Vitamin K2 Supplementation in Adult Episodic Migraine

NCT05943457 | Recruiting

• 1 other identifier: MK7-003
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine Headache; Arterial Stiffness; Vitamin K Deficiency

Keywords

Migraine; Arterial stiffness; Vitamin K deficiency; Migraine attack

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Changes from baseline in the headache impact score (HIT-6) as compared to placebo.

  6 months

• Changes from baseline in monthly severe migraine days.

  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

Study Arms (2)

Intervention (MK7) Arm

EXPERIMENTAL

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

Control Arm

PLACEBO COMPARATOR

This corresponds to the sub-group of subjects who will receive placebo.

Other: Placebo

Interventions

Vitamin K2 or menaquinone-7 DIETARY_SUPPLEMENT

Vitamin K2 (MK7) 360 mcg/day orally once daily for 6 months

Also known as: MenaQ7

Intervention (MK7) Arm

Placebo OTHER

Placebo pills will be administered orally once daily for 6 months

Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sola Aoun Bahous, M.D. Ph.D.: lead
• Lesaffre International: collaborator
• Omicron Pharmaceuticals: collaborator

Study Sites (1)

Lebanese American University Medical Center - Rizk Hospital

Beirut, Beyrouth, 11-3288, Lebanon

RECRUITING

Related Publications (6)

• 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.

  PMID: 17381554 BACKGROUND

• 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.

  PMID: 27247281 BACKGROUND

• 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.

  PMID: 28167849 BACKGROUND

• 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.

  PMID: 22169620 BACKGROUND

• 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.

  PMID: 28756183 BACKGROUND

• 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.

  PMID: 31769041 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders; Vitamin K Deficiency

Interventions

Vitamin K 2; menaquinone 7

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Officials

• Sola Aoun Bahous, MD, PhD

  Lebanese American University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sola Aoun Bahous, MD, PhD

CONTACT

+9613259450; sola.bahous@lau.edu.lb

Cedric Mhaseb, MD

CONTACT

+96176489620; cedric.mhasseb@lau.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, investigators, and analysts will remain blind to the identity of the treatment from the time of randomization until the time of unblinding. The identity of the treatment will be concealed by using placebo pills that are identical in appearance, color, odor and packaging. Unblinding will only occur in the case of a medical emergency and at the conclusion of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Migraine subjects will be randomized to receive either the supplement of vitamin K2 or a placebo for the duration of 6 months.

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 13, 2023
• Study Start: March 6, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: We have a plan to publish the study protocol as soon as possible.

Locations

LE (1)