Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women: a Pilot Randomized, Placebo-Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Change in Bone Mineral Density (BMD) of the Lumbar Spine (L1-L4 Segment) as Measured by Dual Energy X-ray Absorptiometry (DEXA)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
- •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
排除标准
- •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)
研究组 & 干预措施
VSL#3
VSL#3 two active sachets [containing 450x109 colony-forming units (CFU)/sachet], taken daily in a single administration.
干预措施: VSL#3 (Drug)
Control
Placebo, no supplemental probiotics.
干预措施: Placebo (Other)
结局指标
主要结局
Change in Bone Mineral Density (BMD) of the Lumbar Spine (L1-L4 Segment) as Measured by Dual Energy X-ray Absorptiometry (DEXA)
时间窗: 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.
次要结局
- Change in Serum Osteoprotegrin (OPG) Concentrations.(Baseline, 6-month, 12-month visits)
- Number of Unused Study Drug Sachets.(Every two weeks during the study 12-months)
- Study Retention Rate.(Up to 12 months)
- 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 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 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 Tumor Necrosis Factor (TNF)(Baseline, 6-month, 12-month visits)
- Change in Serum Interleukin-17 (IL-17) Concentrations.(Baseline, 6-month, 12-month visits)
- Gastrointestinal Symptom Rating(Every two weeks during the study 12-months)
研究者
Roberto Pacifici
Assistant Professor
Emory University