Clinical trial NCT02422082: The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia
Official title: The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteopenia
Keywords: Osteopenia
Lactobacillus reuteri
Volumetric bone mineral density
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
Collaborators: name: BioGaia AB
First posted: 2015-04-21
Enrollment: 90
Sex: FEMALE
Minimum age (years): 75
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lactobacillus reuteri (L. reuteri) has been widely studied in clinical trials and has probiotic, health-promoting effects in both adults and children, and is safe for human consumption. Animal models indicate that treatment with L. reuteri has positive effects on bone metabolism and bone density. In other animal models of diabetes and the metabolic syndrome, positive effects on blood glucose and weight have been reported. The present double-blind, placebo-controlled, randomized study is designed to investigate if dietary supplementation with L. reuteri twice daily for 12 months has any effect on bone density, body composition, inflammation, or metabolic and endocrine markers in elderly women with osteopenia.

Detailed description: The role of the gut microbes for human health has gained considerable interest in recent years. Lactobacillus reuteri (L.reuteri) is a naturally occurring bacterial species in the human gut. L. reuteri has been widely studied in clinical trials of adults and children and treatment with L. reuteri is safe and is associated with health-promoting effects in humans. In animal models, L. reuteri has anti-inflammatory effects and in ovariectomized mice supplementation with L. reuteri partly prevented the bone loss induced by estrogen deficiency. Furthermore, both bone density and bone formation increased in male mice in another mice model. In mice with medically induced diabetes mellitus, L. reuteri reduced blood glucose and in a mouse model mimicking the metabolic syndrome, L. reuteri prevented diet-induced obesity. The present study is a double-blind, placebo-controlled, randomized, study in 90 elderly women with osteopenia recruited from the population. These women will be treated with L. reuteri or placebo orally twice daily for 12 months. The effects on bone will be investigated with dual energy x-ray absorptiometry, high-resolution peripheral quantitative computed tomography, and bone turnover markers. Hormones and markers of inflammation and metabolism will be followed as well as changes in the gut microbiota composition.

Eligibility criteria: Inclusion Criteria:

* bone mineral density T-score less than -1 but more than -2.5 in the total hip or femoral neck or lumbar spine (L1-L4) by dual energy x-ray absorptiometry
* signed informed consent
* stated availability throughout the entire study period
* mental ability to understand and willingness to fulfill all the details of the protocol

Exclusion Criteria:

* untreated hyperthyroidism
* rheumatoid arthritis
* diagnosed with disease causing secondary osteoporosis within the last year, including primary hyperparathyroidism, chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, or diabetes
* recently diagnosed malignancy (within the last 5 years)
* per oral corticosteroid use
* use of antiresorptive therapy, including systemic hormone replacement therapy, bisphosphonates, strontium ran elate
* use of teriparatide (current or during the last 3 years)
* participation in other clinical interventional trials
* use of antibiotics within 2 months preceding the inclusion

Primary outcomes:
measure: Total tibia volumetric bone mineral density
timeFrame: 12 months
Secondary outcomes:
measure: Trabecular volumetric bone mineral density
timeFrame: 12 months
measure: Cortical volumetric bone mineral density
timeFrame: 12 months
measure: Cortical thickness
timeFrame: 12 months
measure: Cortical porosity
timeFrame: 12 months
measure: Areal bone mineral density
timeFrame: 12 months
measure: Bone material strength index
timeFrame: 12 months
measure: Blood pressure
timeFrame: 12 months
measure: Change in gut microbiota composition
timeFrame: 3-12 months
measure: Ultrasensitive C-reactive protein
timeFrame: 3-12 months
measure: Interleukin-10
timeFrame: 3-12 months
measure: Interleukin-17
timeFrame: 3-12 months
measure: Tumor-necrosis factor-alpha
timeFrame: 3-12 months
measure: Tartrate-resistent alkaline phosphatase 5b
timeFrame: 3-12 months
measure: Cross-linked N-terminal telopeptide
timeFrame: 3-12 months
measure: Bone-specific alkaline phosphatase
timeFrame: 3-12 months
measure: Receptor activator of nuclear factor kappa B (RANK)
timeFrame: 3-12 months
measure: Receptor activator of nuclear factor kappa B ligand (RANK-ligand)
timeFrame: 3-12 months
measure: Osteocalcin
timeFrame: 3-12 months
measure: Blood glucose
timeFrame: 3-12 months
measure: Haemoglobin A1C
timeFrame: 3-12 months
measure: Apolipoprotein A1 (ApoA1)
timeFrame: 3-12 months
measure: Apolipoprotein B (ApoB)
timeFrame: 3-12 months
measure: Cholesterol
timeFrame: 3-12 months
measure: High density lipoprotein (HDL)
timeFrame: 3-12 months
measure: Low density lipoprotein (LDL)
timeFrame: 3-12 months
measure: Triglycerides
timeFrame: 3-12 months
measure: Oxytocin
timeFrame: 3-12 months
measure: Estradiol
timeFrame: 3-12 months
measure: Leptin
timeFrame: 3-12 months
measure: Adiponectin
timeFrame: 3-12 months
measure: Testosterone
timeFrame: 3-12 months
measure: Lean mass
timeFrame: 12 months
measure: Fat mass
timeFrame: 12 months
Other outcomes:
Locations:
city: Mölndal
country: Sweden
facility: Geriatric Medicine, Mölndal Hospital
state: Västra Götaland
Study officials:
affiliation: Dept Geriatrics, Sahlgrenska University Hospital
name: Mattias Lorentzon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Reid G, Kim SO, Kohler GA. Selecting, testing and understanding probiotic microorganisms. FEMS Immunol Med Microbiol. 2006 Mar;46(2):149-57. doi: 10.1111/j.1574-695X.2005.00026.x.
citation: Britton RA, Irwin R, Quach D, Schaefer L, Zhang J, Lee T, Parameswaran N, McCabe LR. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol. 2014 Nov;229(11):1822-30. doi: 10.1002/jcp.24636.
citation: McCabe LR, Irwin R, Schaefer L, Britton RA. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice. J Cell Physiol. 2013 Aug;228(8):1793-8. doi: 10.1002/jcp.24340.
citation: Fak F, Backhed F. Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice. PLoS One. 2012;7(10):e46837. doi: 10.1371/journal.pone.0046837. Epub 2012 Oct 9.