Efficacy of a Gut-microbiota Targeted Nutritional Intervention for Promoting Gut Barrier Integrity During Short-term Exposure to Hypobaric Hypoxia.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Difference in intestinal permeability
研究概览
简要总结
The aim of this randomized, crossover clinical trial is to determine the efficacy of a gut microbiota-targeted nutritional intervention containing a blend of fermentable fibers and polyphenols (FP) for mitigating increases in GI permeability, and decrements in immune function and neuropsychologic performance following rapid ascent to simulated high altitude. Fifteen healthy young adults will participate in each of three study phases that include a 14-day supplementation period in which participants will consume 1 of 2 supplement bars: placebo (PL, will be consumed during 2 phases) and FP supplementation (will be consumed during one phase only). During the final 2-d of each phase, participants will live in a hypobaric chamber under sea level or high altitude conditions.
详细描述
The collection of microbes inhabiting the human gastrointestinal (GI) tract, known as the gut microbiota, is increasingly recognized as a mediator of GI, immunologic, and neuropsychologic responses to various environmental and physiologic stressors. The hypobaric hypoxia characteristic of high altitude environments is a stressor that has recently been associated with increased GI permeability, and which has been shown to cause decrements in immune, neuropsychological and physical function. To what extent modulation of the human gut microbiota can mitigate these responses during high altitude exposure is undetermined. The aim of this randomized, crossover clinical trial is to determine the efficacy of a gut microbiota-targeted nutritional intervention containing a blend of fermentable fibers and polyphenols (FP) for mitigating increases in GI permeability, and decrements in immune function and neuropsychologic performance following rapid ascent to simulated high altitude. Fifteen healthy young adults will participate in each of three study phases in random order. Each phase will include a 14-day supplementation period in which participants will consume 1 of 2 supplement bars: placebo (PL, will be consumed during 2 phases) and FP supplementation (will be consumed during one phase only). During the final 2-d of each phase, participants will live in a hypobaric chamber. During one phase the chamber environment will mimic low-altitude conditions (SHAM). During two phases the chamber environment will mimic the barometric pressure at Pike's Peak CO (460 mmHg; HA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double-blinded
入排标准
- 年龄范围
- 17 Years 至 39 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women aged 18 - 39 years (active duty personnel who are 17 yr of age will also be allowed to participate)
- •In good health
- •Physically active
- •For active duty, passed most recent body composition assessment; for civilians, body mass index (BMI) ≤ 30.0 kg/m
- •Self-reports having a bowel movement at least as frequently as every-other-day
- •Self-reports normal vision (with or without glasses) and hearing
排除标准
- •Born at altitudes greater than 2,100 m (~7,000 feet)
- •Living in areas that are more than 1,200 m (~4,000 feet), or have traveled to areas that are more than 1,200 m for five days or more within the last 2 mo
- •Pregnant, expecting to become pregnant during study, or breastfeeding
- •Any of the following medical conditions:
- •Musculoskeletal injuries that compromise exercise capability
- •Metabolic or cardiovascular abnormalities (e.g., kidney disease, diabetes, cardiovascular disease, etc.)
- •Suspected or known strictures, fistulas, or physiological/mechanical GI obstruction
- •Evidence of apnea or other sleeping disorders
- •Evidence of prior high altitude pulmonary or cerebral edema diagnosis
- •Disease of the GI tract including, but not limited to diverticulitis, inflammatory bowel disease, peptic ulcer disease, Crohn's disease, ulcerative colitis
- •Anemia or Sickle Cell Anemia/Trait
- •Alcoholism or other substance abuse issues
- •History of gastric bezoar
- •Swallowing disorders; severe dysphagia to food or pills
- •Implanted or portable electro-mechanical medical devices
- •Allergy to skin adhesive
- •Past GI surgery
- •Colonoscopy within 3 months of study participation
- •Taking prescription medications other than a contraceptive (unless approved by Medical Office and study PI)
- •Regular use of over-the-counter medications (including antacids, laxatives, stool softeners, and anti-diarrheals) unless approved by Medical Office and study PI
- •Any use of antibiotics, except topical antibiotics, within 3 months of study participation
- •Not willing to refrain from using non-steroidal anti-inflammatory medications (NSAIDs) or antihistamine during the study
- •Not willing to stop consumption of prebiotic- or probiotic-containing supplements (e.g.,VSL#3, PRO-15, etc.), or other dietary supplements at least 2 weeks before and throughout study participation
- •Not willing to stop consumption of probiotic-containing foods (e.g., yogurt, etc.) during study participation.
