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

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

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.

Study Overview

• Status: Completed
• Conditions: Postmenopausal Osteoporosis
• Intervention / Treatment: Dietary supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)

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.

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Västra Götaland
    • Gothenburg, Västra Götaland, Sweden, 43180
      • Geriatric Medicine, Sahlgrenska University Hospital, Mölndal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: L. reuteri Low Dose; 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.	Dietary supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475); L.reuteri high or low dose with cholecalciferol compared to cholecalciferol only.
ACTIVE_COMPARATOR: L. reuteri High Dose; 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.	Dietary supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475); L.reuteri high or low dose with cholecalciferol compared to cholecalciferol only.
PLACEBO_COMPARATOR: Placebo; 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.	Dietary supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475); L.reuteri high or low dose with cholecalciferol compared to cholecalciferol only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total tibia volumetric bone mineral density	Measured using high resolution peripheral computed tomography (HRpQCT), relative change 0-24 months	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 months
Areal BMD of the total hip (DXA)	Measured using DXA, relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Tibia trabecular bone volume fraction	Measured using HRpQCT, relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Tibia cortical area	Measured using HRpQCT, relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Tibia cortical volumetric BMD	Measured using HRpQCT, relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Total tibia volumetric bone mineral density	Measured using HRpQCT, relative change 0-12 months	12 months
Blood bone formation marker procollagen type 1N propeptide (P1NP)	Relative change 0-24 months and 0-12 months	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	0-24 months and 0-12 months
Fecal calprotectin	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Fecal lipocalin-2	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Serum butyrate concentration	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Serum Wnt10b concentration	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Collaborators: BioGaia AB

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2019
• Primary Completion (ACTUAL): October 18, 2022
• Study Completion (ACTUAL): October 18, 2022

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (ACTUAL): November 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal
• Other Study ID Numbers: ELBOWII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No