To evaluate the effect of vitamin D supplementation on the severity, duration and frequency of headache attacks in adolescents with migraine.
Design
A randomized; parallel group; double-blind (outcome assessor and statistical analyst blinded); phase 3 clinical trial of 112 patients. Randomization was performed using a permuted block method with a block size of 4 to ensure concealed allocation sequence.
Settings and conduct
Setting: Pediatric Neurology Clinic of ValiAsr Hospital of Birjand; one hundred and twelve adolescents randomized into two groups; outcome assessor and statistical analyst are blinded.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Age twelve to eighteen years; migraine diagnosis; stable Sodium Valproate dose. Exclusion criteria: Renal disease; recent supplement use; high serum calcium.
Intervention groups
Intervention group: Receiving routine treatment with Sodium Valproate tablets; plus weekly consumption of one Vitamin D softgel containing 50000 International Units for 10 weeks.
Control group: Receiving routine treatment with Sodium Valproate tablets only; without receiving any additional supplements or placebos.
Main outcome variables
Mean headache intensity score; time of measurement at baseline and 10 weeks after the initiation of the intervention; measurement tool is the Visual Analog Scale from score 0 to 10.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20251116068013N1
Registration date:2026-05-13, 1405/02/23
Registration timing:prospective
Last update:2026-05-13, 1405/02/23
Update count:0
Registration date
2026-05-13, 1405/02/23
Registrant information
Name
mahya hosseini
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 56 3239 5000
Email address
mahyahosseini@bums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2026-06-05, 1405/03/15
Expected recruitment end date
2026-10-07, 1405/07/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Investigating the effect of vitamin D on headache severity in adolescents with migraine
Public title
Investigating the effect of vitamin D on headache severity in adolescents
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Adolescents aged between 10 and 18 years
Definitive diagnosis of migraine by a pediatric neurologist based on ICHD-3 criteria
Serum vitamin D levels less than 30 ng/ml (deficiency or insufficiency)
Willingness to participate and providing informed consent by parents or legal guardians
Absence of chronic underlying diseases (cardiac, renal, or hepatic)
Exclusion criteria:
Affliction with chronic systemic diseases (including cardiovascular, renal, hepatic diseases, and hyperthyroidism or hypothyroidism)
Use of vitamin D supplements in the past three months
Consumption of medications affecting vitamin D metabolism (such as specific anticonvulsants or corticosteroids)
Presence of morbid obesity (Body Mass Index or BMI > 30 kg/m²)
Diagnosis of Diabetes Mellitus
Reluctance of the patient or parents to continue participation at any stage of the study
Occurrence of severe adverse effects or hypersensitivity to vitamin D supplementation
Age
From 10 years old to 18 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Outcome assessor
Data analyser
Sample size
Target sample size:
112
Randomization (investigator's opinion)
Randomized
Randomization description
Participants will be assigned to either the intervention or control group using a Block Randomization method with a block size of 4 and an allocation ratio of 1:1. The randomization sequence will be generated by an independent individual (not involved in clinical care or assessment) using computer-generated random numbers. To ensure Allocation Concealment, sequentially numbered, opaque, sealed envelopes will be used. Upon enrollment, each participant will be assigned a serial number and will receive the corresponding envelope to determine their group assignment.
Blinding (investigator's opinion)
Double blinded
Blinding description
To implement blinding, vitamin D supplements will be provided in identical packaging so that the participants (adolescents) remain unaware of their group assignments. Furthermore, the outcome assessor (pediatric neurologist), who evaluates headache severity using the VAS scale and records the frequency of attacks at the end of the third month, will be blinded to the group allocations. Additionally, the statistical analyst will remain blinded to the group identities until the completion of the data analysis process.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committee of Birjand University of Medical Sciences
Street address
Ghafari Blvd
City
Birjand
Province
South Khorasan
Postal code
9717853577
Approval date
2025-05-14, 1404/02/24
Ethics committee reference number
IR.BUMS.REC.1404.075
Health conditions studied
1
Description of health condition studied
Migraine in children and adolescents
ICD-10 code
G43
ICD-10 code description
Migraine
Primary outcomes
1
Description
Headache intensity
Timepoint
Before intervention (Baseline), 1, 2, and 3 months after the start of interventio
Method of measurement
Visual analogue scale
2
Description
Duration of headache in hours per day
Timepoint
Before intervention and one month after the intervention and two months after intervention and three months after the intervention
Method of measurement
Daily recording with timer
3
Description
Number of the patient’s headache attacks per month
Timepoint
Monthly
Method of measurement
Daily recording
4
Description
Vitamin D
Timepoint
Before and after intervention
Method of measurement
Laboratory measurement of Vitamin D
Secondary outcomes
empty
Intervention groups
1
Description
The intervention group receives 1000 IU of Vitamin D supplement orally per day for 3 months. In addition, routine treatment including Propranolol tablets (20 mg every 12 hours) and Amitriptyline tablets (25 mg at night) is prescribed.
Category
Treatment - Drugs
2
Description
The control group receives only the routine treatment including Propranolol tablets (20 mg every 12 hours) and Amitriptyline tablets (25 mg at night) for 3 months and will not receive Vitamin D supplements.