A Randomized, Parallel, Double-blind, Placebo-controlled Study of Vitamin D as Prophylactic Treatment for Migraine

Study Overview
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Brief Summary
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The trial is primarily designed to investigate whether treatment with vitamin D may influence migraine in a placebo-controlled, blinded study. The hypothesis is that vitamin D may serve as a prophylactic treatment of migraine. The hypothesis is tested by examining the changes in the pain and symptom patterns associated with migraine by treatment with Vitamin D, by means of quantitative sensory testing, diaries and blood samples for measurement of vitamin D. Other pain biomarkers are also measured to evaluate whether the levels of these biomarkers in the blood is changed by the treatment with vitamin D. The hypothesis here is that levels of those biomarkers will change following the treatment.

Official Title
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A Randomized, Parallel, Double-blind, Placebo-controlled Study of Vitamin D as Prophylactic Treatment for Migraine

Conditions
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Migraine According to International Headache Society (IHS) Criteria (ICHD-II)

Intervention / Treatment
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* Drug: D3 Vitamin ®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between 18 and 65, migraine must have occurred before the age of 50 years. Diagnosed migraine according to International Headache Society (IHS) criteria (ICHD-II) Exclusion Criteria: Other neurological or neurodegenerative disorders Medical conditions that may interfere with the result - violent head trauma, stroke, transient ischemic attacks Musculoskeletal or mental illness Addictive or previous addictive behavior defined as the abuse of cannabis, opioids or other drugs Inability to cooperate Pregnancy or breastfeeding, including women trying to conceive Use of vitamin D supplementation> 10μg In treatment with digoxin or thiazide Patients with osteoarthritis, as they are taking or have taken vitamin D supplements Patients with pre-existing hypercalcemia as vitamin D supplements are contraindicated in these patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D<br>The active treatment consists of vitamin D and is given in tablets of the brand D3 Vitamin ®, supplied by D3 Pharmacy Ltd., Bispensgade 22, 9000 Aalborg. The tablets contain the vitamin D in the form of vitamin D3, also known as cholecalciferol. D3 Vitamin ® consists of small white tablets, which are easy to swallow. D3 Vitamin ® contains 25 micrograms vitamin D3 (colecalciferol) per tablet, equivalent to 1000 IU (International Units). Tablet Excipients: Cellulose, dicalcium phosphate, magnesium stearate, silicon dioxide and talc. Vitamin D3 ® contains no gluten, soy, gelatin or other animal products. | Drug: D3 Vitamin ®<br>* Vitamin D and placebo supplied as tablets in containers of 124. The containers must be kept in dry and not too hot environment. All subjects randomized to vitamin D, will receive 100 micrograms of vitamin D3/day, equivalent to 4000 IU. Vitamin D is administered orally 1 time a day with breakfast.<br>* Other names: D3 Vitamin ®, supplied by D3 Pharmacy Ltd;|
| Placebo Comparator: Placebo<br>Placebo tablets to match D3 Vitamin ®, were produced. They are identical to the D3 Vitamin ® in appearance, ie small white tablets. These tablets do not have a therapeutic effect. Placebo tablets produced and delivered by D3 Pharmacy Ltd., Bispensgade 22, 9000 Aalborg. | Drug: Placebo<br> <br> * Other names: Placebo tablets to match D3 Vitamin ®, produced by D3 Pharmacy Ltd;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of migraine attacks | The primary endpoint is the frequency of migraine attacks. This is estimated from the subjects' listing of attacks in the form of diaries. This is assessed as the number of migraine attacks per 4 weeks (28 days). | every 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of pain during migraine attacks | Evaluation of pain during migraine attacks carried out by the subjects themselves by completing diaries. The diaries trial participants evaluate the pain intensity during an attack using a 1-3 scale, where 1 is mild pain, 2 is moderate pain, and 3 severe pain. | every 4 weeks | 
| Hypersensitivity | allodynia and hyperalgesia (hypersensitivity) assessed by standardized questions about the sensitivity of the skin associated with migraine. | Baseline and every 4 weeks | 
| Migraine Symptoms | Migraine Symptoms, including aura, nausea, light and sound sensitivity are also assessed by trial participants using diaries. | every 4 weeks | 
| Quantitative Sensory Testing | Pain Pressure Threshold and temporal summation are measured. | Every 4 weeks | 
| Measuring levels of a biomarker. Changes in the levels of these biomarkers. | Changes in the levels of these biomarkers are measured: 25(OH)D, 1,25(OH)D, GFAP, S100B, CGRP,Glutamate, Serotonin, Prostaglandin E2 | Baseline and after 6 months treatment (end of trial) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Vitamin D