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

Sahlgrenska University Hospital

Status: Completed

Conditions: Postmenopausal Osteoporosis

Treatments: Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04169789

ELBOWII

Details and patient eligibility

About

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.

Full 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.

Enrollment: 239 patients

Sex: Female

Ages: 45+ years old

Volunteers: Accepts 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

239 participants in 3 patient groups, including a placebo group

L. reuteri Low Dose

Active Comparator group

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.

Treatment:

Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)

L. reuteri High Dose

Active Comparator group

Description:

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.

Treatment:

Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)