Back to resultsEffect of VSL#3 on Bone Mineral Density in Postmenopausal Women (ProBoneVSL)
Primary Purpose
Menopausal Osteoporosis
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
VSL#3
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Menopausal Osteoporosis focused on measuring Probiotics, Menopausal Osteoporosis
Eligibility Criteria
Inclusion Criteria:
- Willing and able to give written informed consent for participation in the study
- Age range 50-65 years
- Menopausal status (defined by >1 yr since last menstrual period or follicle stimulating hormone (FSH) level in the postmenopausal range)
- Ambulatory
- Body mass Index (BMI) must be ≥ 18 and ≤ 32 kg/m2 at screening
- Bone mineral density (BMD), expressed as T-scores, must be > - 2.5 in the lumbar spine (L1-L4), the femoral neck, and the total hip, as measured by DEXA
- Commitment not to use any products that may influence the study outcome
- Ability to understand and comply with the requirements of the study
Exclusion Criteria:
- Premenopausal status
- History of >1 previous atraumatic bone fractures after age 50
- Presence of established osteoporosis (T-score ≤ - 2.5, in the lumbar spine, femoral neck or total hip as measured by screening DEXA)
- History of immunological or bone-related disorders including: HIV infection, Type I diabetes mellitus, bone marrow or organ transplantation; Inflammatory bowel disease (ulcerative colitis, Crohn's disease); multiple myeloma; osteomalacia; osteosarcoma; Paget's disease; rheumatoid arthritis; systemic lupus erythematous; parathyroid disorders
- Uncontrolled type II diabetes mellitus (HgbA1c ≥ 7% within the last 12 months)
- History of bariatric surgery or other forms of malabsorption (including documented celiac disease, or chronic diarrhea)
- Alcohol abuse
- Clinically significant chronic kidney disease (stage ≥ 2, with total serum creatinine level > 2.5 mg/dL and calculated glomerular filtration rate (GFR) < 60 mL/min by the Modification of Diet in Renal Disease (MDRD equation)
- Clinically significant cardiovascular disease (myocardial infarction, cerebral vascular accident or acute congestive heart failure within the previous 12 months
- Any malignancies, other than localized skin squamous cell carcinoma, diagnosed within the previous 5 years, or any history of metastatic cancer
- History of use of oral supplement products containing probiotic bacteria (more than once per week) within four weeks prior to baseline
- Current use (within the past 8 weeks) of any medication with known influences on the immune or skeletal system (e.g. immune modulation therapy, systemic glucocorticoids, systemic steroid hormones
- Use of oral or injectable bisphosphonates for more than 1 year within the last 5 years
- Current or past use (within 1 year) of Denosumab, Teriparatide, Raloxifene, hormone replacement therapy (HRT), calcitonin, or any other anti-resorptive agent other than bisphosphonates used for the prevention and treatment of osteoporosis
- Use of antibiotics during the previous two months or frequent user of antibiotics (>2 courses during the previous 12 months) for any cause
- Smoking or use of nicotine-containing products during the last six months
- Known hypersensitivity to any of the ingredients in the VSL#3 or the placebo study drug
- serum or plasma 25-hydroxyvitamin D [25(OH)D] concentration < 12 ng/mL
- uncontrolled thyroid disease (abnormal blood thyroid stimulating hormone (TSH) level within the last 12 months and/or changing dose of thyroid replacement therapy within the last 12 months)
Sites / Locations
- Emory University Hospital Clinical Research Network, Emory Clinic, Emory St. Joseph's Hospital, Emory University Hospital (non-CRN)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
VSL#3
Control
Arm Description
VSL#3 two active sachets [containing 450x109 colony-forming units (CFU)/sachet], taken daily in a single administration.
Placebo, no supplemental probiotics.
Outcomes
Primary Outcome Measures
Change in Bone Mineral Density (BMD) of the Lumbar Spine (L1-L4 Segment) as Measured by Dual Energy X-ray Absorptiometry (DEXA)
All DEXA scans will be performed on the same device using a GE Lunar iDEXA machine. Participants will be asked to lie still on a scanning table with their arms at their sides for approximately 10 minutes.
Secondary Outcome Measures
Change in Bone Density of the Non-dominant Hip (Femoral Neck and Total Hip Area) as Measured by DEXA (Dual Energy X-ray Absorptiometry).
