Post-Menopausal OsteoporosisPhase 3NCT00150969
Vitamin K Supplementation in Post-Menopausal Osteopenia
A Phase 3 study testing vitamin K1 (phylloquinone) in people with Post-Menopausal Osteoporosis and Post-Menopausal Osteopenia, run by University Health Network, Toronto at 5 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Post-Menopausal Osteoporosis, Post-Menopausal Osteopenia
- What is being tested?
- vitamin K1 (phylloquinone)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 440 participants
- Where
- 5 sitesCanada
- Study dates
- Jan 2002to Sep 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
St. Michael's Hospital Health Centre
Toronto, Ontario, M5C 2T2
Mt. Sinai Hospital
Toronto, Ontario, M5G 1X5
University Health Network, Osteoporosis Department
Toronto, Ontario, M5G 2C4
Sunnybrook & Women's College Health Sciences Centre
Toronto, Ontario, M5S 1B2
University of Toronto
Toronto, Ontario, M5S 3E2
About this study
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.
Read the 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.
- Being tested
- vitamin K1 (phylloquinone), placebo
- Keywords
- vitamin K, bone mineral density, post-menopausal women, randomized double blind placebo controlled trial, osteoporosis, women's health
- Medical subject headings
- Osteoporosis, Postmenopausal, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vitamin K1 (phylloquinone)Dietary supplement
placeboDietary supplement
1 pill daily
| Study group | Role | What they receive |
|---|---|---|
| phyloquinone | Experimental | 5 mg Vitamin K1 Receives: Dietary Supplement: vitamin K1 (phylloquinone) |
| placebo | Placebo comparator | Not described Receives: Dietary Supplement: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 24 months
Secondary outcomes (12)
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 24 months
Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker
measured by osteocalcin on elecsys platform
Measured: 0-24 months
Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX)
measured by CTX Elisa assay on elecsys platform
Measured: 0-24 months
Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin
measured by osteocalcin hydroxyapatite binding assay
Measured: 0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.
BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer
Measured: 0 to 48 months
Difference in Serious Adverse Events
These include hospitalizations for pneumonia, heart failure, gastro-intestinal bleeding, elective and non-elective surgery, cancer and death.
Measured: up to 48 months
Difference in Number of New Cancers by Treatment Arm.
Measured: up to 48 months
Difference in Number of New Clinical Fractures by Treatment Arm.
these included fragility fractures
Measured: up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2005 (estimated)
- Study startJan 2002
- Primary completionSep 2006
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-Menopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 440 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Angela M Cheung, MD, PhD, Principal investigator, University Health Network, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00150969
- Sponsor's protocol ID
- 01-0169
- Other IDs
- 50422
- Status last verified
- Dec 2023
- First submitted
- 6 Sep 2005
- Last updated
- 28 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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. doi: 10.1371/journal.pmed.0050196.
PubMed 18922041
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia (ECKO Trial)
- ClinicalTrials.gov ID
- NCT00150969
- Acronym / sponsor ID
- 01-0169
- Keywords
- vitamin K, bone mineral density, post-menopausal women, randomized double blind placebo controlled trial, osteoporosis, women's health
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 440 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Jan 2002
- Primary completion
- Sep 2006 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 8 Sep 2005 (estimated)
- Results
- Posted 26 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| phyloquinone | Experimental | Dietary Supplement: vitamin K1 (phylloquinone)5 mg Vitamin K1 |
| placebo | Placebo comparator | Dietary Supplement: placebo |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vitamin K1 (phylloquinone) | Dietary supplement | phyloquinone |
| placebo1 pill daily | Dietary supplement | placebo |
Primary outcome
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
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
12 secondary outcomes
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.
Time frame: 0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.
Time frame: 0 to 24 months
Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker
Time frame: 0-24 months
Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX)
Time frame: 0-24 months
Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin
Time frame: 0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.
Time frame: 0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.
Time frame: 0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.
Time frame: 0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.
Time frame: 0 to 48 months
Difference in Serious Adverse Events
Time frame: up to 48 months
Difference in Number of New Cancers by Treatment Arm.
Time frame: up to 48 months
Difference in Number of New Clinical Fractures by Treatment Arm.
Time frame: up to 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 18922041Cheung 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela M Cheung, MD, PhD principal investigator
University Health Network, University of Toronto
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing vitamin K1 (phylloquinone) in people with Post-Menopausal Osteoporosis and Post-Menopausal Osteopenia, run by University Health Network, Toronto at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00150969, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2023.