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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02422082
Recruitment Status : Completed
First Posted : April 21, 2015
Last Update Posted : April 18, 2018
Sponsor:
Collaborator:
BioGaia AB
Information provided by (Responsible Party):
Mattias Lorentzon, Sahlgrenska University Hospital, Sweden

Tracking Information
First Submitted Date  ICMJE April 10, 2015
First Posted Date  ICMJE April 21, 2015
Last Update Posted Date April 18, 2018
Actual Study Start Date  ICMJE May 8, 2015
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
Total tibia volumetric bone mineral density [ Time Frame: 12 months ]
Change in percent in total tibia volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
Total tibia volumetric bone mineral density [ Time Frame: 12 months ]
Change in total tibia volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
  • Trabecular volumetric bone mineral density [ Time Frame: 12 months ]
    Change in percent in trabecular volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Cortical volumetric bone mineral density [ Time Frame: 12 months ]
    Change in percent in cortical volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Cortical thickness [ Time Frame: 12 months ]
    Change in percent in cortical thickness compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Cortical porosity [ Time Frame: 12 months ]
    Change in percent in cortical porosity compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Areal bone mineral density [ Time Frame: 12 months ]
    Change in percent in areal bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Bone material strength index [ Time Frame: 12 months ]
    Change in percent in bone material strength index compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Blood pressure [ Time Frame: 12 months ]
    Change in percent in blood pressure compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Change in gut microbiota composition [ Time Frame: 3-12 months ]
    Change in percent in gut microbiota composition compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Ultrasensitive C-reactive protein [ Time Frame: 3-12 months ]
    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
  • Interleukin-10 [ Time Frame: 3-12 months ]
    Change in percent in interleukin-10 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Interleukin-17 [ Time Frame: 3-12 months ]
    Change in percent in interleukin-17 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Tumor-necrosis factor-alpha [ Time Frame: 3-12 months ]
    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
  • Tartrate-resistent alkaline phosphatase 5b [ Time Frame: 3-12 months ]
    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
  • Cross-linked N-terminal telopeptide [ Time Frame: 3-12 months ]
    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
  • Bone-specific alkaline phosphatase [ Time Frame: 3-12 months ]
    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
  • Receptor activator of nuclear factor kappa B (RANK) [ Time Frame: 3-12 months ]
    Change in percent in RANK in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Receptor activator of nuclear factor kappa B ligand (RANK-ligand) [ Time Frame: 3-12 months ]
    Change in percent in RANK-ligand in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Osteocalcin [ Time Frame: 3-12 months ]
    Change in percent in osteocalcin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Blood glucose [ Time Frame: 3-12 months ]
    Change in percent in blood glucose compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Haemoglobin A1C [ Time Frame: 3-12 months ]
    Change in percent in haemoglobin A1C compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Apolipoprotein A1 (ApoA1) [ Time Frame: 3-12 months ]
    Change in percent in ApoA1 compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Apolipoprotein B (ApoB) [ Time Frame: 3-12 months ]
    Change in percent in ApoB compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Cholesterol [ Time Frame: 3-12 months ]
    Change in percent in cholesterol compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • High density lipoprotein (HDL) [ Time Frame: 3-12 months ]
    Change in percent in HDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Low density lipoprotein (LDL) [ Time Frame: 3-12 months ]
    Change in percent in LDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Triglycerides [ Time Frame: 3-12 months ]
    Change in percent in triglycerides compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Oxytocin [ Time Frame: 3-12 months ]
    Change in percent in oxytocin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Estradiol [ Time Frame: 3-12 months ]
    Change in percent in estradiol in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Leptin [ Time Frame: 3-12 months ]
    Change in percent in leptin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Adiponectin [ Time Frame: 3-12 months ]
    Change in percent in adiponectin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Testosterone [ Time Frame: 3-12 months ]
    Change in percent in testosterone in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Lean mass [ Time Frame: 12 months ]
    Change in percent in lean mass compared to placebo after 12 months of dietary supplementation with L. reuteri
  • Fat mass [ Time Frame: 12 months ]
    Change in percent in fat mass compared to placebo after 12 months of dietary supplementation with L. reuteri
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
  • Trabecular volumetric bone mineral density [ Time Frame: 12 months ]