All DEXA scans will be performed on the same device using a GE Lunar iDEXA machine. Participants will be asked to lie still on a scanning table with their arms at their sides for approximately 10 minutes.
Change in Serum Collagen Type 1 Cross-linked C-telopeptide (CTX) Concentrations (a Marker of Bone Resorption).
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Change in Serum Procollagen Type I N Propeptide (PINP) - a Marker of Bone Formation - Concentrations.
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Change in Serum Free Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) Concentrations.
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Change in Serum Osteoprotegrin (OPG) Concentrations.
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Change in Serum Tumor Necrosis Factor (TNF)
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Change in Serum Interleukin-17 (IL-17) Concentrations.
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Number of Unused Study Drug Sachets.
This will be determined by contacts (twice monthly telephone or at research center visits) of the study coordinator with each subject and responses to three standardized question areas: 1) "Are you having any difficulty, problems or new symptoms with the study medication?" 2) If yes, "What has the problem been?" and 3) "Have you missed any of your study drug doses, and if so how many in the previous 2 week period?" Appropriate notations based on subject responses will be documented in the case report form (CRF). Subjects will be instructed at study entry and reminded via serial contacts to return all of their used and unused drug sachets at each research center visit. Unused and used study drug sachets will be tallied and recorded in the CRF by the study coordinator serially for the entire study.
Gastrointestinal Symptom Rating
Study drug tolerance will be assessed by obtaining serial measures of the Gastrointestinal Symptom Rating Scale (GSRS). These will be obtained with in-person interviews at the baseline and month 6 and 12 visits and by telephone contact with all subjects by the study coordinator every 2 weeks. Data will be analyzed within the 5 symptom domains depicting symptoms related to gastric reflux, abdominal pain, indigestion, diarrhea, and constipation.The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. A GSRS total score, the sum of all 5 domains, will also be assessed.
Study Retention Rate.
The number of participants who complete all study visits, phone calls, and maintain drug compliance. Retention will be documented via conventional Consolidated Standards of Reporting Trials (CONSORT) criteria and documentation of missed study visits, missed telephone communications and compliance with study drug administration. All data will be maintained in the CRFs.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03165747
Brief Title
Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women
Acronym
ProBoneVSL
Official Title
Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women: a Pilot Randomized, Placebo-Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
Investigator terminated trial pursuant to research contract rights.
Study Start Date
October 1, 2017 (Actual)
Primary Completion Date
March 23, 2019 (Actual)
Study Completion Date
March 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Osteoporosis has a devastating impact on quality of life of postmenopausal women, and is a significant cause of disability and morbidity. Many drugs are approved for the prevention and treatment of osteoporosis, but are associated with high costs and side effects. Some data from animal studies suggests that supplementation with probiotics can safely treat and prevent osteoporosis. The probiotic VSL#3 is commercially available, is safe for human consumption, and has been widely used in human clinical trials, and has known health-promoting effects in both children and adults.
The double-blind, randomized, placebo-controlled trial of VSL#3 will be conducted for 12 months in 40 postmenopausal women to determine if VSL#3 improves bone mineral density and related bone markers. Study visits will include all or some of the following procedures: a medical exam, urine collection, height and weight measurement, a blood draw to assess bone biomarkers, a DEXA (dual energy X-ray absorptiometry) scan to measure bone density, and health questionnaires.
This is one of the first clinical trials proposed to investigate the effects of probiotics in bone in humans. If successful, this proposal will provide the first evidence that nutritional supplementation with the probiotic VSL#3 is a safe and effective strategy for preventing postmenopausal bone loss.
Detailed Description
Osteoporosis has a devastating impact on quality of life of postmenopausal women, and is a significant cause of disability and morbidity. Many drugs are approved for the prevention and treatment of osteoporosis, but are associated with high costs and side effects. Some data from animal studies suggests that supplementation with probiotics can safely treat and prevent osteoporosis. The probiotic VSL#3 is commercially available, is safe for human consumption, and has been widely used in human clinical trials, and has known health-promoting effects in both children and adults.
The double-blind, randomized, placebo-controlled trial of VSL#3 will be conducted in a population of ambulatory, otherwise healthy, postmenopausal women for 12 months. Control and VSL#3-treated postmenopausal women will be matched by age (± 3 years). Study visits will include all or some of the following procedures: a medical exam, urine collection, height and weight measurement, a blood draw to assess bone biomarkers, a dual energy X-ray absorptiometry (DEXA) scan to measure bone density, and health questionnaires.
