Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri

Postmenopausal Osteoporosis Clinical Trial

— ELBOWII  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04169789
• Other study ID #: ELBOWII
• Status: Completed
• Phase: N/A
• Start date: December 4, 2019
• Est. completion date: October 18, 2022

Study information

• Verified date: February 2023
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 239
• Est. completion date: October 18, 2022
• Est. primary completion date: October 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Postmenopausal Osteoporosis

Intervention

Dietary Supplement:
• Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)
L.reuteri high or low dose with cholecalciferol compared to cholecalciferol only.

Locations

Country	Name	City	State
Sweden	Geriatric Medicine, Sahlgrenska University Hospital, Mölndal	Gothenburg	Västra Götaland

Sponsors (2)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden	BioGaia AB

Country where clinical trial is conducted

Sweden, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total tibia volumetric bone mineral density	Measured using high resolution peripheral computed tomography (HRpQCT), relative change 0-24 months	24 months
Secondary	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
Secondary	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
Secondary	Tibia trabecular bone volume fraction	Measured using HRpQCT, relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Secondary	Tibia cortical area	Measured using HRpQCT, relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Secondary	Tibia cortical volumetric BMD	Measured using HRpQCT, relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Secondary	Total tibia volumetric bone mineral density	Measured using HRpQCT, relative change 0-12 months	12 months
Secondary	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
Secondary	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
Secondary	Fecal calprotectin	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Secondary	Fecal lipocalin-2	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Secondary	Serum butyrate concentration	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months
Secondary	Serum Wnt10b concentration	Relative change 0-24 months and 0-12 months	0-24 months and 0-12 months