKGROUND

• Chang YS, Lin MH, Lee JH, Lee PL, Dai YS, Chu KH, Sun C, Lin YT, Wang LC, Yu HH, Yang YH, Chen CA, Wan KS, Chiang BL. Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance: A Randomized Clinical Trial. JAMA Pediatr. 2016 Jan;170(1):35-42. doi: 10.1001/jamapediatrics.2015.3092.

  PMID: 26569624 BACKGROUND

• Goncalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1127-32. doi: 10.1136/jnnp-2016-313458. Epub 2016 May 10.

  PMID: 27165014 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

• 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

• Alstadhaug KB, Odeh F, Salvesen R, Bekkelund SI. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology. 2010 Oct 26;75(17):1527-32. doi: 10.1212/WNL.0b013e3181f9618c.

  PMID: 20975054 BACKGROUND

• Bougea A, Spantideas N, Lyras V, Avramidis T, Thomaidis T. Melatonin 4 mg as prophylactic therapy for primary headaches: a pilot study. Funct Neurol. 2016 Jan-Mar;31(1):33-7. doi: 10.11138/fneur/2016.31.1.033.

  PMID: 27027892 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

• Miano S, Parisi P, Pelliccia A, Luchetti A, Paolino MC, Villa MP. Melatonin to prevent migraine or tension-type headache in children. Neurol Sci. 2008 Sep;29(4):285-7. doi: 10.1007/s10072-008-0983-5. Epub 2008 Sep 20.

  PMID: 18810607 BACKGROUND

• Spilsbury JC, Drotar D, Rosen CL, Redline S. The Cleveland adolescent sleepiness questionnaire: a new measure to assess excessive daytime sleepiness in adolescents. J Clin Sleep Med. 2007 Oct 15;3(6):603-12.

  PMID: 17993042 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders; Headache

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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: Dr. Amy Gelfand
• Organization: UCSF

amy.gelfand@ucsf.edu

415-502-1914

Study Officials

• Amy A Gelfand, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Pediatric Headache UCSF Benioff Children's Hospital

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 12, 2017
• Study Start: August 2, 2017
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: October 13, 2023
• Results First Posted: October 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)