Vitamin K Supplementation in Post-Menopausal Osteopenia

This study has been completed.
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00150969
First received: September 6, 2005
Last updated: November 19, 2012
Last verified: November 2012

September 6, 2005
November 19, 2012
January 2002
September 2006   (final data collection date for primary outcome measure)
  • Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
  • Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Changes in Bone Mineral Density at the spine (L1-L4) and the total hip.
Complete list of historical versions of study NCT00150969 on ClinicalTrials.gov Archive Site
  • Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
  • Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
  • Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    measured by osteocalcin on elecsys platform
  • Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX) [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    measured by CTX Elisa assay on elecsys platform
  • Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    measured by osteocalcin hydroxyapatite binding assay
  • Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
  • Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
  • Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
  • Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
  • Difference in Serious Adverse Events [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
    These include hospitalizations for pneumonia, heart failure, gastro-intestinal bleeding, elective and non-elective surgery, cancer and death.
  • Difference in Number of New Cancers by Treatment Arm. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
  • Difference in Number of New Clinical Fractures by Treatment Arm. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
    these included fragility fractures
  • 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.
Not Provided
Not Provided
 
Vitamin K Supplementation in Post-Menopausal Osteopenia
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Post-Menopausal Osteoporosis
  • Post-Menopausal Osteopenia
  • Dietary Supplement: vitamin K1 (phylloquinone)
  • Dietary Supplement: placebo
    1 pill daily
  • Experimental: phyloquinone
    5 mg Vitamin K1
    Intervention: Dietary Supplement: vitamin K1 (phylloquinone)
  • Placebo Comparator: placebo
    Intervention: Dietary Supplement: placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
440
September 2007
September 2006   (final data collection date for primary outcome measure)

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.
Female
Not Provided
Yes
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00150969
CIHR-50422
Yes
Not Provided
University Health Network, Toronto
Canadian Institutes of Health Research (CIHR)
Principal Investigator: Angela M Cheung, MD, PhD University Health Network, University of Toronto
University Health Network, Toronto
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP