Vitamin K Supplementation in Post-Menopausal Osteopenia - Full Text View

Sponsor:	University Health Network, Toronto
Collaborator:	Canadian Institutes of Health Research (CIHR)
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00150969

Purpose

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	Intervention	Phase
Post-Menopausal Osteoporosis Post-Menopausal Osteopenia	Dietary Supplement: vitamin K1 (phylloquinone) Dietary Supplement: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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)

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Menopause Minerals Osteoporosis Vitamin K

Drug Information available for: Vitamin K1 Vitamin K Phytonadione

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

Changes in Bone Mineral Density at the spine (L1-L4) and the total hip. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
measured on same scanner at UHN using DEXA Hologic

Secondary Outcome Measures:

1. The potential adverse effects from long-term vitamin K1 supplementation. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
2. Whether vitamin K1 supplementation affects levels of bone formation markers and bone resorption markers. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
measured by osteocalcin on elecsys platform
3. Whether vitamin K1 supplementation affects the degree of carboxylation of OC, a major vitamin K-dependent protein in bone. [ Time Frame: up to 48 months ] [ Designated as safety issue: No ]
measured by osteocalcin hydroxyapatite binding assay
4. Whether vitamin K1 supplementation affects health-related quality of life. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
using SF36 data
5. Whether vitamin K1 supplementation decreases the risk of having fragility fractures. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
data on fragility fractured collected every 6 months. Events leading to fracture evaluated by OP specialist. X-ray of fracture obtained.
6. Whether ApoE modulates the effect of vitamin K on bone. [ Time Frame: up to 48 months ] [ Designated as safety issue: No ]
genetic variant of ApoE identified in all study participants at baseline.

Enrollment:	453
Study Start Date:	January 2002
Study Completion Date:	September 2007
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: phyloquinone 5 mg Vitamin K1	Dietary Supplement: vitamin K1 (phylloquinone)
Placebo Comparator: placebo	Dietary Supplement: placebo 1 pill daily

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

Genders 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:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00150969

Locations

Canada, Ontario
University Health Network, Osteoporosis Department
Toronto, Ontario, Canada, M5G 2C4
St. Michael's Hospital Health Centre
Toronto, Ontario, Canada, M5C 2T2
Sunnybrook & Women's College Health Sciences Centre
Toronto, Ontario, Canada, M5S 1B2
Mt. Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
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:

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.

ClinicalTrials.gov Identifier:	NCT00150969 History of Changes
Other Study ID Numbers:	CIHR-50422
Study First Received:	September 6, 2005
Last Updated:	June 11, 2010
Health Authority:	Canada: Health Canada

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:

Bone Diseases, Metabolic
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases
Musculoskeletal Diseases
Vitamin K 1
Vitamin K
Vitamins
Micronutrients
Growth Substances

Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012