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Investigator terminated trial pursuant to research contract rights.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VSL#3 | Experimental | VSL#3 two active sachets [containing 450x109 colony-forming units (CFU)/sachet], taken daily in a single administration. |
|
| Control | Placebo Comparator | Placebo, no supplemental probiotics. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VSL#3 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 12-month visit. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 12-month visit. |
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Inclusion Criteria:
Exclusion Criteria:
Females
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| Name | Affiliation | Role |
|---|---|---|
| Roberto Pacifici | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University Hospital Clinical Research Network, Emory Clinic, Emory St. Joseph's Hospital, Emory University Hospital (non-CRN) | Atlanta | Georgia | 30322 | United States |
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35 individuals consented to participate. The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm.
Participants were recruited at Emory University Hospital in Atlanta, Georgia, USA. Enrollment began on October 1, 2017 and all study activity stopped on March 23, 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | VSL#3 | Participants randomized to receive two sachets of the VSL#3 probiotic, taken orally daily in a single administration. |
| FG001 | Placebo | Participants randomized to receive two placebo sachets, taken orally daily in a single administration. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm.
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| ID | Title | Description |
|---|---|---|
| BG000 | VSL#3 | Participants randomized to receive two sachets of the VSL#3 probiotic, taken orally daily in a single administration. |
| BG001 | Placebo | Participants randomized to receive two placebo sachets, taken orally daily in a single administration. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline and 12-month visit. |
|
Upon beginning to take the study products, participants were called every other week to monitor for any adverse effects. In addition to twice monthly phone calls, participants were asked to complete Subject Diary Cards to capture adverse events during the course of the trial and up to 1 month following the cessation of the study drug (up to Month 13).
The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | VSL#3 | Participants randomized to receive two sachets of the VSL#3 probiotic, taken orally daily in a single administration. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Roberto Pacifici, MD | Emory University | 404-712-8420 | roberto.pacifici@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 17, 2018 | Feb 18, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015663 | Osteoporosis, Postmenopausal |
| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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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.
| Placebo | Other | Two placebo sachets taken orally daily in a single administration. |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Up to 12 months |
| BG002 | Total | Total of all reporting groups |
|
| Age, Continuous |
| Sex: Female, Male |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. |
| Region of Enrollment | participants |
|
| OG001 |
| Placebo |
Participants randomized to receive two placebo sachets, taken orally daily in a single administration. |
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline and 12-month visit. |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline, 6-month, 12-month visits |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline, 6-month, 12-month visits |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline, 6-month, 12-month visits |
|
|
| Secondary | Change in Serum Osteoprotegrin (OPG) Concentrations. | Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline, 6-month, 12-month visits |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline, 6-month, 12-month visits |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Baseline, 6-month, 12-month visits |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Every two weeks during the study 12-months |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Every two weeks during the study 12-months |
|
|
| Secondary | 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. | The investigational product became the subject of a court judgment upholding false advertising claims concerning the product's similarity to earlier products sold under the same name. Because of questions raised by this ruling, no participants are considered as being assigned to a protocol-defined study arm. | Posted | Up to 12 months |
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Placebo | Participants randomized to receive two placebo sachets, taken orally daily in a single administration. | 0 | 0 | 0 | 0 | 0 | 0 |
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| D008659 |
| Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |