Menopausal OsteoporosisPhase 2ProBoneVSLNCT03165747
Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women
A Phase 2 study testing VSL#3 in people with Menopausal Osteoporosis, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 65 years, women only
- Conditions the study is for
- Menopausal Osteoporosis
- What is being tested?
- VSL#3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2017to 23 Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 19Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University Hospital Clinical Research Network, Emory Clinic, Emory St. Joseph's Hospital, Emory University Hospital (non-CRN)
Atlanta, Georgia, 30322
About this study
Official title: Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women: a Pilot Randomized, Placebo-Controlled Trial
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.
Read the 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.
- Conditions
- Menopausal Osteoporosis
- Being tested
- VSL#3, Placebo
- Keywords
- Probiotics, Menopausal Osteoporosis
- Medical subject headings
- Osteoporosis, Postmenopausal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VSL#3Drug
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.
PlaceboOther
Two placebo sachets taken orally daily in a single administration.
| Study group | Role | What they receive |
|---|---|---|
| VSL#3 | Experimental | VSL#3 two active sachets [containing 450x109 colony-forming units (CFU)/sachet], taken daily in a single administration. Receives: Drug: VSL#3 |
| Control | Placebo comparator | Placebo, no supplemental probiotics. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 12-month visit.
Secondary outcomes (10)
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.
Measured: Baseline and 12-month visit.
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.
Measured: Baseline, 6-month, 12-month visits
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.
Measured: Baseline, 6-month, 12-month visits
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.
Measured: Baseline, 6-month, 12-month visits
Change in Serum Osteoprotegrin (OPG) Concentrations.
Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
Measured: Baseline, 6-month, 12-month visits
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.
Measured: Baseline, 6-month, 12-month visits
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.
Measured: Baseline, 6-month, 12-month visits
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.
Measured: Every two weeks during the study 12-months
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.
Measured: Every two weeks during the study 12-months
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.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2017
- Study start1 Oct 2017
- Primary completion23 Mar 2019
- Study completion23 Mar 2019
Why it stopped: Investigator terminated trial pursuant to research contract rights.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Menopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roberto Pacifici, Emory University
- Investigators
- Roberto Pacifici, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03165747
- Sponsor's protocol ID
- IRB00095798
- Acronym
- ProBoneVSL
- Status last verified
- Mar 2020
- First submitted
- 23 May 2017
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women: a Pilot Randomized, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT03165747
- Acronym / sponsor ID
- ProBoneVSL / IRB00095798
- Conditions
- Menopausal Osteoporosis
- Keywords
- Probiotics, Menopausal Osteoporosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigator terminated trial pursuant to research contract rights.
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 23 Mar 2019 (actual)
- Study completion
- 23 Mar 2019 (actual)
- First posted
- 24 May 2017 (actual)
- Results
- Posted 4 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VSL#3 | Experimental | Drug: VSL#3VSL#3 two active sachets [containing 450x109 colony-forming units (CFU)/sachet], taken daily in a single administration. |
| Control | Placebo comparator | Other: PlaceboPlacebo, no supplemental probiotics. |
Who may qualify
- Ages
- 50 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VSL#38 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. | Drug | VSL#3 |
| PlaceboTwo placebo sachets taken orally daily in a single administration. | Other | Control |
Primary outcome
Change in Bone Mineral Density (BMD) of the Lumbar Spine (L1-L4 Segment) as Measured by Dual Energy X-ray Absorptiometry (DEXA)
Time frame: Baseline and 12-month visit.
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.
10 secondary outcomes
Change in Bone Density of the Non-dominant Hip (Femoral Neck and Total Hip Area) as Measured by DEXA (Dual Energy X-ray Absorptiometry).
Time frame: Baseline and 12-month visit.
Change in Serum Collagen Type 1 Cross-linked C-telopeptide (CTX) Concentrations (a Marker of Bone Resorption).
Time frame: Baseline, 6-month, 12-month visits
Change in Serum Procollagen Type I N Propeptide (PINP) - a Marker of Bone Formation - Concentrations.
Time frame: Baseline, 6-month, 12-month visits
Change in Serum Free Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) Concentrations.
Time frame: Baseline, 6-month, 12-month visits
Change in Serum Osteoprotegrin (OPG) Concentrations.
Time frame: Baseline, 6-month, 12-month visits
Change in Serum Tumor Necrosis Factor (TNF)
Time frame: Baseline, 6-month, 12-month visits
Change in Serum Interleukin-17 (IL-17) Concentrations.
Time frame: Baseline, 6-month, 12-month visits
Number of Unused Study Drug Sachets.
Time frame: Every two weeks during the study 12-months
Gastrointestinal Symptom Rating
Time frame: Every two weeks during the study 12-months
Study Retention Rate.
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roberto Pacifici principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VSL#3 in people with Menopausal Osteoporosis, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Bone Mineral Density (BMD) of the Lumbar Spine (L1-L4 Segment) as Measured by Dual Energy X-ray Absorptiometry (DEXA) (time frame: Baseline and 12-month visit.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.