Vitamin K Supplementation in Post-Menopausal Osteopenia

• ClinicalTrials.gov Identifier: NCT00150969
• Recruitment Status: Completed
• First Posted: September 8, 2005
• Results First Posted: March 26, 2012
• Last Update Posted: November 22, 2012
• Sponsor: University Health Network, Toronto
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by: University Health Network, Toronto

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Post-Menopausal Osteoporosis; Post-Menopausal Osteopenia	Dietary Supplement: vitamin K1 (phylloquinone); Dietary Supplement: placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 440 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia (ECKO Trial)
• Study Start Date: January 2002
• Actual Primary Completion Date: September 2006
• Actual Study Completion Date: September 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: phyloquinone; 5 mg Vitamin K1	Dietary Supplement: vitamin K1 (phylloquinone)
Placebo Comparator: placebo	Dietary Supplement: placebo; 1 pill daily

Outcome Measures

Primary Outcome Measures :

1. Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms. [ Time Frame: 0 to 24 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
2. Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms. [ Time Frame: 0 to 24 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Secondary Outcome Measures :

1. Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms. [ Time Frame: 0 to 24 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
2. Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms. [ Time Frame: 0 to 24 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
3. Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker [ Time Frame: 0-24 months ]
   measured by osteocalcin on elecsys platform
4. Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX) [ Time Frame: 0-24 months ]
   measured by CTX Elisa assay on elecsys platform
5. Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin [ Time Frame: 0 to 24 months ]
   measured by osteocalcin hydroxyapatite binding assay
6. Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms. [ Time Frame: 0 to 48 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
7. Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms. [ Time Frame: 0 to 48 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
8. Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms. [ Time Frame: 0 to 48 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
9. Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms. [ Time Frame: 0 to 48 months ]
   BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
10. Difference in Serious Adverse Events [ Time Frame: up to 48 months ]
    These include hospitalizations for pneumonia, heart failure, gastro-intestinal bleeding, elective and non-elective surgery, cancer and death.
11. Difference in Number of New Cancers by Treatment Arm. [ Time Frame: up to 48 months ]
12. Difference in Number of New Clinical Fractures by Treatment Arm. [ Time Frame: up to 48 months ]
    these included fragility fractures

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Canada, Ontario

St. Michael's Hospital Health Centre

Toronto, Ontario, Canada, M5C 2T2

Mt. Sinai Hospital

Toronto, Ontario, Canada, M5G 1X5

University Health Network, Osteoporosis Department

Toronto, Ontario, Canada, M5G 2C4

Sunnybrook & Women's College Health Sciences Centre

Toronto, Ontario, Canada, M5S 1B2

University of Toronto

Toronto, Ontario, Canada, M5S 3E2

Sponsors and Collaborators

University Health Network, Toronto

Canadian Institutes of Health Research (CIHR)

Investigators

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

More Information

Publications of Results:

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. Erratum in: PLoS Med. 2008 Dec;5(12):e247.

• ClinicalTrials.gov Identifier: NCT00150969
• Other Study ID Numbers: CIHR-50422
• First Posted: September 8, 2005
• Results First Posted: March 26, 2012
• Last Update Posted: November 22, 2012
• Last Verified: November 2012

Keywords provided by University Health Network, Toronto:

vitamin K; bone mineral density; post-menopausal women; randomized double blind placebo controlled trial; osteoporosis; women's health

Additional relevant MeSH terms:

Osteoporosis; Bone Diseases, Metabolic; Osteoporosis, Postmenopausal; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Vitamin K; Vitamin K 1; Vitamins; Micronutrients; Physiological Effects of Drugs; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants