The Trimethylamine N-oxide (TMAO)-Reducing Effects of a Pomegranate Supplement Simultaneously Administered With L-carnitine
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- Difference in the area under the curve (AUC) of blood plasma TMAO concentrations after pomegranate extract and microcrystalline cellulose interventions.
研究概览
简要总结
Trimethylamine N-oxide (TMAO) is produced in some individuals whose diets include meat, fish, and dairy.These foods are rich in L-carnitine. L-carnitine is metabolised by the liver and gut microorganisms (bacteria) into TMAO. In the TESSA study, investigators will explore whether pomegranate extract can lower the production of TMAO in healthy men and women. This reduction in TMAO production has been associated with decreasing a person's risk of heart disease.
详细描述
The TESSA study is a 18 day randomised, double-blind, placebo-controlled two-arm crossover pilot study conducted at the NIHR (National Institute for Health and Care Research) Norfolk Clinical Research Facility (CRF) in the Quadram Institute in Norwich. Investigators are seeking men and women over the age of 18 years who habitually consume meat, fish, and/or eggs and are TMAO producers to determine whether pomegranate extract affects L-carnitine metabolism compared to a matched placebo. This study is conducted in two phases. The first phase involves two study visits where investigators will identify and invite TMAO producing individuals to continue to the second phase of this study. Moreover, investigators will ask the participant to complete a food frequency questionnaire. The second phase involves two intervention periods which are separated by a 10 day washout. Each intervention period begins with a run-in followed by three study visits. Investigators will precisely quantify the absorption (blood plasma concentrations over time, pharmacokinetic study) and metabolism of L-carnitine and its products of metabolism which includes TMAO. Additionally, investigators will examine pomegranate metabolism and excretion with timed urine collections and stool samples.
Participants will consume three L-carnitine capsules at the first visit during the first phase. In the second phase, participants will consume L-carnitine capsules with the intervention capsules (pomegranate extract or placebo) for the first intervention period then after the washout period, participants will crossover and consume L-carnitine capsules with the other intervention capsules for the second intervention period. For each intervention period, three L-carnitine capsules with four intervention capsules at the first visit following the run-in. During the second phase starting at the run-in period participants will be asked to follow a standardized, controlled diet which will be low in choline, L-carnitine, and ellagitannins.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double blind masking
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Difference in the area under the curve (AUC) of blood plasma TMAO concentrations after pomegranate extract and microcrystalline cellulose interventions.
时间窗: Day 2,3,4,16,17,and 18
Comparison of AUC of blood plasma TMAO concentrations after L-carnitine with pomegranate extract and after L-carnitine with microcrystalline cellulose interventions.
次要结局
- Change in plasma half-life (t1/2) of L-carnitine and its metabolites(48 hours)
- Changes in gut microbiota composition (indices of diversity and in taxonomic abundances) over study duration(Day 2, 4, 16, and 18.)
- Change in the time to reach peak plasma concentration (Tmax) of L-carnitine and its metabolites(48 hours)
- Difference in L-carnitine and its metabolites concentrations from faecal (stool) collections after pomegranate extract and microcrystalline cellulose interventions.(Day 2, 4, and 18.)
- Change in pomegranate polyphenols and their metabolite concentrations from pooled 24 hour urine collections.(Day 3, 4, 17, and 18.)
- Correlation between plasma TMAO concentration and quantity of L carnitine-rich foods consumed in habitual diets of healthy men and women.(Phase 1 Day 2)
- Treatment effects of gut microbiota composition (indices of diversity and in taxonomic abundances) after pomegranate extract and microcrystalline cellulose interventions.(Day 4 and 18.)
- Changes in area under the curve (AUC) from plasma concentrations of L-carnitine and its metabolites(48 hours)
- Change in peak plasma concentration (Cmax) of L-carnitine and its metabolites(48 hours)
- Change in the area under the curve (AUC) from urine concentrations of L-carnitine and its metabolites(48 hours)
- Difference in bacterial transcripts from faecal (stool) collections after pomegranate extract and microcrystalline cellulose interventions.(Day 2, 4, and 18.)