Impact of Lp299v on Vascular Aging in Healthy Adults
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Brachial Artery Flow Mediated Dilation (FMD%
研究概览
简要总结
Emerging data suggest the gut microbiota regulates multiple mechanisms related to vascular aging, but no intervention targeting the gut microbiota has been tested in older adults without cardiovascular risk factors or cardiovascular disease. Early human data suggest an increase in potentially pathological gut metabolites such as trimethylamine-N-oxide (TMAO) are associated with older age, increased vascular stiffness, increased oxidative stress, and reduced nitric oxide (NO) bioavailability as evidenced by impaired endothelium-dependent vasodilation. Based on this data, the investigators hypothesize that supplementation with Lp299v will reverse human vascular aging in healthy older adults free of known traditional cardiovascular risk factors.
详细描述
Multiple lines of evidence suggest that aging results in significant changes in the composition and metabolism of the gut microbiota that accelerate mechanisms responsible for vascular aging. Recent work established cross-sectional associations between phenotypically older vasculature (with increased vascular stiffness and impaired brachial endothelium-dependent vasodilation) and age-related alterations on the composition of the gut microbiota and metabolites that are derived from microbial metabolism such as TMAO (trimethylamine-N-oxide), nicotinamide, tryptophan, and purines. Animal data also suggests short-chain fatty acids favorably impact endothelium-dependent vasodilation. SCFAs exert a direct anti-inflammatory effect on mononuclear cells and increase glucagon-like protein 1 (GLP-1) production which activates endothelial nitric oxide synthase (eNOS) and increases NO levels. Taken together, these data suggest aging-related changes in the gut microbiota could adversely affect vascular health through multiple mechanisms, even in the absence of concomitant cardiovascular risk factors.
Six weeks of Lp299v supplementation in 36 otherwise healthy smokers reduced systemic inflammation, as evidenced by reductions in leptin (an adipokine that stimulates IL-6 production) and IL-6 levels, reduced monocyte adhesion to endothelial cells, and reduced circulating fibrinogen levels (elevated in the setting of inflammation). In addition, Lp299v supplementation reduced oxidative stress based on reduced urinary F2-isoprostanes and had a modest lowering effect on systolic blood pressure.
The investigators will recruit 20 healthy older adults (10 men, 10 women ages 50 or older) without traditional cardiac risk factors or prevalent cardiovascular disease and randomize subjects into a 6-week, double-blind, randomized, placebo-controlled clinical trial of Lp299v supplementation. Measurements of micro-and macrovascular function, systemic inflammation, and stool microbiota composition will be made.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ages 50-99 years
- •For women: 12 months or more since last menstruation
排除标准
- •Systolic Blood Pressure ≥ 130 mmHg or Diastolic BP ≥ 80mmHg
- •Currently taking pharmacological therapies for hypertension, dyslipidemia, or glucose control
- •Diabetes (type 1 or 2) or glycosylated hemoglobin ≥ 5/7%
- •LDL Cholesterol > 160 mg/dL or Total Cholesterol > 200 mg/dL
- •Cigarette use within 3 years of enrollment
- •Average of > 7500 steps per day as measured during screening period
- •Received probiotics, prebiotics, and/or antibiotics within six weeks of enrollment
- •History of chronic renal insufficiency, liver dysfunction, or cancer besides non-melanoma skin carcinomas or localized prostate cancer requiring systemic treatment within 3 years of enrollment
- •History of inflammatory rheumatic diseases known to increase atherosclerotic cardiovascular risk (e.g. rheumatoid arthritis, systemic lupus erythematosus)
- •Known history of cognitive impairment or inability to follow study procedures
- •GI tract illnesses such as short gut syndrome, inflammatory bowel disease, or an ileostomy
- •Daily alcohol use
研究组 & 干预措施
Lp299v
Subjects will consume 20 billion colony forming units of Lp299v (1 serving of GoodBelly fermented oat drink) once daily for 6 weeks
干预措施: Lactobacillus Plantarum 299v in fermented oat drink (Other)
Heat-killed placebo control
Subjects will consume 1 serving of GoodBelly fermented oat drink that has been treated to heat kill all Lp299v once daily for 6 weeks
干预措施: Heat-Killed Placebo control fermented drink (Other)
结局指标
主要结局
Brachial Artery Flow Mediated Dilation (FMD%
时间窗: 6 weeks
This is a measurement of endothelial function in the brachial artery
次要结局
- Carotid-Femoral Pulse Wave Velocity (cfPWV)(6 weeks)
- Brachial Artery Resting Diameter(6 weeks)
- Nitroglycerin-Mediated Vasodilation of the brachial artery (NMD)(6 weeks)
- Stool microbiota beta diversity(6 weeks)
- Hyperemic Flow Velocity(6 weeks)
- Stool microbiota alpha diversity(6 weeks)
研究者
Michael E. Widlansky
Professor
Medical College of Wisconsin