Vitamin K as Additive Treatment in Osteoporosis (VITKANDOP)
Recruitment status was Not yet recruiting
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.
Drug: Menaquinone (MK4)
|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|
- 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 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.
|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)|
Active Comparator: Vitamin k1
1.0 mg of vitamin K1 (phylloquinone) will be given to one of the treatment arm
1.0 mg daily for 18 months
Other Name: Vitamin K1
Placebo Comparator: placebo
placebo pill given for 18 months to the control arm
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01232647
|Contact: Geeta Hampson, MD||02071881284 ext firstname.lastname@example.org|
|Guy's and St Thomas' Hospital NHS foundation Trust||Not yet recruiting|
|London, United Kingdom, SE1 7EH|
|Principal Investigator: Geeta Hampson, MD|
|Study Director:||Ignac Fogelman, MD||King's College London|