Clinical trial NCT05943457: Vitamin K2 Supplementation in Adult Episodic Migraine
Official title: Efficacy of Vitamin K2 Supplementation in Adult Episodic Migraine
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Migraine Headache
Arterial Stiffness
Vitamin K Deficiency
Keywords: Migraine
Arterial stiffness
Vitamin K deficiency
Migraine attack
Lead sponsor: Lebanese American University
Sponsor class: OTHER
Collaborators: name: Lesaffre International
name: Omicron Pharmaceuticals
First posted: 2023-07-13
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Migraine subjects will be randomized to receive either the supplement of vitamin K2 or a placebo for the duration of 6 months.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Changes of monthly migraine days
timeFrame: 6 months
Secondary outcomes:
measure: Changes from baseline in the headache impact score (HIT-6) as compared to placebo.
timeFrame: 6 months
measure: Changes from baseline in monthly severe migraine days.
timeFrame: 6 months
measure: Changes from baseline on the modified migraine disability assessment (MIDAS) score as compared to placebo.
timeFrame: 6 months
measure: Changes from baseline on the modified migraine physical function impact diary (MPFID) as compared to placebo.
timeFrame: 6 months
measure: Changes from baseline on the quality of life as measure by the EuroQoL compared to placebo.
timeFrame: 6 months
measure: Changes from baseline of arterial stiffness level.
timeFrame: 6 months
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: Lebanese American University Medical Center - Rizk Hospital
Study officials:
affiliation: Lebanese American University School of Medicine
name: Sola Aoun Bahous, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stovner Lj, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, Steiner T, Zwart JA. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007 Mar;27(3):193-210. doi: 10.1111/j.1468-2982.2007.01288.x.
citation: Kurth T, Winter AC, Eliassen AH, Dushkes R, Mukamal KJ, Rimm EB, Willett WC, Manson JE, Rexrode KM. Migraine and risk of cardiovascular disease in women: prospective cohort study. BMJ. 2016 May 31;353:i2610. doi: 10.1136/bmj.i2610.
citation: Mozos I, Stoian D, Luca CT. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness. Dis Markers. 2017;2017:8784971. doi: 10.1155/2017/8784971. Epub 2017 Jan 12.
citation: Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012 Feb;59(2):186-95. doi: 10.1053/j.ajkd.2011.10.041. Epub 2011 Dec 9.
citation: Mansour AG, Hariri E, Daaboul Y, Korjian S, El Alam A, Protogerou AD, Kilany H, Karam A, Stephan A, Bahous SA. Vitamin K2 supplementation and arterial stiffness among renal transplant recipients-a single-arm, single-center clinical trial. J Am Soc Hypertens. 2017 Sep;11(9):589-597. doi: 10.1016/j.jash.2017.07.001. Epub 2017 Jul 13.
citation: Mansour AG, Ahdab R, Daaboul Y, Korjian S, Morrison DA, Hariri E, Salem M, El Khoury C, Riachi N, Aoun Bahous S. Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case-Control Study. Headache. 2020 Mar;60(3):589-599. doi: 10.1111/head.13715. Epub 2019 Nov 25.