Migraine in Adolescents
Conditions
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.
Detailed description
This is a pilot randomized controlled trial of melatonin vs. placebo for migraine prevention in adolescents 12-17 years old. The main goal of this pilot study is to estimate variance in the outcome measures to help with planning the future fully powered study. Participants will have an in person enrollment visit, followed by phone follow up visits and headache diary data collection via smart phone or internet.
Interventions
DRUGMelatonin
Taken at 9 PM or 1 hour before bedtime, whichever is earlier
OTHERPlacebo
Matching placebo taken at 9 PM or 1 hour before bedtime, whichever is earlier
Sponsors
University of California, Los Angeles
Amy Gelfand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. 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 2. Resides in California 3. Headache fulfills International Classification for Headache Disorders, Third Edition (beta version)33 criteria for episodic migraine (with or without aura) in adolescents 4. Has been experiencing episodic headaches for at least six months 5. Experiences between 6-14 days of migraine/migrainous headaches per month at baseline (cutoff for chronic migraine is ≥15 days/month) 6. Developmentally able to provide age-appropriate level of assent 7. Has a parent/guardian capable of giving written informed consent 8. 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 9. Subject and parent agree the adolescent will not use over-the-counter melatonin, or another migraine preventive medication, while participating in the study 10. Participant and at least one parent speak English
Exclusion criteria
1. 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 2. Use of other sleep medication or sedating medication, such as benzodiazepines, trazodone, or melatonin receptor agonists 3. History of allergy or adverse event with previous use of exogenous melatonin 4. Previous ineffective trial of melatonin 3 mg nightly for migraine prevention, where the trial duration was at least three months in duration 5. Inability to swallow pills, if this inability persists after instruction on pill-swallowing techniques 6. History of epilepsy or seizure 7. 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 8. 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 9. For females: Pregnancy, lactating or planning to become pregnant during the study. For males: planning to father a child during the study 10. Abnormal neurologic examination findings 11. Serious medical illness of any kind; seriousness as judged by the investigator 12. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Migraine/Migrainous Days Per 28 Day Period | final 4 weeks of treatment | Number of Migraine/Migrainous Days Per 28 Day Period in melatonin group and placebo group as measured using an online/mobile device headache diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Minutes to Sleep Onset | 16 weeks | Number of minutes to sleep onset as measured by a FitBit. |
| Number of Participants Recruited From Each Recruitment Strategy | During the enrollment period, approximately 1 year | Each recruitment strategy will be analyzed for number of participants successfully enrolled. |
| Medication Adherence as Measured by Number of Openings Per Participant | during the At Home Active Study Period or Weeks 5-16 | eCAP tack caps will be used to measure medication adherence and the number of openings will be recorded per participant. |
| Headache Diary Compliance Rate | Weeks 12-16 of the study | Number of participants that had ≥85% headache diary compliance during weeks 12-16 of the study. |
Countries
United States
Participant flow
Pre-assignment details
There was a 28 day baseline run-in prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Melatonin Group randomized to melatonin 3 mg orally nightly
Melatonin: Taken at 9 PM or 1 hour before bedtime, whichever is earlier | 13 |
| Placebo Group randomized to placebo orally nightly
Placebo: Matching placebo taken at 9 PM or 1 hour before bedtime, whichever is earlier | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Placebo | Melatonin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 13 Participants | 13 Participants | 26 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 14.1 years STANDARD_DEVIATION 1.7 | 15 years STANDARD_DEVIATION 1.2 | 14.5 years STANDARD_DEVIATION 1.5 |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 6 / 13 | 4 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
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.
Time frame: final 4 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Number of Migraine/Migrainous Days Per 28 Day Period | 3.6 days | Standard Error 0.9 |
| Placebo | Number of Migraine/Migrainous Days Per 28 Day Period | 4.9 days | Standard Error 1.7 |
Secondary
Headache Diary Compliance Rate
Number of participants that had ≥85% headache diary compliance during weeks 12-16 of the study.
Time frame: Weeks 12-16 of the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Melatonin | Headache Diary Compliance Rate | 11 Participants |
| Placebo | Headache Diary Compliance Rate | 10 Participants |
Secondary
Medication Adherence as Measured by Number of Openings Per Participant
eCAP tack caps will be used to measure medication adherence and the number of openings will be recorded per participant.
Time frame: during the At Home Active Study Period or Weeks 5-16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Medication Adherence as Measured by Number of Openings Per Participant | 39 Mean Number of Openings | Standard Deviation 27 |
| Placebo | Medication Adherence as Measured by Number of Openings Per Participant | 60 Mean Number of Openings | Standard Deviation 28 |
Secondary
Number of Minutes to Sleep Onset
Number of minutes to sleep onset as measured by a FitBit.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Number of Minutes to Sleep Onset | 15.2 minutes | Standard Deviation 10.7 |
| Placebo | Number of Minutes to Sleep Onset | 17.2 minutes | Standard Deviation 12 |
Secondary
Number of Participants Recruited From Each Recruitment Strategy
Each recruitment strategy will be analyzed for number of participants successfully enrolled.
Time frame: During the enrollment period, approximately 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Melatonin | Number of Participants Recruited From Each Recruitment Strategy | Clinic recruitment | 6 Participants |
| Melatonin | Number of Participants Recruited From Each Recruitment Strategy | Newspaper advertising | 3 Participants |
| Melatonin | Number of Participants Recruited From Each Recruitment Strategy | Social media advertising (eg, Facebook and Google+ | 11 Participants |
| Melatonin | Number of Participants Recruited From Each Recruitment Strategy | Electronic medical record letter invitation | 10 Participants |
| Melatonin | Number of Participants Recruited From Each Recruitment Strategy | Other | 1 Participants |