Vitamin K as Additive Treatment in Osteoporosis (VITKANDOP)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by Guy's and St Thomas' NHS Foundation Trust.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01232647
First received: November 1, 2010
Last updated: NA
Last verified: October 2010
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Post-Menopausal Osteoporosis
Drug: Phylloquinone
Drug: Menaquinone (MK4)
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Additive Effect of Vitamin K Supplementation and Bisphosphonate on Fracture Risk in Post-menopausal Osteoporosis

Resource links provided by NLM:


Further study details as provided by Guy's and St Thomas' NHS Foundation Trust:

Primary Outcome Measures:
  • Primary outcome measures- Changes in BMD at the Lumber spine, hip, fore-arm at 18 months. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Measurement of changes in bone mineral density by DXA scan.


Secondary Outcome Measures:
  • 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. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Laboratory analyses of serum and/or plasma at baseline, 3, 6, 12 and 18 months.


Estimated Enrollment: 150
Study Start Date: April 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vitamin k1
1.0 mg of vitamin K1 (phylloquinone) will be given to one of the treatment arm
Drug: Phylloquinone
1.0 mg daily for 18 months
Other Name: Vitamin K1
Placebo Comparator: placebo
placebo pill given for 18 months to the control arm
Drug: placebo
placebo given daily for 18 months
Other Name: dummy pill
Active Comparator: Menaquinone MK4
MK4 given daily to one of treatment arm 45 mg daily for 18 months
Drug: Menaquinone (MK4)
MK4 45 mg daily for 18 months
Other Name: Vitamin K2

Detailed Description:

Vitamin K is important for skeletal health. Vitamin K is essential for the carboxylation of several Gla proteins in bone which are implicated in bone formation and mineralization. These include osteocalcin (OC) and matrix Gla protein (MGP). Carboxylation of the glutamic acid residues of these proteins optimises their function. Vitamin K occurs as either phylloquinone (vitamin K1) which is the major dietary form or menaquinones (MKs or vitamin K2) which are mainly of bacterial origin. MK4 of the vitamin K2 series has additional, carboxylation-independent, functions including the regulation of osteoblastic specific markers such as alkaline phosphatase (BALP), and osteoprotegerin (OPG) and has inhibitory effects on osteoclast activity. Several observational studies have shown that low vitamin K status is associated with low bone mineral density (BMD) and increased fracture risk, although proof of causality is lacking. The results of several placebo-controlled clinical trials of vitamin K1 and MK4 have been conflicting with some, but not all, showing a positive effect of vitamin K1 on BMD or bone turnover. Positive fracture efficacy has been demonstrated with high-dose MK4, although most trials were on Japanese women. These intervention studies may have been hampered by the study design such as inclusion of vitamin K replete subjects or healthy non-osteoporotic women. The use of vitamin K in the prevention of bone loss and/or fractures in high-risk post-menopausal women with osteoporosis who are vitamin K deplete merits further investigations. The prevalence of low vitamin K stores is high in elderly subjects with osteoporosis. Preliminary data in Japanese women suggest that combined treatment with a bisphosphonate and vitamin K, at least vitamin K2 (MK4), appears to have an additive beneficial effect on BMD and bone resorption. There have been no such studies in a caucasian osteoporotic population. 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.

The first part will be a cross-sectional study of post-menopausal women with osteoporosis aged between 60-80 years who are on treatment with bisphosphonate. Their vitamin K status will be determined and those patients who are found to have low vitamin K concentrations defined as <0.15 ug/ml will be invited to take part in an 18 months prospective randomised placebo controlled trial.

Eligible patients will be randomised to 3 arms (50 patients in each arm). All 3 groups will continue to receive weekly oral bisphosphonate (commonly Alendronate 70 mg weekly) and adjunctive calcium/vitamin D supplements (1.0g of calcium and 800 I.U of cholecalciferol). The control arm (Group A) will receive placebo. Group B will receive 1.0mg daily of vitamin K1 and MK4 placebo. Group C will receive vitamin K2 (MK4) 45 mg daily and vitamin K1 placebo. Patients will be seen at baseline and at 3, 6, 12 and 18 months. Changes in BMD at the lumbar spine, hip, fore-arm at 18 months and the biochemical parameters at each time point will be compared between the groups.

  Eligibility

Ages Eligible for Study:   55 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion in the cross-sectional part of the study which involves assessment of vitamin K status

  1. Informed consent to screening stage : assessment of vitamin K status
  2. serum vitamin K concentration < 0.15 ug/ml

Inclusion into the randomised controlled trial

1. 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

  • Exclusion Criteria:

    1. Age <55 years, or > 85 years
    2. Male gender
    3. severe renal impairment (CKD stage 4 and 5)
    4. poor mobility (inability to walk 100 yards unaided)
    5. malabsorption (extensive bowel surgery, short bowel)
    6. generalised carcinomatosis
    7. glucocorticoid therapy
    8. inflammatory disorders (e.g. active rheumatoid arthritis, inflammatory bowel disease requiring oral glucocorticoids),
    9. endocrine diseases (e.g. primary hyperparathyroidism, hyperthyroidism).
    10. chronic liver disease
    11. current treatment with teriparatide, strontium ranelate
    12. Participation in a trial with an investigational product within the previous 3 months
    13. Serum vitamin K > 0.15 µg/ml
    14. patients on anti-coagulants such as warfarin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01232647

Contacts
Contact: Geeta Hampson, MD 02071881284 ext 81284 geeta.hampson@kcl.ac.uk

Locations
United Kingdom
Guy's and St Thomas' Hospital NHS foundation Trust Not yet recruiting
London, United Kingdom, SE1 7EH
Principal Investigator: Geeta Hampson, MD         
Sponsors and Collaborators
Guy's and St Thomas' NHS Foundation Trust
Investigators
Study Director: Ignac Fogelman, MD King's College London
  More Information

No publications provided

Responsible Party: Dr Geeta Hampson, Guy's and St Thomas' Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01232647     History of Changes
Other Study ID Numbers: Eudract number - 2010-02258712
Study First Received: November 1, 2010
Last Updated: November 1, 2010
Health Authority: United Kingdom : Medicine and Healthcare Products Regulatory agency

Keywords provided by Guy's and St Thomas' NHS Foundation Trust:
osteoporosis
vitamin K
BONE MINERAL DENSITY
BIOCHEMICAL MARKERS OF BONE TURNOVER

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Vitamin K 1
Vitamin K
Vitamins
Vitamin K 2
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 July 28, 2014