Design and Development of a Novel Food Supplement for Osteoporosis Based on Gut Microbiome Mechanisms

Study Overview
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Brief Summary
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It is well proven that the intestinal microbe regulates bone metabolism by the absorption of calcium and other metallic trace elements. Studies also show that regulation of the intestine and its microbe can affect bone density and resistance to a variety of animal models and humans. At the same time, interest in polyphenol-intestinal microbial interactions and in particular flavonoids and catechins has increased. Indeed, it has been observed that they are transformed via the microbe into bioactive compounds, and polyphenols themselves can modify the synthesis of the intestinal microbe. OSTEOME aspires to design and develop a novel dietary supplement for osteoporosis, activating the intestinal microbiome. At the same time companion biomarkers will be studied related to the efficacy and tolerability of the new supplement. The selection of flavonoids will take place through in vitro and in silico studies focusing on their interaction with pathways that regulate the activity of osteoclasts and osteoblasts. The efficacy and tolerability of the dietary supplement will be evaluated through a randomized clinical intervention.

Official Title
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Design and Development of a Novel Food Supplement for Osteoporosis Based on Gut Microbiome Mechanisms: Efficacy and Tolerability Assessment

Conditions
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Osteopenia, Postmenopausal Osteopenia

Intervention / Treatment
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* Dietary Supplement: Calcium and vitamin D supplement
* Dietary Supplement: Calcium, vitamin D and prebiotic supplement
* Dietary Supplement: Calcium, vitamin D and flavonoid supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women T-score in the osteopenic range (-1.0 > T-score > -2.5) at either the lumbar spine (LS) or femur as measured by dual energy X-ray absorptiometry (DXA) Exclusion Criteria: T-score in the osteoporotic range (T-score < -2.5) at any site Patients receiving supplements of calcium and/or vitamin D at that time or during the last 6 months Patients receiving medications known to positively or negatively affect bone turnover or BMD at that time or during the last 3 years (e.g. antiresorptive agents, oestrogens, systemic corticosteroids), or Secondary cause of osteoporosis (e.g. alcohol abuse, thyrotoxicosis etc) Patients who did not attend to their follow-up appointment and consequently had only the baseline measurements

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Calcium and vitamin D supplement<br>In this arm, 50 women will receive calcium and vitamin D supplement once per day. | Dietary Supplement: Calcium and vitamin D supplement<br>* One hundred fifty postmenopausal women with osteopenia will be randomly and blindly allocated to receive in of the 3 different dietary supplements once per day. Patients of group A will receive orally 600 mg calcium and 2400 IU vitamin D3, group B will receive the same dose of calcium and vitamin D3 plus prebiotics once per day and group C will receive the same dose of calcium, vitamin D3 plus flavonoids once per day.<br>|
| Active Comparator: Calcium, vitamin D and prebiotic supplement<br>In this arm, 50 women will receive calcium, vitamin D and prebiotic supplement once per day. | Dietary Supplement: Calcium, vitamin D and prebiotic supplement<br>* One hundred fifty postmenopausal women with osteopenia will be randomly and blindly allocated to receive in of the 3 different dietary supplements once per day. Patients of group A will receive orally 600 mg calcium and 2400 IU vitamin D3, group B will receive the same dose of calcium and vitamin D3 plus prebiotics once per day and group C will receive the same dose of calcium, vitamin D3 and flavonoids once per day.<br>|
| Active Comparator: Calcium, vitamin D, prebiotic and flavonoid supplement<br>In this arm, 50 women will receive calcium, vitamin D, prebiotic and flavonoid supplement once per day. | Dietary Supplement: Calcium, vitamin D and flavonoid supplement<br>* One hundred fifty postmenopausal women with osteopenia will be randomly and blindly allocated to receive in of the 3 different dietary supplements once per day. Patients of group A will receive orally 600 mg calcium and 2400 IU vitamin D3, group B will receive the same dose of calcium and vitamin D3 plus prebiotics once per day and group C will receive the same dose of calcium, vitamin D3 and flavonoids once per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone geometry | The primary endpoint is the within and between group change of bone geometry after 12 months of supplementation assessed by peripheral quantitative computed tomography (pQCT) of the tibia | 0 to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Areal bone mineral density (aBMD), trabecular bone score (TBS), adverse effects (tolerability) and adherence to dietary supplement after 12 months | The secondary endpoints is the within- and between-groups differences of the areal BMD (aBMD) at the lumbar spine (LS) and the total hip (TH) using dual-energy X-ray absorptiometry (DXA) and trabecular bone score (TBS) at LS, and the between-group comparison of the adverse effects (tolerability) and adherence to dietary supplement after 12 months. | 12 months | 
| Bone turnover markers, PINP and CTX | Secondary endpoint is the within- and between-group comparison change of bone turnover markers after 3, 6 and 12 months of supplementation. | 3, 6 and 12 months | 
| Change of serum TNF-α, IL-1, OPG, RANKL and IGF-1 | Secondary endpoint is the within- and between-group comparison change of TNF-α, IL-1, OPG, RANKL and IGF-1 after 3, 6 and 12 months of supplementation. | 3, 6 and 12 months | 
| Change of microMR1 Change of serum miRNAs | Secondary endpoint is the within- and between-group comparison change of miRNAs after 3, 6 and 12 months of supplementation. | 3, 6 and 12 months | 
| Change of gut microbiota | Secondary endpoint is the within- and between-group comparison change of gut microbiota after 12 months of supplementation. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary supplement for osteopenia, Calcium and vitamin D supplement, Calcium, vitamin D and prebiotics supplement, Calcium, vitamin D, prebiotics and flavonoids supplement, Bone turnover markers, Bone mineral density, Volumetric bone mineral density, Bone geometry, Postmenopausal osteopenia, Gut microbiota analysis