INvestigation of the Gut microbiomE and STatin Response (INGEST)

Sony Tuteja2 个研究点分布在 1 个国家目标入组 62 人2020年2月6日

适应症Healthy Volunteers

干预措施Placebo Rosuvastatin

概览

阶段: 4 期
干预措施: Placebo
疾病 / 适应症: Healthy Volunteers
发起方: Sony Tuteja
入组人数: 62
试验地点: 2
主要终点: Change in bacterial abundance
状态: 进行中（未招募）
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

There is evidence that the bacteria that naturally reside in the gut can influence how well we respond to medications. Therefore this study will look at how rosuvastatin, a medication used to lower cholesterol levels, may change the bacteria in the gut. Investigators will also examine how the gut bacteria will affect the ability of rosuvastatin to lower cholesterol levels. There will be 4 study visits over the course of about 16 weeks.The expected duration of the study is 2 years. Investigators plan to enroll 100 healthy volunteers during that time.

详细描述

The gut microbiome plays an important role in the metabolism of xenobiotics and contributes to the variation in drug response. Atorvastatin, simvastatin and rosuvastatin, three of the most commonly prescribed statin medications, also display evidence for modulation by the gut microbiome.The objective of this study is to understand the interaction between the gut microbiome and host drug response to statin therapy using 16S rRNA sequencing, metagenomics sequencing and bile acid metabolomics. Aim 1: To compare changes in the gut microbiome in healthy volunteers randomized to an 8-week intervention with rosuvastatin 10mg daily or placebo. Aim 2: To determine the relationship with gut microbiome, fecal bile acid composition, serum FGF19 levels and the change in plasma LDL-C with rosuvastatin. This is a randomized, placebo controlled trial to investigate the effects of rosuvastatin on the gut microbiome, fecal bile acids and FGF19 levels. Healthy volunteers will be randomized to rosuvastatin 20 mg daily or placebo for eight weeks in a 2:1 ratio. Participants will be blinded to treatment assignment. Stool and blood will be collected at baseline, 8 weeks, and 12 weeks for 16S sequencing, plasma lipid assays, bile acid metabolites and FGF19 assays. A subgroup of participants at the tails of LDL-C response will undergo metagenomics sequencing.

注册库

clinicaltrials.gov

开始日期

2020年2月6日

结束日期

2026年3月1日

最后更新

2个月前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Sony Tuteja

责任方

Sponsor Investigator

主要研究者

Sony Tuteja

Research Assistant Professor of Medicine

University of Pennsylvania

入排标准

入选标准

•Participant is capable of giving informed consent
•Participant is aged 18 to 65 years. The gut microbiome has been shown to change gradually with time, although there is no cut-off in age when this occurs.

排除标准

•Participants with cardiovascular disease such as a history of heart failure (New York Heart Association class II-IV), myocardial infarction, stroke, coronary artery bypass graft, hypertension, and hyperlipidemia as these conditions are associated with altered gut microbiome composition.74 Hypertension is defined as blood pressure greater than 160/110 or on any anti-hypertensive medications. LDL-C \>190 mg/dl or \<100 mg/dl and triglycerides \> 400 mg/dl.
•Participants with a history of cancer.
•Kidney disease (serum creatinine \>1.5 mg/dl).
•Liver dysfunction (alanine aminotransferase \> 2 times the upper limit of normal).
•Diabetes mellitus (DM) - Diabetes itself may affect the gut microbiome although this has not been extensively studied. In addition to a prior diagnosis of diabetes mellitus other than that related to pregnancy, a fasting glucose level of greater than 125mg/dL will be used to exclude participation.
•Clinical diagnosis of hypothyroidism
•History of inflammatory disorders of the intestinal tract (i.e. IBD, celiac sprue).
•Use of antibiotics in the prior 6 months.
•Use of pre-, pro-, or synbiotics.
•Chronic medication use (including over the counter medications and herbal supplements) with the exception of oral contraceptives. Since we are evaluating the impact of rosuvastatin on the gut microbiome we would like to exclude the potential impact of confounding medications.