The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia

Osteopenia Clinical Trial

Official title:

The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02422082
• Other study ID #: LRvBMD
• Status: Completed
• Phase: N/A
• First received: April 10, 2015
• Last updated: April 17, 2018
• Start date: May 8, 2015
• Est. completion date: December 1, 2017

Study information

• Verified date: April 2018
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 1, 2017
• Est. primary completion date: September 15, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 75 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Bone Diseases, Metabolic
• Osteopenia

Intervention

Dietary Supplement:
• L. reuteri
Dietary supplementation with L. reuteri twice daily for 12 months
• Placebo
Dietary supplementation with placebo twice daily for 12 months

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden	BioGaia AB

Country where clinical trial is conducted

Sweden, 

References & Publications (5)

Adams MR, Marteau P. On the safety of lactic acid bacteria from food. Int J Food Microbiol. 1995 Oct;27(2-3):263-4. — View 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. — View Citation

Fåk F, Bäckhed 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. — View 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. — View Citation

Reid G, Kim SO, Köhler GA. Selecting, testing and understanding probiotic microorganisms. FEMS Immunol Med Microbiol. 2006 Mar;46(2):149-57. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total tibia volumetric bone mineral density	Change in percent in total tibia volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Trabecular volumetric bone mineral density	Change in percent in trabecular volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Cortical volumetric bone mineral density	Change in percent in cortical volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Cortical thickness	Change in percent in cortical thickness compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Cortical porosity	Change in percent in cortical porosity compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Areal bone mineral density	Change in percent in areal bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Bone material strength index	Change in percent in bone material strength index compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Blood pressure	Change in percent in blood pressure compared to placebo group after 1 year of dietary supplementation with L. reuteri	12 months
Secondary	Change in gut microbiota composition	Change in percent in gut microbiota composition compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Ultrasensitive C-reactive protein	Change in percent in ultrasensitive C-reactive protein in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Interleukin-10	Change in percent in interleukin-10 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Interleukin-17	Change in percent in interleukin-17 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Tumor-necrosis factor-alpha	Change in percent in tumor-necrosis factor-alpha in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Tartrate-resistent alkaline phosphatase 5b	Change in percent in tartrate-resistent alkaline phosphatase 5b in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Cross-linked N-terminal telopeptide	Change in percent in cross-linked N-terminal telopeptide in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Bone-specific alkaline phosphatase	Change in percent in bone-specific alkaline phosphatase in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Receptor activator of nuclear factor kappa B (RANK)	Change in percent in RANK in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Receptor activator of nuclear factor kappa B ligand (RANK-ligand)	Change in percent in RANK-ligand in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Osteocalcin	Change in percent in osteocalcin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Blood glucose	Change in percent in blood glucose compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Haemoglobin A1C	Change in percent in haemoglobin A1C compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Apolipoprotein A1 (ApoA1)	Change in percent in ApoA1 compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Apolipoprotein B (ApoB)	Change in percent in ApoB compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Cholesterol	Change in percent in cholesterol compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	High density lipoprotein (HDL)	Change in percent in HDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Low density lipoprotein (LDL)	Change in percent in LDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Triglycerides	Change in percent in triglycerides compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Oxytocin	Change in percent in oxytocin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Estradiol	Change in percent in estradiol in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Leptin	Change in percent in leptin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Adiponectin	Change in percent in adiponectin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Testosterone	Change in percent in testosterone in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri	3-12 months
Secondary	Lean mass	Change in percent in lean mass compared to placebo after 12 months of dietary supplementation with L. reuteri	12 months
Secondary	Fat mass	Change in percent in fat mass compared to placebo after 12 months of dietary supplementation with L. reuteri	12 months