    Change in trabecular volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Cortical volumetric bone mineral density [ Time Frame: 12 months ]
    Change in cortical volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Cortical thickness [ Time Frame: 12 months ]
    Change in cortical thickness compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Cortical porosity [ Time Frame: 12 months ]
    Change in cortical porosity compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Areal bone mineral density [ Time Frame: 12 months ]
    Change in areal bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri
  • Change in gut microbiota composition [ Time Frame: 3-12 months ]
    Change in gut microbiota composition compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Ultrasensitive C-reactive protein [ Time Frame: 3-12 months ]
    Change in ultrasensitive C-reactive protein in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Interleukin-10 [ Time Frame: 3-12 months ]
    Change in interleukin-10 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Interleukin-17 [ Time Frame: 3-12 months ]
    Change in interleukin-17 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Tumor-necrosis factor-alpha [ Time Frame: 3-12 months ]
    Change in tumor-necrosis factor-alpha in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Tartrate-resistent alkaline phosphatase 5b [ Time Frame: 3-12 months ]
    Change in tartrate-resistent alkaline phosphatase 5b in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Cross-linked N-terminal telopeptide [ Time Frame: 3-12 months ]
    Change in cross-linked N-terminal telopeptide in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Bone-specific alkaline phosphatase [ Time Frame: 3-12 months ]
    Change in bone-specific alkaline phosphatase in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • RANK [ Time Frame: 3-12 months ]
    Change in RANK in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • RANK-ligand [ Time Frame: 3-12 months ]
    Change in RANK-ligand in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Osteocalcin [ Time Frame: 3-12 months ]
    Change in osteocalcin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Blood glucose [ Time Frame: 3-12 months ]
    Change in blood glucose compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Haemoglobin A1C [ Time Frame: 3-12 months ]
    Change in haemoglobin A1C compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • ApoA1 [ Time Frame: 3-12 months ]
    Change in ApoA1 compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • ApoB [ Time Frame: 3-12 months ]
    Change in ApoB compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Cholesterol [ Time Frame: 3-12 months ]
    Change in cholesterol compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • HDL [ Time Frame: 3-12 months ]
    Change in HDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • LDL [ Time Frame: 3-12 months ]
    Change in LDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Triglycerides [ Time Frame: 3-12 months ]
    Change in triglycerides compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Oxytocin [ Time Frame: 3-12 months ]
    Change in oxytocin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Estradiol [ Time Frame: 3-12 months ]
    Change in estradiol in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Leptin [ Time Frame: 3-12 months ]
    Change in leptin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Adiponectin [ Time Frame: 3-12 months ]
    Change in adiponectin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Testosterone [ Time Frame: 3-12 months ]
    Change in testosterone in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri
  • Lean mass [ Time Frame: 12 months ]
    Change in lean mass compared to placebo after 12 months of dietary supplementation with L. reuteri
  • Fat mass [ Time Frame: 12 months ]
    Change in fat mass compared to placebo after 12 months of dietary supplementation with L. reuteri
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia
Official Title  ICMJE The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Osteopenia
Intervention  ICMJE
  • Dietary Supplement: L. reuteri
    Dietary supplementation with L. reuteri twice daily for 12 months
    Other Name: Lactobacillus reuteri ATCC PTA 6475
  • Dietary Supplement: Placebo
    Dietary supplementation with placebo twice daily for 12 months
Study Arms  ICMJE
  • Active Comparator: L. reuteri
    Lactobacillus reuteri (L. reuteri) ATCC PTA 6475 at a dose of 5 000 000 000 CFU as a powder in a stick-pack, orally twice daily (morning and evening) yielding a total daily dose of 10 000 000 000 CFU per day, for 12 months.
    Intervention: Dietary Supplement: L. reuteri
  • Placebo Comparator: Placebo
    Placebo product identical to the active product (L. reuteri) in taste and appearance but without the active component, orally twice daily, for 12 months.
    Intervention: Dietary Supplement: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2015)
90
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 1, 2017
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 75 Years to 80 Years   (Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02422082
Other Study ID Numbers  ICMJE LRvBMD
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Mattias Lorentzon, Sahlgrenska University Hospital, Sweden
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Sahlgrenska University Hospital, Sweden
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE BioGaia AB
Investigators  ICMJE
Principal Investigator: Mattias Lorentzon, MD, PhD Dept Geriatrics, Sahlgrenska University Hospital
PRS Account Sahlgrenska University Hospital, Sweden
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP