Clinical trial NCT04169789: Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri
Official title: Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri - A Randomized, Placebo-Controlled, Single Centre Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopausal Osteoporosis
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
Collaborators: name: BioGaia AB
First posted: 2019-11-20
Enrollment: 239
Sex: FEMALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Total tibia volumetric bone mineral density
timeFrame: 24 months
Secondary outcomes:
measure: Areal bone mineral density (aBMD) at the lumbar spine
timeFrame: 24 months
measure: Areal BMD of the total hip (DXA)
timeFrame: 0-24 months and 0-12 months
measure: Tibia trabecular bone volume fraction
timeFrame: 0-24 months and 0-12 months
measure: Tibia cortical area
timeFrame: 0-24 months and 0-12 months
measure: Tibia cortical volumetric BMD
timeFrame: 0-24 months and 0-12 months
measure: Total tibia volumetric bone mineral density
timeFrame: 12 months
measure: Blood bone formation marker procollagen type 1N propeptide (P1NP)
timeFrame: 0-24 months and 0-12 months
measure: Blood bone resorption marker C-terminal cross-linking telopeptide of type I collagen (CTX)
timeFrame: 0-24 months and 0-12 months
measure: Fecal calprotectin
timeFrame: 0-24 months and 0-12 months
measure: Fecal lipocalin-2
timeFrame: 0-24 months and 0-12 months
measure: Serum butyrate concentration
timeFrame: 0-24 months and 0-12 months
measure: Serum Wnt10b concentration
timeFrame: 0-24 months and 0-12 months
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Geriatric Medicine, Sahlgrenska University Hospital, Mölndal
state: Västra Götaland
Study officials:
affiliation: Sahlgrenska University Hospital
name: Mattias Lorentzon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.