Back to resultsMelatonin for Adolescent Migraine Prevention Study (MAP)
Primary Purpose
Migraine
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Melatonin
Placebo oral capsule
Sponsored by
About this trial
This is an interventional prevention trial for Migraine focused on measuring UCSF, UCLA, melatonin, migraine, headache
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- UCLA Headache Research and Treatment Program
- University of California, San Francisco, (UCSF)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Melatonin 3mg
Melatonin 6mg
Placebo oral capsule
Arm Description
Melatonin 3mg
Melatonin 6mg
Placebo
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Placebo.
Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 6 mg vs. placebo. (Medians reported when data were not normally distributed).
Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 3 mg vs. Placebo.
Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 3 mg vs. placebo.
Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Melatonin 3 mg.
Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 6 mg vs. melatonin 3 mg.
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.
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. (Medians reported when data were not normally distributed).
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.
Mean PedMIDAS (headache related disability 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. PedMIDAS is a 6 question instrument for measuring headache related disability in children and adolescents.
Mean CASQ (Cleveland Adolescent Sleepiness Questionnaire) Score in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons.
Mean CASQ score in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. The CASQ is a 16-question instrument that uses Likert-like responses and has a score range from 16-80; higher scores indicate greater sleepiness
Number of Days Acute Medication is Used in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons.
Number of days acute medication is used in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. This refers to the number of days that medication for the acute treatment of headache was used during the time frame.
Number of Headache Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons.
Number of headache days in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. This refers to number of headache days during the time period--regardless of whether they were migraine or not.
Full Information
NCT ID
NCT03150797
First Posted
May 10, 2017
Last Updated
September 20, 2023
Sponsor
Amy Gelfand
Collaborators
University of California, Los Angeles
1. Study Identification
Unique Protocol Identification Number
NCT03150797
Brief Title
Melatonin for Adolescent Migraine Prevention Study
Acronym
MAP
Official Title
Melatonin for Adolescent Migraine Prevention Study (The MAP Study).
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Insufficient Fund
Study Start Date
August 2, 2017 (Actual)
Primary Completion Date
December 1, 2019 (Actual)
Study Completion Date
December 1, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Amy Gelfand
Collaborators
University of California, Los Angeles
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine
Keywords
UCSF, UCLA, melatonin, migraine, headache
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
72 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Melatonin 3mg
Arm Type
Experimental
Arm Description
Melatonin 3mg
Arm Title
Melatonin 6mg
Arm Type
Experimental
Arm Description
Melatonin 6mg
Arm Title
Placebo oral capsule
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Melatonin
Intervention Description
Melatonin
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Participants vs. Placebo.
Description
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).
Time Frame
weeks 5-8 of randomized treatment phase
Secondary Outcome Measure Information:
Title
Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Placebo.
Description
Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 6 mg vs. placebo. (Medians reported when data were not normally distributed).
Time Frame
Weeks 5-8 of randomized treatment phase.
Title
Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 3 mg vs. Placebo.
Description
Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 3 mg vs. placebo.
Time Frame
Weeks 5-8 of randomized treatment phase.
Title
Mean Migraine/Migrainous Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin 6 mg vs. Melatonin 3 mg.
Description
Mean migraine/migrainous days in weeks 5-8 of randomized treatment phase in melatonin 6 mg vs. melatonin 3 mg.
Time Frame
Weeks 5-8 of randomized treatment phase.
Title
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.
Description
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. (Medians reported when data were not normally distributed).
Time Frame
Weeks 5-8 of single-blind treatment phase to weeks 5-8 of randomized treatment phase.
Title
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.
Description
Mean PedMIDAS (headache related disability 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. PedMIDAS is a 6 question instrument for measuring headache related disability in children and adolescents.
Time Frame
Weeks 5-8 of randomized treatment phase.
Title
Mean CASQ (Cleveland Adolescent Sleepiness Questionnaire) Score in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons.
Description
Mean CASQ score in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. The CASQ is a 16-question instrument that uses Likert-like responses and has a score range from 16-80; higher scores indicate greater sleepiness
Time Frame
Weeks 5-8 of randomized treatment phase.
Title
Number of Days Acute Medication is Used in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons.
Description
Number of days acute medication is used in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. This refers to the number of days that medication for the acute treatment of headache was used during the time frame.
Time Frame
Weeks 5-8 of randomized treatment phase.
Title
Number of Headache Days in Weeks 5-8 of Randomized Treatment Phase in Melatonin Treated Group vs. Placebo, and in Each of the Three Pair-wise Group Comparisons.
Description
Number of headache days in weeks 5-8 of randomized treatment phase in melatonin treated group vs. placebo, and in each of the three pair-wise group comparisons. This refers to number of headache days during the time period--regardless of whether they were migraine or not.
Time Frame
Weeks 5-8 of randomized treatment phase.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy A Gelfand, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA Headache Research and Treatment Program
City
Los Angeles
State/Province
California
ZIP/Postal Code
90077
Country
United States
Facility Name
University of California, San Francisco, (UCSF)
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23771276
Citation
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.
Results Reference
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PubMed Identifier
17606878
Citation
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.
Results Reference
background
PubMed Identifier
23109652
Citation
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.
Results Reference
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PubMed Identifier
26569624
Citation
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.
Results Reference
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PubMed Identifier
27165014
Citation
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.
Results Reference
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PubMed Identifier
18594760
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.
Results Reference
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PubMed Identifier
19817880
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.
Results Reference
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PubMed Identifier
20975054
Citation
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.
Results Reference
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Citation
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.
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PubMed Identifier
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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.
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Citation
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.
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Citation
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Results Reference
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Melatonin for Adolescent Migraine Prevention Study
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