Clinical trial NCT00150969: Vitamin K Supplementation in Post-Menopausal Osteopenia
Official title: Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia (ECKO Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-Menopausal Osteoporosis
Post-Menopausal Osteopenia
Keywords: vitamin K
bone mineral density
post-menopausal women
randomized double blind placebo controlled trial
osteoporosis
women's health
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2005-09-08
Enrollment: 440
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.
timeFrame: 0 to 24 months
measure: Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.
timeFrame: 0 to 24 months
Secondary outcomes:
measure: Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.
timeFrame: 0 to 24 months
measure: Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.
timeFrame: 0 to 24 months
measure: Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker
timeFrame: 0-24 months
measure: Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX)
timeFrame: 0-24 months
measure: Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin
timeFrame: 0 to 24 months
measure: Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.
timeFrame: 0 to 48 months
measure: Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.
timeFrame: 0 to 48 months
measure: Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.
timeFrame: 0 to 48 months
measure: Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.
timeFrame: 0 to 48 months
measure: Difference in Serious Adverse Events
timeFrame: up to 48 months
measure: Difference in Number of New Cancers by Treatment Arm.
timeFrame: up to 48 months
measure: Difference in Number of New Clinical Fractures by Treatment Arm.
timeFrame: up to 48 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital Health Centre
state: Ontario
city: Toronto
country: Canada
facility: Mt. Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Osteoporosis Department
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook & Women's College Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: University Health Network, University of Toronto
name: Angela M Cheung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008 Oct 14;5(10):e196. doi: 10.1371/journal.pmed.0050196.