- •Not willing to refrain from smoking any nicotine product (includes e-cigarettes), vaping, and chewing tobacco during controlled-diet periods.
- •Not willing to abstain from caffeine and alcohol during controlled-diet periods.
- •Allergies, intolerances, unwillingness or inability to eat provided foods and beverages
- •Following vegetarian/vegan diet
- •Unable to regularly sleep for 7-10 hr/night
- •Any previous blood donation, within 8 weeks of the first blood draw of the study, of a volume that when combined with the amount of blood to be collected during the study would exceed 550 mL
结局指标
主要结局
Difference in intestinal permeability
时间窗: Study days 20, 40 and 60
Intestinal permeability measured by the ratio of the urinary excretion of sucralose and erythrirol
次要结局
- Difference in zonulin concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in glucagon-like peptide-2 concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in lipopolysaccharide binding protein concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in glucose concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in change in reaction time(Study days 20, 21, 41, 42, 62, 63)
- Difference in cortisol concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in lactate concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in claudin-3 concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in systemic inflammation(Study days 20, 21, 41, 42, 62, 63)
- Difference in bone specific alkaline phosphatase concentrations(Study days 20, 41, 62)
- Difference in carboxy-terminal collagen crosslinks concentrations(Study days 20, 41, 62)
- Difference in tartrate resistant acid phosphatase concentrations(Study days 20, 41, 62)
- Difference in intestinal inflammation(Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65)
- Difference in procollagen type 1 N-terminal propeptide concentrations(Study days 20, 41, 62)
- Difference in immune cell phenotypes(Study days 21, 42, 63)
- Difference in intestinal fatty acid binding protein concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in S100B concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in osteocalcin concentrations(Study days 20, 41, 62)
- Difference in secretory immunoglobulin A concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in T-cell simulated cytokine production(Study days 21, 42, 63)
- Difference in gastrointestinal symptoms; irritable bowel syndrome(Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9)
- Difference in changes in feeling(Study days 20, 21, 41, 42, 62, 63)
- Difference in gastrointestinal pH(Study days 20, 41, 62)
- Difference in insulin concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in glycerol concentrations(Study days 20, 21, 41, 42, 62, 63)
- Difference in development of acute mountain sickness(Study days 20, 21, 41, 42, 62, 63)
- Difference in gastrointestinal symptoms; quality of life(Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9)
- Difference in appetite(Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9)
- Difference in resting metabolic rate(Study days 7, 21, 42, 63)
- Difference in gastrointestinal transit time(Study days 20, 41, 62)
- Difference in natural killer-cell cytotoxicity(Study days 21, 42, 63)
- Difference in willingness to take risks(Study days 20, 21, 41, 42, 62, 63)
- Difference in physical activity energy expenditure(Study days 20, 21, 41, 42, 62, 63)
- Difference in changes in spatial memory(Study days 20, 21, 41, 42, 62, 63)
- Difference in changes in mood state(Study days 20, 21, 41, 42, 62, 63)
- Difference in changes arousal(Study days 20, 21, 41, 42, 62, 63)
- Difference in risk taking behavior(Study days 7, 20, 21, 41, 42, 62, 63)
- Difference in changes in working memory(Study days 20, 21, 41, 42, 62, 63)
- Difference in change in response inhibition(Study days 20, 21, 41, 42, 62, 63)
- Difference in fecal short chain fatty acids(Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65)
- Difference in changes in spatial working memory(Study days 20, 21, 41, 42, 62, 63)
- Difference in simple visual reaction time(Study days 20, 21, 23, 41, 42, 44, 62, 63, 65)
- Difference in language-based logical reasoning(Study days 20, 21, 23, 41, 42, 44, 62, 63, 65)
- Difference in ambulatory vigilance(48-hours/day during study weeks 0, 2, 3, 5, 6, 8, 9)
- Difference in vigilance(Study days 20, 21, 23, 41, 42, 44, 62, 63, 65)
- Difference in gut microbiota composition(Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65)
- Differences in microRNA concentrations(Study days 20, 21, 41, 42, 62, 63)