Official Title: “Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia (ECKO Trial)”

The purpose of this study is to determine whether supplementation with 5 mg vitamin K daily over a 2-year period will prevent bone loss in post-menopausal women with osteopenia.

Study Type: Interventional

Study Design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Osteoporosis is major cause of morbidity and mortality in Canadian postmenopausal women. It is a systemic disease characterized by low bone mass and deterioration of bone microarchitecture, resulting in bone fragility and an increased risk of fractures. One in six women over the age of 50 have osteoporosis. The lifetime risk of an osteoporotic fracture for an average 50 year-old Canadian woman is >40%. The annual health care costs for osteoporotic fractures in Canada have been estimated to exceed $1.3 billion.

Recent data suggest that vitamin K supplements may decrease bone loss and prevent fractures.

Vitamin K is a co-factor of gamma-glutamyl carboxylase, an enzyme that catalyzes the gamma-carboxylation of glutamic acid residues in bone matrix proteins such as osteocalcin.

Vitamin K has been reported to enhance bone formation in both in vitro studies and in vivo studies in animals. Vitamin K levels are low in individuals with osteoporosis and in patients with osteoporotic fractures. The few studies examining vitamin K supplementation in humans have showed promising results with no significant side effects, but these studies had significant methodological shortcomings such as inadequate sample size and lack of randomization.

The primary objective of our study is to examine whether vitamin K supplementation will increase bone mineral density in postmenopausal women with osteopenia. Our secondary objectives are to examine the possible adverse effects from long-term vitamin K supplementation, to investigate whether vitamin K will decrease risk of fractures and to determine if vitamin K affects quality of life. Our hypotheses are that vitamin K increases bone mineral density in postmenopausal women, and that there are no significant adverse effects from vitamin K supplementation.

Intervention(s) in this Clinical Trial

• Drug: vitamin K1 (phylloquinone)

Primary Measures

• Changes in Bone Mineral Density at the spine (L1-L4) and the total hip.

Secondary Measures

• 1. The potential adverse effects from long-term vitamin K1 supplementation.
• 2. Whether vitamin K1 supplementation affects levels of bone formation markers and bone resorption markers.
• 3. Whether vitamin K1 supplementation affects the degree of carboxylation of OC, a major vitamin K-dependent protein in bone.
• 4. Whether vitamin K1 supplementation affects health-related quality of life.
• 5. Whether vitamin K1 supplementation decreases the risk of having fragility fractures.
• 6. Whether ApoE modulates the effect of vitamin K on bone.

Inclusion Criteria:

• Postmenopausal: One year since the natural cessation of menses, or Hysterectomy with either postmenopausal status confirmed by FSH lab values, or age 55 and above AND 2. Osteopenic:
• T-score at baseline has to be between (and including) -1.0 and
• 2.0 in the lumbar spine (L1-L4), total hip or femoral neck, and the lowest reading of the above three measurements must be between -1.0 and
• 2.0

Exclusion Criteria:

• 1. Women ever having had a fragility fracture after age 40;
• 2. Women currently on anticoagulants, previously on anticoagulants in the past 3 months, or expected to be on anticoagulants in the near future;
• 3. Women on hormone replacement therapy, raloxifene, bisphosphonates or calcitonin during the past 3 months;
• 4. Women who have ever been on a bisphosphonate for more than 6 months;
• 5. Women previously diagnosed with Paget's disease, hyperparathyroidism, hyperthyroidism or other metabolic bone diseases;
• 6. Women with decompensated diseases of the liver, kidney, pancreas, lung, or heart;
• 7. Women with a history of active cancer in the past 5 years;
• 8. Women taking mega-doses of vitamin A (more than 10,000 iu per day) or E (more than 400 iu per day);
• 9. Women involved in other clinical trials;
• 10. Any women who, in the opinion of the principal investigator, is at poor medical or psychiatric risk for the study.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University Health Network, Toronto

Overall Clinical Trial Officials and Contacts

Angela M Cheung, MD, PhD Principal Investigator University Health Network, University of Toronto  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00150969

Study ID Number: CIHR-50422

ClinicalTrials.gov Identifier: NCT00150969

Health Authority: Canada: Health Canada