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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteopenia; Postmenopausal Osteopenia
• Intervention / Treatment: Dietary supplement: Calcium and vitamin D supplement; Dietary supplement: Calcium, vitamin D and prebiotic supplement; Dietary supplement: Calcium, vitamin D and flavonoid supplement

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens
    • Kifissia, Athens, Greece, 14561
      • Laboratory for Research of the Musculoskeletal System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Calcium and vitamin D supplement; In this arm, 50 women will receive calcium and vitamin D supplement once per day.	Dietary supplement: Calcium and vitamin D supplement; 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.
Active Comparator: Calcium, vitamin D and prebiotic supplement; In this arm, 50 women will receive calcium, vitamin D and prebiotic supplement once per day.	Dietary supplement: Calcium, vitamin D and prebiotic supplement; 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.
Active Comparator: Calcium, vitamin D, prebiotic and flavonoid supplement; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: National Hellenic Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Bone mineral density; Bone turnover markers; Volumetric bone mineral density; Dietary supplement for osteopenia; Calcium and vitamin D supplement; Calcium, vitamin D and prebiotics supplement; Calcium, vitamin D, prebiotics and flavonoids supplement; Bone geometry; Postmenopausal osteopenia; Gut microbiota analysis
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Calcium; Vitamins; Calcium, Dietary; Ergocalciferols
• Other Study ID Numbers: 3847/22.03.2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No