The primary endpoint is the change in bone mineral density (BMD) at the L1-4 lumbar spine over one year of study. Changes in BMD at the femoral neck and total hip area will be secondary endpoints. All BMD data will also be used as a tool for future studies power calculation and design. Additional endpoints will include changes in bone turnover markers and inflammatory/osteoclastogenic cytokines. Measurements of indices of bone turnover and cytokine levels will provide much needed mechanistic information.The data will allow to establish whether VSL#3 prevents bone loss and/or increases bone mass by regulating bone resorption, formation, or both.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menopausal Osteoporosis
Keywords
Probiotics, Menopausal Osteoporosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Only the Emory Investigational Drug Service (IDS) pharmacy will know which dose of probiotic was given to the subject. The study team, parents, subjects, individuals entering the data, statistician, individuals performing laboratory tests and DEXA scans, research center nurses and investigators will remain blinded as to which treatment the subjects received. Each subject will be assigned a unique identifier, which will be used in the database. In addition, all lab specimens will only include the patient's unique identifier. Permuted block sizes will not be disclosed to the blinded study personnel to minimize the likelihood of their being able to predict the next randomization assignment in the series. Investigators and all study personnel will remain blinded until the final subject has completed her final visit and primary and secondary endpoints have been analyzed.
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VSL#3
Arm Type
Experimental
Arm Description
VSL#3 two active sachets [containing 450x109 colony-forming units (CFU)/sachet], taken daily in a single administration.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Placebo, no supplemental probiotics.
Intervention Type
Drug
Intervention Name(s)
VSL#3
Intervention Description
8 strains of live bacteria: Bifidobacterium breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. bulgaricus and Streptococcus thermophilus. 900 billion CFU taken orally daily in a single administration.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Two placebo sachets taken orally daily in a single administration.
Primary Outcome Measure Information:
Title
Change in Bone Mineral Density (BMD) of the Lumbar Spine (L1-L4 Segment) as Measured by Dual Energy X-ray Absorptiometry (DEXA)
Description
All DEXA scans will be performed on the same device using a GE Lunar iDEXA machine. Participants will be asked to lie still on a scanning table with their arms at their sides for approximately 10 minutes.
Time Frame
Baseline and 12-month visit.
Secondary Outcome Measure Information:
Title
Change in Bone Density of the Non-dominant Hip (Femoral Neck and Total Hip Area) as Measured by DEXA (Dual Energy X-ray Absorptiometry).
Description
All DEXA scans will be performed on the same device using a GE Lunar iDEXA machine. Participants will be asked to lie still on a scanning table with their arms at their sides for approximately 10 minutes.
Time Frame
Baseline and 12-month visit.
Title
Change in Serum Collagen Type 1 Cross-linked C-telopeptide (CTX) Concentrations (a Marker of Bone Resorption).
Description
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Time Frame
Baseline, 6-month, 12-month visits
Title
Change in Serum Procollagen Type I N Propeptide (PINP) - a Marker of Bone Formation - Concentrations.
Description
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Time Frame
Baseline, 6-month, 12-month visits
Title
Change in Serum Free Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) Concentrations.
Description
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Time Frame
Baseline, 6-month, 12-month visits
Title
Change in Serum Osteoprotegrin (OPG) Concentrations.
Description
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Time Frame
Baseline, 6-month, 12-month visits
Title
Change in Serum Tumor Necrosis Factor (TNF)
Description
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Time Frame
Baseline, 6-month, 12-month visits
Title
Change in Serum Interleukin-17 (IL-17) Concentrations.
Description
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Time Frame
Baseline, 6-month, 12-month visits
Title
Number of Unused Study Drug Sachets.
Description
This will be determined by contacts (twice monthly telephone or at research center visits) of the study coordinator with each subject and responses to three standardized question areas: 1) "Are you having any difficulty, problems or new symptoms with the study medication?" 2) If yes, "What has the problem been?" and 3) "Have you missed any of your study drug doses, and if so how many in the previous 2 week period?" Appropriate notations based on subject responses will be documented in the case report form (CRF). Subjects will be instructed at study entry and reminded via serial contacts to return all of their used and unused drug sachets at each research center visit. Unused and used study drug sachets will be tallied and recorded in the CRF by the study coordinator serially for the entire study.
