Vitamin K2 Supplementation in Adult Episodic Migraine

Study Overview
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Brief Summary
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Migraine is a debilitating illness and a major cause of disability in the world. It is highly prevalent, especially among women. Vitamin supplementation is a potential therapeutic option for migraines that remains largely under-explored. Several studies have shown that people with migraine tend to have higher arterial stiffness than people without migraine. Vitamin K2 deficiency is an important mediator of arterial stiffness and calcification due to decreased carboxylation of matrix Gla protein (MGP). Supplementation reverses these changes and improves vascular health in patients with end stage renal disease according to previous studies. Therefore, vitamin K2 supplementation could serve a potential role in migraine patients. The purpose of the study is to test the effect of vitamin K2 on decreasing the frequency of migraine attacks and decreasing arterial stiffness. The population will be recruited from the neurology clinic at LAU Medical Center-Rizk Hospital and will constitute of adult patients. They will be randomized to receive either the supplement of vitamin K2 or a placebo for the duration of 6 months. Laboratory tests and arterial stiffness measurements will be done at the beginning, middle, and at the end of the study for comparison.

Official Title
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Efficacy of Vitamin K2 Supplementation in Adult Episodic Migraine

Conditions
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Migraine Headache, Arterial Stiffness, Vitamin K Deficiency

Intervention / Treatment
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* Dietary Supplement: Vitamin K2 or menaquinone-7
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 years or above History of episodic migraine with or without aura since > 12 months according to the ICHD-3 criteria. Migraine frequency from 4-14 days per month over the 3 months prior to screening. Migraine frequency from 4-14 days per month during the baseline period of assessment. Successful completion of the migraine diary during the baseline evaluation period. Exclusion Criteria: Migraine patients with superimposed tension type or other forms of primary headaches Patients who are currently on any of the migraine prophylactic treatments (Sodium valproate, Topiramate, Beta-blockers, Tricyclic antidepressants, SRNI, Flunarizine, Verapamil, Lisinopril, Candesartan) Patients who have been on any of the previously listed medications within 3 months of screening Patient who takes the following medications: Ergotamine or Triptans > 10 days per month NSAIDs or paracetamol > 15 days per month Opioids more than 4 days per month Patients on anticoagulants Other active chronic pain syndromes (i.e. fibromyalgia, painful peripheral neuropathy, post-herpetic neuralgia…) History of hypersensitivity to the vitamin K2 History of soy protein, cheese, eggs and meat allergy History of thrombotic events Diagnosed coagulopathy or any condition related to coagulation Cardiovascular event in the past month Current or planned pregnancy Lactation Inability to tolerate oral medications Known intestinal malabsorption or hypomotility syndromes Atrial fibrillation Active malignancy Any acute illness in the past month

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Migraine subjects will be randomized to receive either the supplement of vitamin K2 or a placebo for the duration of 6 months.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (MK7) Arm<br>This corresponds to the sub-group of subjects who will receive the supplement (vitamin K2 or Menaquinone-7). | Dietary Supplement: Vitamin K2 or menaquinone-7<br>* Vitamin K2 (MK7) 360 mcg/day orally once daily for 6 months<br>* Other names: MenaQ7;|
| Placebo Comparator: Control Arm<br>This corresponds to the sub-group of subjects who will receive placebo. | Other: Placebo<br>* Placebo pills will be administered orally once daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of monthly migraine days | Effect of Vitamin K2 supplementation on the changes from baseline in monthly migraine days as compared to placebo. This will be assessed clinically using a questionnaire to be administered at the start, monthly, and at the end of the study (6 months) about frequency and number of migraine days per month. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in the headache impact score (HIT-6) as compared to placebo. |  | 6 months | 
| Changes from baseline in monthly severe migraine days. | Changes from baseline in monthly severe migraine days as defined by a visual analogue scale rating above 7, as compared to placebo. | 6 months | 
| Changes from baseline on the modified migraine disability assessment (MIDAS) score as compared to placebo. |  | 6 months | 
| Changes from baseline on the modified migraine physical function impact diary (MPFID) as compared to placebo. |  | 6 months | 
| Changes from baseline on the quality of life as measure by the EuroQoL compared to placebo. |  | 6 months | 
| Changes from baseline of arterial stiffness level. | Changes of arterial stiffness level assessed by measuring the cfPWV using Complior Analyze. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Arterial stiffness, Vitamin K deficiency, Migraine attack