Vitamin K for Osteoarthritis

Not currently recruiting at 2 trial locations

Overseen By Sarah Booth, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Tufts University

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether vitamin K can slow the progression of knee osteoarthritis and alleviate related physical decline. Participants will receive either a vitamin K supplement or a placebo for six months. The trial seeks adults over 50 with mild to moderate knee osteoarthritis and low blood levels of vitamin K. Eligible participants should have experienced knee pain, aching, or stiffness on most days for at least a month in the past year. As an unphased trial, this study provides a unique opportunity to contribute to understanding the potential benefits of vitamin K for knee osteoarthritis.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Vitamin K is generally safe. It is often used to help control blood clotting in people taking warfarin, a blood thinner, indicating that Vitamin K is well-tolerated.

Studies have explored its potential benefits for osteoarthritis, but specific information about side effects related to this condition remains limited. In other research areas, Vitamin K has shown promise in improving bone health and reducing pain, which is encouraging for its possible use in osteoarthritis.

This trial is in the "Not Applicable" phase, primarily aiming to collect initial data rather than prove safety or effectiveness. If Vitamin K were unsafe, it likely wouldn't be tested in this way. As always, discussing any concerns with a healthcare provider before joining a study is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Vitamin K for osteoarthritis because it represents a unique approach compared to standard treatments like NSAIDs or corticosteroids, which primarily target pain and inflammation. Vitamin K, specifically in the form of phylloquinone, is thought to play a role in bone and cartilage health, potentially addressing the underlying joint degeneration rather than just alleviating symptoms. This approach could lead to longer-term improvements in joint function and pain management, making it a promising avenue for those seeking alternatives to current osteoarthritis therapies.

What evidence suggests that vitamin K might be an effective treatment for knee osteoarthritis?

This trial will compare Vitamin K with a placebo to evaluate its effects on osteoarthritis. Research has shown that vitamin K might help manage osteoarthritis. One study found that vitamin K2 increased bone strength and cartilage thickness, which are important for healthy joints, and may help reduce pain from osteoarthritis. Another study suggested that vitamin K helps by reducing the hardening of tissues, which can worsen osteoarthritis. However, some studies did not find a significant effect of vitamin K on hand osteoarthritis, showing mixed results. Despite these mixed findings, the idea of using vitamin K remains strong because it supports bone and cartilage health. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• 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.

How Is the Trial Designed?

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+

University of Massachusetts, Worcester

Collaborator

Trials

372

Recruited

998,000+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Tufts Medical Center

Collaborator

Trials

264

Recruited

264,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Parenteral vitamin K1 (phytonadione) can cause severe adverse reactions resembling anaphylaxis, including hypotension, bradycardia, and even cardiac arrest, with an incidence of 3 per 10,000 doses when administered intravenously.

The reactions are likely due to a nonimmune-mediated anaphylactoid mechanism and can occur regardless of prior exposure to vitamin K1, highlighting the importance of caution even when precautions are taken.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing the Severe Reactions of Parenteral Vitamin K1. Britt, RB., Brown, JN.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06385275

The Role of Vitamin K on Knee Osteoarthritis Outcomes Participants randomized to this arm will take one Vitamin K2 (MK-7) 300 µg pill daily for 4 weeks. Intervention/Treatment, Drug : Vitamin K2 (MK-7) 300 µg.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5494092/

Vitamins K1 and K2: The Emerging Group ... - PubMed Central Using a small dose of vitamin K2 may benefit the patient by reducing the risk of osteoporosis, osteoarthritis, and vascular and tissue calcification.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2214031X25000543

Vitamins D and K jointly protect against osteoarthritis via ... Consistently, combined supplementation of vitamins D and K significantly alleviated cartilage degradation, while vitamin D or K alone could not (Fig. 4 F-H).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2584352/

Vitamin K in hand osteoarthritis: results from a randomised ... Despite a plausible biological rationale and a positive observational study, our trial results do not support a significant effect of vitamin K supplementation ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S075333222400581X

Vitamin K2 ameliorates osteoarthritis by suppressing ... VK2 can increase bone mass and cartilage thickness in the subchondral bone of the tibia, and reduce pain and the OARSI score induced by OA.

6. amjmed.com amjmed.com/article/s0002-9343(12)00881-9/fulltext

Vitamin K Deficiency Is Associated with Incident Knee ... Subclinical vitamin K deficiency is associated with increased risk of developing knee osteoarthritis and cartilage lesions, but not osteophytes.