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Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri (ELBOWII)

Primary Purpose

Postmenopausal Osteoporosis

Status

Completed

Phase

Not Applicable

Locations

Sweden

Study Type

Interventional

Intervention

Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)

About this trial

This is an interventional treatment trial for Postmenopausal Osteoporosis

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

Postmenopausal women, 45 years or older, within 1-4 years from their last menses.
Vitamin D levels above 25 nmol/L.
Signed informed consent.
Stated availability throughout the entire study period.
Ability to understand study instructions and willingness to adhere to the protocol.

Exclusion Criteria:

Bone mineral density of < -2.5 combined with a fracture risk assessment tool (FRAX) score of 20% or higher for major osteoporotic fracture.
Severe osteoporosis, defined as bone mineral density of < -3.0 in either the total hip, femur neck or lumbar spine L1-L4.
Vertebral fracture (grade II or III) diagnosed using lateral spine imaging with DXA.
Untreated hyperthyroidism or hyperthyroidism within the last 5 years.
Known untreated hyperparathyroidism.
Rheumatoid arthritis.
Diagnosed with disease causing secondary osteoporosis, including chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, or diabetes mellitus.
Recently diagnosed malignancy (within the last 5 years).
Oral corticosteroid use.
Previous (within the last 5 years) use of antiresorptive therapy, including systemic hormone therapy (estrogen), bisphosphonates, strontium ranelate or denosumab.
Systemic skeletal disease (including e.g. Paget's disease and osteogenesis imperfecta).
Any systemic disease that could affect bone loss, as judged by the investigator.
Use of teriparatide (current or during the last 3 years).
Participation in other clinical trials.
Current antibiotics treatment or within the last 2 months prior to inclusion.
Current and within the past 2 months use of probiotic supplement
Vitamin D deficiency (25-OH vitamin D<25 nmol/l)
Hypo- or hypercalcemia.
Osteosynthesis materials in both lower legs (tibia).

Sites / Locations

Geriatric Medicine, Sahlgrenska University Hospital, Mölndal

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Arm Label

L. reuteri Low Dose

L. reuteri High Dose

Placebo

Arm Description

Capsules of freeze-dried L. reuteri 6475 of 5x10E8 colony-forming units (CFU) mixed with maltodextrin powder and 200 IU of cholecalciferol, taken twice daily for 24 months, yielding a total dose of either 1x10E9 L.reuteri CFU and 400 IU of cholecalciferol per day.

Capsules of freeze-dried L. reuteri 6475 of 5x10E9 colony-forming units (CFU) mixed with maltodextrin powder and 200 IU of cholecalciferol, taken twice daily for 24 months, yielding a total daily dose of 1x10E10 L.reuteri CFU and 400 IU of cholecalciferol per day.

Placebo product identical to the active product (L. reuteri) in taste and appearance but without the active component, orally twice daily, for 24 months.The placebo product contains 200 IU cholecalciferol per dose, yielding a total dose of cholecalciferol of 400 IU per day.

Outcomes

Primary Outcome Measures

Total tibia volumetric bone mineral density

Measured using high resolution peripheral computed tomography (HRpQCT), relative change 0-24 months

Secondary Outcome Measures

Areal bone mineral density (aBMD) at the lumbar spine

Measured using dual x-ray absorptiometry (DXA), relative change 0-24 months and 0-12 months

Areal BMD of the total hip (DXA)

Measured using DXA, relative change 0-24 months and 0-12 months

Tibia trabecular bone volume fraction

Measured using HRpQCT, relative change 0-24 months and 0-12 months

Tibia cortical area

Measured using HRpQCT, relative change 0-24 months and 0-12 months

Tibia cortical volumetric BMD

Measured using HRpQCT, relative change 0-24 months and 0-12 months

Total tibia volumetric bone mineral density

Measured using HRpQCT, relative change 0-12 months

Blood bone formation marker procollagen type 1N propeptide (P1NP)

Relative change 0-24 months and 0-12 months

Blood bone resorption marker C-terminal cross-linking telopeptide of type I collagen (CTX)

Relative change 0-24 months and 0-12 months

Fecal calprotectin

Relative change 0-24 months and 0-12 months

Fecal lipocalin-2

Relative change 0-24 months and 0-12 months

Serum butyrate concentration

Relative change 0-24 months and 0-12 months

Serum Wnt10b concentration

Relative change 0-24 months and 0-12 months

Full Information

NCT ID

NCT04169789

First Posted

November 18, 2019

Last Updated

February 3, 2023

Sponsor

Sahlgrenska University Hospital, Sweden

Collaborators

BioGaia AB

1. Study Identification

Unique Protocol Identification Number

NCT04169789

Brief Title

Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri

Acronym

ELBOWII

Official Title

Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri - A Randomized, Placebo-Controlled, Single Centre Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

December 4, 2019 (Actual)

Primary Completion Date

October 18, 2022 (Actual)

Study Completion Date

October 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sahlgrenska University Hospital, Sweden

Collaborators

BioGaia AB

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study evaluates the effect of two different doses of Lactobacillus reuteri ATCC PTA 6475 (L.reuteri 6475) on bone loss in early postmenopausal women. One third of the participants will be randomised to the lower dose, one third to the higher dose and one third to placebo.

