Vitamin K for Osteoarthritis

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Tufts University

Must not be taking: Warfarin, Investigational drugs, Vitamin K

Disqualifiers: KL grade 4, Cognitive impairment, Malabsorption, Cancer treatment, others

Trial Summary

What is the purpose of this 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.

Will I have to stop taking my current medications?

The trial requires that you stop using warfarin (a blood thinner), any investigational drugs, and herbal, botanical, or vitamin K supplements before participating.

What data supports the effectiveness of the drug Vitamin K for osteoarthritis?

Research suggests that Vitamin K, particularly Vitamin K2, is beneficial for bone health and may help prevent bone fractures, which is relevant for osteoarthritis patients. Although direct evidence for osteoarthritis is limited, Vitamin K's role in bone metabolism and its potential to reduce fracture risk could indirectly support its use in managing osteoarthritis symptoms. ^{1 2 3 4 5}

Is Vitamin K safe for humans?

Vitamin K1, especially when given by injection, can cause severe allergic reactions in some people, including breathing problems and heart issues. These reactions are rare but can be serious, so it's important to be cautious with its use. ^{6 7 8 9 10}

How does the drug Vitamin K differ from other treatments for osteoarthritis?

Vitamin K is unique because it may help improve bone health by supporting the function of osteocalcin, a protein important for bone strength, and potentially reducing bone loss, which is not a focus of most osteoarthritis treatments. Unlike typical pain relief medications for osteoarthritis, Vitamin K works by influencing bone metabolism and may have additional benefits for bone density. ^{1 2 3 4 11}

Research Team

Eligibility Criteria

Adults over 50 with mild to moderate knee osteoarthritis and low vitamin K levels can join this study. Participants must be able to swallow capsules, have no severe cognitive impairments or serious medical conditions that would interfere with the trial, not use walking aids or certain supplements, and not plan major relocations or surgeries during the study.

Inclusion Criteria

I can answer questions over the phone.

I have moderate knee arthritis.

I am a man or a woman who has not had a menstrual cycle in the last year.

Exclusion Criteria

Cognitive impairment (based on a Montreal Cognitive Assessment Test score ≤ 17)

Use of other investigational drugs

I am scheduled for knee or hip replacement surgery.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Placebo Run-in

Participants undergo a placebo run-in phase before randomization

2 weeks

Treatment

Participants receive 1 mg/d phylloquinone or placebo for 24 weeks

24 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Behavioural Intervention)
• Vitamin K (Vitamin K)

Trial Overview The trial is testing if taking 1 mg of Vitamin K daily for six months can slow down knee osteoarthritis progression compared to a placebo. It's a double-blind study where neither participants nor researchers know who gets Vitamin K or placebo until after the results are collected.

Participant Groups

Group I: Vitamin K Experimental Treatment 1 Intervention

Participants receive 1 mg/d phylloquinone orally for 24 weeks

Group II: Placebo Placebo Group 1 Intervention

Participants receive daily placebo matching phylloquinone for 24 weeks

Who Is Running the Clinical Trial?

Tufts University

Lead Sponsor

Trials

271

Recruited

595,000+

Susan Pandya

Tufts University

Chief Medical Officer

MD from Tufts University School of Medicine

Kenneth Getz

Tufts University

Chief Executive Officer since 2021

MBA from the J.L. Kellogg Graduate School of Management at Northwestern University, BA from Brandeis University

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Dr. Peggy P. McNaull

University of North Carolina, Chapel Hill

Chief Medical Officer

MD from Louisiana State University School of Medicine

Dr. Lynne Fiscus

University of North Carolina, Chapel Hill

Chief Executive Officer since 2020

MD from Georgetown University, MPH from UNC

Tufts Medical Center

Collaborator

Trials

264

Recruited

264,000+

Michael Dandorph

Tufts Medical Center

Chief Executive Officer since 2022

MBA

Helen Boucher

Tufts Medical Center

Chief Medical Officer since 2022

MD, FACP, FIDSA

Findings from Research

In a study of 259 patients with knee osteoarthritis followed for 2 years, higher dietary vitamin K intake was linked to significant improvements in knee symptoms, as measured by the WOMAC scores.

While vitamin K intake showed promise in reducing symptoms, its effect on knee structures, such as cartilage defects, remains unclear, indicating a need for further clinical trials on vitamin K supplementation for knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations Between Dietary Intake of Vitamin K and Changes in Symptomatic and Structural Changes in Patients With Knee Osteoarthritis. Liao, Z., Chang, J., Zhu, Z., et al.[2023]

Vitamin K is essential for the carboxylation of proteins like osteocalcin, which is important for bone health, and low intake of vitamin K is linked to a higher risk of osteoporotic fractures.