Time Frame
Every two weeks during the study 12-months
Title
Gastrointestinal Symptom Rating
Description
Study drug tolerance will be assessed by obtaining serial measures of the Gastrointestinal Symptom Rating Scale (GSRS). These will be obtained with in-person interviews at the baseline and month 6 and 12 visits and by telephone contact with all subjects by the study coordinator every 2 weeks. Data will be analyzed within the 5 symptom domains depicting symptoms related to gastric reflux, abdominal pain, indigestion, diarrhea, and constipation.The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. A GSRS total score, the sum of all 5 domains, will also be assessed.
Time Frame
Every two weeks during the study 12-months
Title
Study Retention Rate.
Description
The number of participants who complete all study visits, phone calls, and maintain drug compliance. Retention will be documented via conventional Consolidated Standards of Reporting Trials (CONSORT) criteria and documentation of missed study visits, missed telephone communications and compliance with study drug administration. All data will be maintained in the CRFs.
Time Frame
Up to 12 months
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Females
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willing and able to give written informed consent for participation in the study
Age range 50-65 years
Menopausal status (defined by >1 yr since last menstrual period or follicle stimulating hormone (FSH) level in the postmenopausal range)
Ambulatory
Body mass Index (BMI) must be ≥ 18 and ≤ 32 kg/m2 at screening
Bone mineral density (BMD), expressed as T-scores, must be > - 2.5 in the lumbar spine (L1-L4), the femoral neck, and the total hip, as measured by DEXA
Commitment not to use any products that may influence the study outcome
Ability to understand and comply with the requirements of the study
Exclusion Criteria:
Premenopausal status
History of >1 previous atraumatic bone fractures after age 50
Presence of established osteoporosis (T-score ≤ - 2.5, in the lumbar spine, femoral neck or total hip as measured by screening DEXA)
History of immunological or bone-related disorders including: HIV infection, Type I diabetes mellitus, bone marrow or organ transplantation; Inflammatory bowel disease (ulcerative colitis, Crohn's disease); multiple myeloma; osteomalacia; osteosarcoma; Paget's disease; rheumatoid arthritis; systemic lupus erythematous; parathyroid disorders
Uncontrolled type II diabetes mellitus (HgbA1c ≥ 7% within the last 12 months)
History of bariatric surgery or other forms of malabsorption (including documented celiac disease, or chronic diarrhea)
Alcohol abuse
Clinically significant chronic kidney disease (stage ≥ 2, with total serum creatinine level > 2.5 mg/dL and calculated glomerular filtration rate (GFR) < 60 mL/min by the Modification of Diet in Renal Disease (MDRD equation)
Clinically significant cardiovascular disease (myocardial infarction, cerebral vascular accident or acute congestive heart failure within the previous 12 months
Any malignancies, other than localized skin squamous cell carcinoma, diagnosed within the previous 5 years, or any history of metastatic cancer
History of use of oral supplement products containing probiotic bacteria (more than once per week) within four weeks prior to baseline
Current use (within the past 8 weeks) of any medication with known influences on the immune or skeletal system (e.g. immune modulation therapy, systemic glucocorticoids, systemic steroid hormones
Use of oral or injectable bisphosphonates for more than 1 year within the last 5 years
Current or past use (within 1 year) of Denosumab, Teriparatide, Raloxifene, hormone replacement therapy (HRT), calcitonin, or any other anti-resorptive agent other than bisphosphonates used for the prevention and treatment of osteoporosis
Use of antibiotics during the previous two months or frequent user of antibiotics (>2 courses during the previous 12 months) for any cause
Smoking or use of nicotine-containing products during the last six months
Known hypersensitivity to any of the ingredients in the VSL#3 or the placebo study drug
serum or plasma 25-hydroxyvitamin D [25(OH)D] concentration < 12 ng/mL
uncontrolled thyroid disease (abnormal blood thyroid stimulating hormone (TSH) level within the last 12 months and/or changing dose of thyroid replacement therapy within the last 12 months)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberto Pacifici
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital Clinical Research Network, Emory Clinic, Emory St. Joseph's Hospital, Emory University Hospital (non-CRN)
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women
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