The Role of Vitamin K on Knee Osteoarthritis Outcomes

The appropriate form and dosing of vitamin K to benefit relevant outcomes in knee osteoarthritis (OA) are not known. In intervention studies for conditions other than knee OA (e.g., prevention of cardiovascular disease), the most commonly used forms and doses include phylloquinone (vitamin K1; 1000µg or 500µg daily) or menaquinone-7 (MK-7 or vitamin K2; 300µg daily). However, whether these doses are adequate to increase vitamin K to levels that ameliorate risk of adverse OA outcomes is not known. Furthermore, although some studies suggest enhanced bioavailability of MK-7 over vitamin K1, as well as extra-hepatic effects, whether this is relevant for an older population with knee OA is not known,

The overall goal of this pilot randomized clinical trial (RCT) is to test different subtypes and doses of vitamin K supplementation in older adults with knee OA and to measure changes in relevant biochemical measures.

Study Overview

• Status: Recruiting
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Other: Placebo; Drug: Vitamin K1 500 µg; Drug: K1 1000 µg; Drug: Vitamin K2 (MK-7) 300 µg

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jean Liew, MD MS; Phone Number: 617 358 9655; Email: jwliew@bu.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston Medical Center, Rheumatology Clinic
      • Contact: Jean Liew, MD MS; Phone Number: 617-358-9655; Email: jwliew@bu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥60 years old
• Clinical diagnosis of knee OA by the treating rheumatologist
• English fluency

Exclusion Criteria:

• Anticoagulation use (including warfarin, dabigatran, rivaroxaban, apixaban)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin K1 500 µg; Participants randomized to this arm will take one Vitamin K1 500 µg pill daily for 4 weeks.	Drug: Vitamin K1 500 µg; One pill daily for 4 weeks.; Other Names: Phylloquinone 500 µg
Experimental: Vitamin K1 1000 µg; Participants randomized to this arm will take one Vitamin K1 1000 µg pill daily for 4 weeks.	Drug: K1 1000 µg; One pill daily for 4 weeks.; Other Names: Phylloquinone 1000 µg
Placebo Comparator: Placebo; Participants randomized to this arm will take 1 placebo pill daily for 4 weeks.	Other: Placebo; Placebo pill daily for 4 weeks.; Other Names: Sugar pill
Experimental: Vitamin K2 (MK-7) 300 µg; Participants randomized to this arm will take one Vitamin K2 (MK-7) 300 µg pill daily for 4 weeks.	Drug: Vitamin K2 (MK-7) 300 µg; One pill daily for 4 weeks.; Other Names: Menaquinone 300 µg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in uncarboxylated matrix Gla protein (ucMGP) levels	Plasma ucMGP levels will be measured from blood samples using an enzyme-linked immunoassay (ELISA).	Baseline, 4 weeks
Change in phylloquinone levels	Plasma phylloquinone will be measured using high-pressure liquid chromatography (HPLC).	Baseline, 4 weeks
Sufficient phylloquinone levels	Defined as the the proportion of participants achieving phylloquinone level of >1.0 nmol/L, which is the level achieved when adequate intakes are met.	Baseline, 4 weeks
Change in menaquinone-7 (MK-7) levels	Menaquinone-7 (MK-7) will be measured from blood samples using HPCL.	Baseline, 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study adherence	Adherence wil be assessed by analyzing pill counts for each participant.	4 weeks
Participant acceptability of intervention	Participants will use a 5 point LIkert scale to rate acceptability of the overall study, the pill tste, gastrointestinal tolerance, burden, and blood collection.	4 weeks

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Jean Liew, MD MS, Boston University Chobanian & Avedisian School of Medicine, Department of Rheumatology

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 21, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Vitamin K-1; Vitamin K-2; Menaquinone-7 (MK-7); Uncarboxylated matrix Gla protein (ucMGP); Phylloquinone
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Diterpenes; Quinones; Vitamin K; Naphthoquinones; Phytol; Vitamin K 1; Vitamin K 2; Sugars
• Other Study ID Numbers: H-44897; K23AR082938 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No