High doses of vitamin K2 (menatetrenone) have been shown to effectively prevent bone mineral loss and reduce fracture risk in osteoporotic patients, while the benefits of vitamin K1 on bone health remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of vitamin K on calcium and bone metabolism. Zittermann, A.[2022]

Dietary intake of vitamin K (phylloquinone) below 100 micrograms daily may not be sufficient for optimal bone health, potentially increasing the risk of osteoporosis and fractures due to undercarboxylation of osteocalcin.

Family physicians should promote adequate vitamin K intake, especially in elderly populations, to help prevent bone loss and fractures, highlighting the need for further research on vitamin K's role in bone metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone health. New role for vitamin K? Ryan-Harshman, M., Aldoori, W.[2018]

Phylloquinone (vitamin K1) and menaquinones (vitamin K2) have different metabolic pathways and transport mechanisms, with phylloquinone primarily transported by triglyceride-rich lipoproteins and menaquinones by low-density lipoproteins, affecting their uptake in tissues like bones.

Menaquinone-4 (MK-4) has shown specific clinical benefits at pharmacological doses for conditions like osteoporosis and cancer, and it activates a unique signaling pathway, suggesting potential therapeutic roles beyond its traditional functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism and cell biology of vitamin K. Shearer, MJ., Newman, P.[2022]

Vitamin K2 has been approved in Japan since 1995 for treating osteoporosis, effectively reducing new bone fractures and maintaining bone mineral density (BMD).

A systematic review of seven Japanese trials indicates that Vitamin K2, especially menaquinone-4, is linked to increased BMD and lower fracture rates, but further large-scale randomized controlled trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vitamin K2]. Ishida, Y.[2018]

Vitamin K1 can cause various cutaneous reactions, including localized eczematous plaques and morphea-form patches, with the eczematous type appearing at the injection site within an average of 13 days and sometimes persisting for over 18 months despite treatment.

The study highlights that adverse reactions to Vitamin K1 are often overlooked due to their low incidence and variable presentation, emphasizing the need for awareness among clinicians to ensure proper diagnosis and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous reactions associated with vitamin K1. Wilkins, K., DeKoven, J., Assaad, D.[2007]

In a study of 105 patients on warfarin, intravenous phytonadione (vitamin K1) was found to be safe, with only 1.9% experiencing mild adverse reactions during infusion, indicating a low risk profile for this intervention.

Phytonadione effectively corrected anticoagulation before procedures without increasing the risk of thromboembolism, and it did not delay the resumption of therapeutic anticoagulation after surgery, with a median return time of 4.1 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy. Shields, RC., McBane, RD., Kuiper, JD., et al.[2019]

Oral vitamin K(1) can be used to prevent late vitamin K deficiency bleeding (VKDB) in neonates when injectable forms are unavailable, but it is less effective than intramuscular vitamin K, which is preferred for its superior efficacy.

For exclusively breast-fed neonates, multiple oral doses are necessary for effective late VKDB prevention, with suggested regimens including 1 mg at birth followed by 25 μg daily for 13 weeks or 2 mg at birth followed by 1 mg weekly for 3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of oral vitamin K for prevention of late vitamin k deficiency bleeding in neonates when injectable vitamin K is not available. Ipema, HJ.[2012]

In a study of 81 outpatients with an INR greater than 5.0, oral vitamin K1 effectively lowered INR levels to below 5.0 in 96% of cases without causing resistance to further anticoagulation.

The combination of withholding warfarin doses and administering 2.5 mg of oral vitamin K1 is a safe, reliable, and cost-effective method for correcting excessive anticoagulation in patients without significant bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction of excessive anticoagulation with low-dose oral vitamin K1. Weibert, RT., Le, DT., Kayser, SR., et al.[2019]

In a 3-year randomized, double-blind, placebo-controlled study involving 181 postmenopausal women, vitamin K1 supplementation (1 mg/day) combined with minerals and vitamin D significantly reduced bone loss at the femoral neck compared to placebo and the mineral + vitamin D group.

The study found a 1.7% reduction in bone loss at the femoral neck for the vitamin K1 group compared to placebo, suggesting that vitamin K1 may play an important role in maintaining bone health in postmenopausal women when taken alongside other supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Braam, LA., Knapen, MH., Geusens, P., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Associations Between Dietary Intake of Vitamin K and Changes in Symptomatic and Structural Changes in Patients With Knee Osteoarthritis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effects of vitamin K on calcium and bone metabolism. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Bone health. New role for vitamin K? [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Metabolism and cell biology of vitamin K. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[Vitamin K2]. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Cutaneous reactions associated with vitamin K1. [2007]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Characterizing the Severe Reactions of Parenteral Vitamin K1. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Use of oral vitamin K for prevention of late vitamin k deficiency bleeding in neonates when injectable vitamin K is not available. [2012]

10. United States pubmed.ncbi.nlm.nih.gov

Correction of excessive anticoagulation with low-dose oral vitamin K1. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. [2019]