Melatonin for Adolescent Migraine Prevention Study

Migraine Clinical Trial

— MAP  

Official title:

Melatonin for Adolescent Migraine Prevention Study (The MAP Study).

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03150797
• Other study ID #: 16-19623
• Status: Terminated
• Phase: Phase 2
• Start date: August 2, 2017
• Est. completion date: December 1, 2019

Study information

• Verified date: September 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Melatonin
Melatonin
• Placebo oral capsule
Placebo

Locations

Country	Name	City	State
United States	UCLA Headache Research and Treatment Program	Los Angeles	California
United States	University of California, San Francisco, (UCSF)	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Amy Gelfand	University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).	Weeks 5-8 of randomized treatment phase.
Secondary	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.	Weeks 5-8 of randomized treatment phase.
Secondary	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.	Weeks 5-8 of randomized treatment phase.
Secondary	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).	Weeks 5-8 of single-blind treatment phase to weeks 5-8 of randomized treatment phase.
Secondary	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.	Weeks 5-8 of randomized treatment phase.
Secondary	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	Weeks 5-8 of randomized treatment phase.
Secondary	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.	Weeks 5-8 of randomized treatment phase.
Secondary	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.	Weeks 5-8 of randomized treatment phase.