Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women

NCT03165747 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB00095798
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopausal Osteoporosis

Keywords

Probiotics; Menopausal Osteoporosis

Outcome Measures

Primary Outcomes (1)

• 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.

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).

  Baseline and 12-month visit.

• Change in Serum Collagen Type 1 Cross-linked C-telopeptide (CTX) Concentrations (a Marker of Bone Resorption).

  Baseline, 6-month, 12-month visits

• Change in Serum Procollagen Type I N Propeptide (PINP) - a Marker of Bone Formation - Concentrations.

  Baseline, 6-month, 12-month visits

• Change in Serum Free Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) Concentrations.

  Baseline, 6-month, 12-month visits

• Change in Serum Osteoprotegrin (OPG) Concentrations.

  Baseline, 6-month, 12-month visits

Study Arms (2)

VSL#3

EXPERIMENTAL

VSL#3 two active sachets \[containing 450x109 colony-forming units (CFU)/sachet\], taken daily in a single administration.

Drug: VSL#3

Control

PLACEBO COMPARATOR

Placebo, no supplemental probiotics.

Other: Placebo

Interventions

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.

VSL#3

Placebo OTHER

Two placebo sachets taken orally daily in a single administration.

Control

Eligibility Criteria

• Age: 50 Years - 65 Years
• Gender Eligibility Details: Females
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University Hospital Clinical Research Network, Emory Clinic, Emory St. Joseph's Hospital, Emory University Hospital (non-CRN)

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Roberto Pacifici, MD
• Organization: Emory University

roberto.pacifici@emory.edu

404-712-8420

Study Officials

• Roberto Pacifici

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 24, 2017
• Study Start: October 1, 2017
• Primary Completion: March 23, 2019
• Study Completion: March 23, 2019
• Last Updated: March 4, 2020
• Results First Posted: March 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)