Migraine
Conditions
Brief summary
Existing treatments for acute migraine are not effective for all children and adolescents, and can cause side effects. Investigator propose a dose-finding study of melatonin for acute migraine treatment in children and adolescents to determine the best dose to bring forward in a future fully-powered efficacy trial.
Detailed description
This pilot randomized trial is a dose-finding study to determine which dose of melatonin is most effective for treating acute migraine in children and adolescents who have episodic migraine. Investigator will identify the most effective dose to pull forward into a future fully-powered placebo-controlled efficacy study. If both doses are equally effective, Investigator will bring forward the best tolerated dose. If doses are equally well tolerated, Investigator will bring forward the lowest effective dose, as this will minimize cost to families should this treatment become widely adopted.
Interventions
DRUGMelatonin
melatonin
Sponsors
Amy Gelfand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Meet ICHD criteria for episodic migraine in children and adolescents, with at least 1 migraine attack per month on average. 2. Age 3-17 years 3. Dissatisfaction with previous acute treatments, for one or more of the following reasons: a) One or more previously tried acute medications have not been effective, or adequately effective, b) previously tried acute treatments have caused side effects, or C) patient/family would prefer a natural supplement for acute treatment over medication treatment 4. If of driving age, teen participant agrees not to drive for at least 8 hours after treating with melatonin.
Exclusion criteria
1. Allergy or intolerance to melatonin, or to chocolate. 2. Opioid or barbiturate overuse as defined in ICHD 3. Pregnant/lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Visual Analog Scale (VAS) Score | Baseline (Time 0) and 2 hours | Visual Analog Scale (VAS) score ranges from 0-10, measured in cm, 0 indicating no pain and 10 indicating the worst pain. |
Countries
United States
Participant flow
Recruitment details
Recruitment ran from September 25, 2017 until November 5, 2019. Eligibility was assessed by a pediatric headache specialist.
Pre-assignment details
Out of 102 participants who were assessed for eligibility, 84 met inclusion criteria and were randomized to a treatment.
Participants by arm
| Arm | Count |
|---|---|
| Low-Dose Melatonin (mg) melatonin 2mg (equal to or over 40kg)
melatonin 1mg (under 40kg)
Melatonin: melatonin | 42 |
| High-Dose Melatonin (mg) melatonin 8mg (equal to or over 40kg)
melatonin 4mg (under 40kg)
Melatonin: melatonin | 42 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 10 | 12 |
| Overall Study | Non-compliant with study activities | 1 | 2 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Low-Dose Melatonin (mg) | High-Dose Melatonin (mg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 42 Participants | 42 Participants | 84 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 | 11.8 years STANDARD_DEVIATION 3.5 | 11.7 years STANDARD_DEVIATION 3.6 | 11.8 years STANDARD_DEVIATION 3.5 |
| Aura | 10 Participants | 6 Participants | 16 Participants |
| Currently on migraine preventive | 19 Participants | 14 Participants | 33 Participants |
| Headache days per month (self report) | 5.5 days per month STANDARD_DEVIATION 4.1 | 5.8 days per month STANDARD_DEVIATION 3.4 | 5.6 days per month STANDARD_DEVIATION 3.8 |
| Melatonin Dose/Weight | 0.04 mg/kg STANDARD_DEVIATION 0.01 | 0.13 mg/kg STANDARD_DEVIATION 0.03 | 0.08 mg/kg STANDARD_DEVIATION 0.05 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Reason(s) for dissatisfaction with previous acute medications Ineffective | 9 participants | 8 participants | 17 participants |
| Reason(s) for dissatisfaction with previous acute medications Other | 14 participants | 9 participants | 23 participants |
| Reason(s) for dissatisfaction with previous acute medications Prefer natural options | 24 participants | 24 participants | 48 participants |
| Reason(s) for dissatisfaction with previous acute medications Side effects | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 42 participants | 42 participants | 84 participants |
| Sex: Female, Male Female | 23 Participants | 23 Participants | 46 Participants |
| Sex: Female, Male Male | 19 Participants | 18 Participants | 37 Participants |
| Weight (kg) | 45.7 kg STANDARD_DEVIATION 18 | 53.1 kg STANDARD_DEVIATION 25.6 | 49.3 kg STANDARD_DEVIATION 22.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 21 |
| other Total, other adverse events | 13 / 19 | 17 / 21 |
| serious Total, serious adverse events | 0 / 19 | 0 / 21 |
Outcome results
Primary
Change in Mean Visual Analog Scale (VAS) Score
Visual Analog Scale (VAS) score ranges from 0-10, measured in cm, 0 indicating no pain and 10 indicating the worst pain.
Time frame: Baseline (Time 0) and 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-Dose Melatonin (mg) | Change in Mean Visual Analog Scale (VAS) Score | -2.3 cm | Standard Deviation 2.1 |
| High-Dose Melatonin (mg) | Change in Mean Visual Analog Scale (VAS) Score | -2.7 cm | Standard Deviation 2.1 |