Melatonin for Adolescent Migraine Prevention Study

NCT ID: NCT03150797

Last Updated: 2023-10-13

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-02

Study Completion Date

2019-12-01

Brief Summary

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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

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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.

Conditions

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Migraine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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Melatonin 3mg

Melatonin 3mg

Group Type EXPERIMENTAL

Melatonin

Intervention Type DRUG

Melatonin

Melatonin 6mg

Melatonin 6mg

Group Type EXPERIMENTAL

Melatonin

Intervention Type DRUG

Melatonin

Placebo oral capsule

Placebo

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Placebo

Interventions

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Melatonin

Melatonin

Intervention Type DRUG

Placebo oral capsule

Placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

10 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, Los Angeles

OTHER

Sponsor Role collaborator

Amy Gelfand

OTHER

Sponsor Role lead

Responsible Party

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Amy Gelfand

Director of Pediatric Headache UCSF Benioff Children's Hospital

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Amy A Gelfand, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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UCLA Headache Research and Treatment Program

Los Angeles, California, United States

Site Status

University of California, San Francisco, (UCSF)

San Francisco, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 23771276 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17606878 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23109652 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26569624 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27165014 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18594760 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19817880 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20975054 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27027892 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24909684 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18810607 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17993042 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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16-19623

Identifier Type: -

Identifier Source: org_study_id

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