Effects of Vitamin K on Lower-extremity Function in Adults With Osteoarthritis:

Effects of Vitamin K on Lower-extremity Function in Adults With Osteoarthritis: A Randomized Controlled Pilot Trial

The overall goal of this pilot randomized trial is to obtain necessary prerequisite data to conduct a randomized controlled intervention to test the effect of vitamin K supplementation on knee osteoarthritis progression and related functional decline. To address critical parameters required to design this larger RCT, we will conduct a double-blind, 2-armed, parallel-group intervention study, with a placebo run-in, in which 50 adults with mild to moderate knee OA and low baseline vitamin K status will be randomly assigned to 1 mg phylloquinone/day or matching placebo, and treated for 6 months. Specifically, we will: (1) compare the effects of 1 mg/day phylloquinone vs. placebo on the non-functional circulating form of MGP; (2) estimate rates of recruitment and retention, follow-up rates and reasons for loss to follow-up, response rates to questionnaires, adherence/compliance rates, and potential for site differences; and (3) determine the responsiveness of the Osteoarthritis Research Society International (OARSI)-recommended performance-based tests of physical function in adults with low vitamin K status and mild to moderate knee osteoarthritis. We will also obtain preliminary data on the distribution of MGP genotype at two clinical sites for effect size generation.

As of February 2025, based on attrition rate below what was initially expected, we revised our planned enrollment from 50 to 35, to achieve the original goal of 30 completers. This was approved by the study sponsor.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Dietary supplement: Vitamin K; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts University
    • Worcester, Massachusetts, United States, 01605
      • UMass Memorial Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 50 years
• Male or post-menopausal female (no menses in the last year)
• Plasma phylloquinone <1.0 nmol/L
• Chronic knee discomfort based on affirmative response to the question "During the past 12 months, have you had pain, aching, or stiffness in or around your knee(s) on most days for at least one month?"
• Kellgren-Lawrence (KL) grade 2-3 in at least one knee
• Ability to understand study procedures and to comply with them for the entire length of the study
• Ability to answer questions by phone
• Ability to swallow capsules

Exclusion Criteria:

• KL grade 4 in at least one knee
• Inability to walk
• Cognitive impairment (based on a Montreal Cognitive Assessment Test score ≤ 17)
• Widespread pain
• Malabsorption disorders (e.g. advance liver disease, stage 4 or 5 chronic renal disease, Crohn's disease, celiac sprue)
• Serious medical conditions or impairments that, in the view of the investigator, would obstruct study participation
• Plan to permanently relocate from the greater Boston, MA or Chapel Hill NC areas during the trial period
• Planned knee or hip arthroplasty during the study period
• Undergoing cancer treatment
• < 50 years old
• Circulating phylloquinone ≥ 1.0 nmol/L
• Warfarin (Jantoven) use
• Use of other investigational drugs
• Use of herbal, botanical or vitamin K supplements
• Use of assistive walking devices

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin K; Participants receive 1 mg/d phylloquinone orally for 24 weeks	Dietary supplement: Vitamin K; 1 mg/day phylloquinone (vitamin K1); Other Names: Phylloquinone
Placebo Comparator: Placebo; Participants receive daily placebo matching phylloquinone for 24 weeks	Dietary supplement: Placebo; Placebo capsule once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma uncarboxylated matrix gla protein	Plasma uncarboxylated matrix gla protein is considered a functional indicator of vitamin K status. We will evaluate how it changes in response to 1 mg/d vitamin K supplementation in adults with low vitamin K status at baseline and with radiographic knee OA.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma phylloquinone	Circulating phylloquinone is considered a global indicator of vitamin K status. We will evaluate how it changes in response to 1 mg/d vitamin K supplementation in adults with low vitamin K status at baseline and with radiographic knee OA.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower-extremity function - self reported	The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function index is a disease-specific, self-administered questionnaire, for assessing health status and health outcomes in osteoarthritis of the knee and/or hip. WOMAC function scores range from 0-68, with lower scores reflecting better function.	12 and 24 weeks
Lower-extremity function - objective measures	40-m fast gait speed, Chair stand test, Stair climb test, Timed-up-and-go test, 6 min walk test are measures of lower-extremity function recommended by the Osteoarthritis Research Society International to test physical performance in people with knee OA.	24 weeks
Knee pain	Knee pain, which is symptomatic of OA, will be evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Measurement of Intermittent and Constant Osteoarthritis Pain (ICOAP) self-reported questionnaires. WOMAC pain scores range from 0-20, with higher scores reflecting more pain. ICOAP scores range from 0-100, with higher scores reflecting more pain.	12 and 24 weeks

Collaborators and Investigators

• Sponsor: Tufts University
• Collaborators: University of North Carolina, Chapel Hill; Tufts Medical Center; University of Massachusetts, Worcester

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: osteoarthritis; nutrition; physical function
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Organic Chemicals; Substandard Drugs; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Terpenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Diterpenes; Quinones; Naphthoquinones; Phytol; Vitamin K; Vitamin K 1; Counterfeit Drugs
• Other Study ID Numbers: R21AR080297 (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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No