Open-label Study to Evaluate the Effect of MBP-80 on Bone Remodelling

Study Overview
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Brief Summary
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This study will determine if daily oral intake of 200g of a marketed yogurt with fortified calcium content and a milk basic protein (MBP)80 mg benefits on bone cells activity in postmenopausal women. The efficacy of the product is measured by examining the variation of biochemical markers of bone turnover. MBP 80 is a particular protein contained in milk; it has been added to the yogurt provided for this study. The effects of MBP 80 on the quality of bone tissue have not yet been proven.

Detailed Description
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The morbidity and mortality associated with osteoporotic related fractures is devastating in terms of disability to an individual and cost to the global economy. As the world's population ages, this will present a major public health issue since a larger proportion of women remain undiagnosed and untreated even with the availability of therapies and calcium and vitamin D supplements. Consequently, it remains important to evaluate dairy products (milk, cheese, and yogurt) that can be safely provided as a supplement for bone health in addition to the current pharmacological treatments. The rationale of this study is to assess the beneficial effect of a daily dietary supplement of MBP 80 mg in a yogurt matrix with fortified calcium content on bone remodelling in healthy early postmenopausal women with neither osteoporosis nor estrogens/progestin therapy.

Official Title
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A 12-week, Open-label Study to Evaluate the Effect of MBP-80 (200g of Yogurt With Fortified Calcium Content and MBP 80 mg) on Bone Remodelling as Assessed by Bone Turnover Markers in Early Postmenopausal Women

Conditions
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Postmenopausal Osteoporosis

Intervention / Treatment
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* Dietary Supplement: 200 g yogurt with fortified calcium content and MBP 80 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Early postmenopausal women, aged 45-60 yrs old inclusive, with 1-5 yrs since last menses; naturally or surgically menopausal as a result of bilateral oophorectomy. Hysterectomized (≤ 5 yrs) women 50-60 yrs old. Lumbar Spine (L.S.;L1-L4) BMD > 0.772 g/cm2 (T-score of -2.5 on Hologic) and, Femoral Neck BMD > 0.572 g/cm2 (T-score of -2.5 on Hologic) and, Total Hip BMD > 0.637 g/cm2 (T-score of -2.5 on Hologic). Subjects must sign the Ethic Committee approved Informed Consent Form before any study procedure is initiated. Exclusion Criteria: Any intake of calcium and vitamin D supplements including multivitamins, nutritional or dietary supplements of any kind containing calcium and vit D within 3 months prior to screening visit 1A. Daily dietary calcium intake > 600 mg as assessed by the Calcium Intake Calculator (Appendix E). Subjects who already suffer from osteoporosis on the basis of a low BMD T-score ≤ - 2.5 at any site or a personal history of fragility fracture after age 40. Any past or present use of: Bisphosphonate PTH or PTH derivatives, eg. teriparatide Androgens, anabolic steroids or testosterone Tibolone Calcitriol Strontium ranelate Lithium, chronic warfarin or heparin use > 3 months, anticonvulsants (benzodiazepines are allowed), gonadotrophin-releasing hormone agonists, glitazones. Administration of any of the following treatments within the last 3 months prior to screening: Glucocorticosteroids (> 5 mg prednisone equivalent per day for > 10 days) Systemic hormone replacement therapy Selective estrogen receptor modulators (SERMs), eg, raloxifene Calcitonin Any unapproved hormone-like treatment in the opinion of the Principal Investigator (P.I.), i.e. phytoestrogens, isoflavones, etc. Antacids, H2 blockers, proton pump inhibitors for > 10 days Iron supplements for > 10 days Any condition or disease that may, according to the P.I., interfere with the evaluation of L.S. and Hip BMD; including but not limited to: advanced scoliosis or extensive lumbar fusion, less than 2 lumbar vertebrae (L1-L4) evaluable for DXA. Hyper or hypothyroidism: patients on stable dose of thyroid treatment with normal TSH will be allowed. Lab values for TSH must be normal or slightly abnormal, though clinically non significant in the opinion of the P.I. Current hyper or hypoparathyroidism, in the opinion of the P.I. Current hypocalcemia, in the opinion of the P.I. Vit D insufficiency (25-OH vitamin D level < 40 nmol/L) Significantly impaired renal function hereby defined as an estimated GFR ≤ 60 mL/min/ 1.73 m2 (4-variable MDRD equation). Rheumatoid arthritis. Paget's disease of bone. Any history of cancer within the past 5 years (except for basal cell carcinoma, dermal squamous cell carcinoma with 6 month remission and cervix carcinoma in situ). Any bone disease, i.e. osteomalacia or osteogenesis imperfecta. Chronic asthma, in the opinion of the P.I. Malabsorption syndrome (coeliac disease, inflammatory bowel disease, gastric bypass). Height, weight and girth which may preclude accurate DXA measurement; BMI outside ranges between 18.5 and 35 inclusive. Variation of more than 2 kg (gain or loss) within 2 months of the Screening. Presence of any vertebral fracture on the screening VFA (Vertebral Fracture Assessment) measured by DXA. Any previous or ongoing clinically significant illness that, in the opinion of the P.I., could prevent the patient from completing the study. Evidence of alcohol or substance abuse within the last 12 months that the P.I. believes would interfere with understanding or completing the study. Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures. Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: 200 g yogurt with fortified calcium content and MBP 80 mg|Intake of one container of vanilla or strawberry yogurt in the morning on a daily basis during 12 weeks.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median percent change in levels of serum β CTX (sCTX), a bone resorption marker. | The primary efficacy variable, the median percent change from baseline (Day 0) in levels of serum β-CTX (sCTX) at week 12, will be compared to the corresponding median percent change from day minus 28 (Day - 28) in levels of serum β-CTX (sCTX) at Day 0 for each participant. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median percent change in levels of P1NP, a bone formation marker. | A secondary efficacy variable, the median percent change from baseline (Day 0) in levels of serum P1NP (sP1NP) at week 12, will be compared to the corresponding median percent change from day minus 28 (Day - 28) in levels of serum P1NP(sP1NP) at Day 0 for each participant. | 12 weeks | 
| Median percent change in levels of serum β-CTX (sCTX), a bone resorption marker | A secondary efficacy variable, the median percent change from baseline (Day 0) in levels of serum β-CTX(sCTX) at week 4, will be compared to the corresponding median percent change from day minus 28 (Day - 28) in levels of serum β-CTX(sCTX) at Day 0 for each participant. | 4 weeks | 
| Median percent change in levels of urinary NTX(uNTX), a bone resorption marker. | A secondary efficacy variable, the median percent change from baseline (Day 0) in levels of urinary NTX(uNTX) at weeks 4 and 12, will be compared to the corresponding median percent change from day minus 28 (Day - 28) in levels of urinary NTX(uNTX) at Day 0 for each participant. | weeks 4 and 12 | 
| Median percent change in levels of serum osteocalcin (sOC), a bone formation marker. | A secondary efficacy variable, the median percent change from baseline (Day 0) in levels of serum osteocalcin(sOC) at week 12, will be compared to the corresponding median percent change from day minus 28 (Day - 28) in levels of serum osteocalcin(sOC) at Day 0 for each participant. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoporosis, postmenopausal women, bone remodelling, bone turnover markers