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

Study Overview
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Brief Summary
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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.

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

Conditions
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Osteo Arthritis Knee

Intervention / Treatment
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* Dietary Supplement: Vitamin K
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin K<br>Participants receive 1 mg/d phylloquinone orally for 24 weeks | Dietary Supplement: Vitamin K<br>* 1 mg/day phylloquinone (vitamin K1)<br>* Other names: Phylloquinone;|
| Placebo Comparator: Placebo<br>Participants receive daily placebo matching phylloquinone for 24 weeks | Dietary Supplement: Placebo<br>* Placebo capsule once daily<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, physical function, nutrition