NCT01232647

Brief Summary

Vitamin K is thought to be important for bone health because it activates several proteins involved in bone formation. Poor dietary intake of vitamin K (mainly found in dark green leafy vegetables) is associated with bone loss and fractures. Giving supplements of the main dietary form of vitamin K (called K1) or another common form which our bodies make from K1(called MK4), to improve bone health have given mixed results. This confusion is thought to have arisen because these studies involved people who already had enough vitamin K or did not have osteoporosis. We want to test the hypothesis that treatment with bisphosphonates combined with vitamin K, in vitamin K deplete elderly women with osteoporosis, may offer additional benefit on skeletal metabolism and reduction of fracture risk. We want to test this by measuring vitamin K status in post-menopausal women with osteoporosis who are on the recommended treatment with a bisphosphonate and calcium/vitamin D supplements. Those with low vitamin K will then be recruited to study the effect of supplementation with either K1 or MK4.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
105

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Apr 2015

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 1, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 2, 2010

Completed
4.4 years until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2020

Completed
Last Updated

February 13, 2020

Status Verified

February 1, 2020

Enrollment Period

5 years

First QC Date

November 1, 2010

Last Update Submit

February 12, 2020

Conditions

Keywords

osteoporosisvitamin KBONE MINERAL DENSITYBIOCHEMICAL MARKERS OF BONE TURNOVER

Outcome Measures

Primary Outcomes (1)

  • Primary outcome measures- Changes in BMD at the Lumber spine, hip, fore-arm at 18 months.

    Measurement of changes in bone mineral density by DXA scan.

    18 months

Secondary Outcomes (1)

  • Secondary outcome measure- Bone Turnover as assessed by the biochemical markers (serum CTX, P1NP, BALP, carboxylated and undercarboxylated osteocalcin (OC), OPG). These markers will be measured at the same time point during each clinic visit.

    18 months

Study Arms (3)

Vitamin k1

ACTIVE COMPARATOR

1.0 mg of vitamin K1 (phylloquinone) and placebo MK4 will be given to one of the treatment arm for 18 months

Drug: Phylloquinone

placebo vitamin K1 and MK4

PLACEBO COMPARATOR

placebo pill of both vitamin K1 and MK4 given for 18 months to the control arm

Drug: placebo

Menatetrenone MK4

ACTIVE COMPARATOR

45 mg MK4 given daily and placebo vitamin K1 will be given to one of treatment arm for 18 months

Drug: Menatetrenone (MK4)

Interventions

1.0 mg daily of vitamin K1

Also known as: Vitamin K1
Vitamin k1

Menatetrenone (MK4) 45 mg daily

Also known as: Vitamin K2
Menatetrenone MK4

placebo vitamin K1 and placebo MK4 given daily for 18 months

Also known as: dummy pill
placebo vitamin K1 and MK4

Eligibility Criteria

Age55 Years - 85 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Informed consent to screening stage : assessment of vitamin K status
  • serum vitamin K concentration \< 0.35 ug/ml
  • \. ambulatory post-menopausal women aged between 55-85 years 2. Post-menopausal osteoporosis ( history of previous fragility fractures or BMD evidence of osteoporosis or osteopenia with at least one clinical risk factors such as low BMI, positive family history of osteoporosis) 3. Treatment with a bisphosphonate and calcium/vitamin D supplements for at least 12 months 4. Informed written consent 5. e GFR \>30 ml/min 6. normocalcaemia

You may not qualify if:

  • Age \<55 years, or \> 85 years
  • Male gender
  • severe renal impairment (CKD stage 4 and 5)
  • poor mobility (inability to walk 100 yards unaided)
  • malabsorption (extensive bowel surgery, short bowel)
  • generalised carcinomatosis
  • glucocorticoid therapy
  • inflammatory disorders (e.g. active rheumatoid arthritis, inflammatory bowel disease requiring oral glucocorticoids),
  • endocrine diseases (e.g. primary hyperparathyroidism, hyperthyroidism).
  • chronic liver disease
  • current treatment with teriparatide, strontium ranelate
  • Participation in a trial with an investigational product within the previous 3 months
  • Serum vitamin K \> 0.35 µg/ml
  • patients on anti-coagulants such as warfarin

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Guy's and St Thomas' Hospital NHS foundation Trust

London, SE1 7EH, United Kingdom

Location

Osteoporosis Unit, Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Related Publications (1)

  • Moore AE, Dulnoan D, Voong K, Ayis S, Mangelis A, Gorska R, Harrington DJ, Tang JCY, Fraser WD, Hampson G. The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial. Arch Osteoporos. 2023 Jun 20;18(1):83. doi: 10.1007/s11657-023-01288-w.

MeSH Terms

Conditions

Osteoporosis, PostmenopausalOsteoporosis

Interventions

Vitamin K 1menatetrenoneVitamin K 2

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Vitamin KNaphthoquinonesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPhytolDiterpenesTerpenesQuinonesPolycyclic Compounds

Study Officials

  • Geeta Hampson, MD

    Guy's and St Thomas' NHS Foundation Trust

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 2010

First Posted

November 2, 2010

Study Start

April 1, 2015

Primary Completion

March 31, 2020

Study Completion

March 31, 2020

Last Updated

February 13, 2020

Record last verified: 2020-02

Locations