Detailed Description

We have previously shown that daily supplementation of the probiotic Lactobacillus reuteri ATCC PTA 6475 (10E10 colony-forming units (CFU)) was able to reduce bone loss over 12 months in 76-year-old women compared to placebo. It is not known if the probiotic is effective over longer time periods or if the effect is dose-dependent. The aim of this study is to investigate if two different doses of Lactobacillus reuteri ATCC PTA 6475 (total daily dose of either 1x10E9 or 1x10E10 CFU/day) can prevent or reduce bone loss, compared to placebo, in early (1-4 years since last menses) postmenopausal women over 24 months. All women will receive 400 IU of vitamin D (cholecalciferol) per day. Changes in bone mineral density, bone geometry and microstructure will be measured using dual x-ray absorptiometry and high resolution peripheral computed tomography.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Postmenopausal Osteoporosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

239 (Actual)

8. Arms, Groups, and Interventions

Arm Title

L. reuteri Low Dose

Arm Type

Active Comparator

Arm Description

Arm Title

L. reuteri High Dose

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Dietary Supplement

Intervention Name(s)

Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)

Intervention Description

L.reuteri high or low dose with cholecalciferol compared to cholecalciferol only.

Primary Outcome Measure Information:

Title

Total tibia volumetric bone mineral density

Description

Measured using high resolution peripheral computed tomography (HRpQCT), relative change 0-24 months

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Areal bone mineral density (aBMD) at the lumbar spine

Description

Measured using dual x-ray absorptiometry (DXA), relative change 0-24 months and 0-12 months

Time Frame

24 months

Title

Areal BMD of the total hip (DXA)

Description

Measured using DXA, relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Tibia trabecular bone volume fraction

Description

Measured using HRpQCT, relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Tibia cortical area

Description

Measured using HRpQCT, relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Tibia cortical volumetric BMD

Description

Measured using HRpQCT, relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Total tibia volumetric bone mineral density

Description

Measured using HRpQCT, relative change 0-12 months

Time Frame

12 months

Title

Blood bone formation marker procollagen type 1N propeptide (P1NP)

Description

Relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Blood bone resorption marker C-terminal cross-linking telopeptide of type I collagen (CTX)

Description

Relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Fecal calprotectin

Description

Relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Fecal lipocalin-2

Description

Relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Serum butyrate concentration

Description

Relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

Title

Serum Wnt10b concentration

Description

Relative change 0-24 months and 0-12 months

Time Frame

0-24 months and 0-12 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Postmenopausal women, 45 years or older, within 1-4 years from their last menses. Vitamin D levels above 25 nmol/L. Signed informed consent. Stated availability throughout the entire study period. Ability to understand study instructions and willingness to adhere to the protocol. Exclusion Criteria: Bone mineral density of < -2.5 combined with a fracture risk assessment tool (FRAX) score of 20% or higher for major osteoporotic fracture. Severe osteoporosis, defined as bone mineral density of < -3.0 in either the total hip, femur neck or lumbar spine L1-L4. Vertebral fracture (grade II or III) diagnosed using lateral spine imaging with DXA. Untreated hyperthyroidism or hyperthyroidism within the last 5 years. Known untreated hyperparathyroidism. Rheumatoid arthritis. Diagnosed with disease causing secondary osteoporosis, including chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, or diabetes mellitus. Recently diagnosed malignancy (within the last 5 years). Oral corticosteroid use. Previous (within the last 5 years) use of antiresorptive therapy, including systemic hormone therapy (estrogen), bisphosphonates, strontium ranelate or denosumab. Systemic skeletal disease (including e.g. Paget's disease and osteogenesis imperfecta). Any systemic disease that could affect bone loss, as judged by the investigator. Use of teriparatide (current or during the last 3 years). Participation in other clinical trials. Current antibiotics treatment or within the last 2 months prior to inclusion. Current and within the past 2 months use of probiotic supplement Vitamin D deficiency (25-OH vitamin D<25 nmol/l) Hypo- or hypercalcemia. Osteosynthesis materials in both lower legs (tibia).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mattias Lorentzon, MD, PhD

Organizational Affiliation

Sahlgrenska University Hospital, Sweden

Official's Role

Principal Investigator

Facility Information:

Facility Name

Geriatric Medicine, Sahlgrenska University Hospital, Mölndal

City

Gothenburg

State/Province

Västra Götaland

ZIP/Postal Code

43180

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29926979

Citation

Nilsson AG, Sundh D, Backhed F, Lorentzon M. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018 Sep;284(3):307-317. doi: 10.1111/joim.12805. Epub 2018 Jul 22.

Results Reference

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Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri

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