Gut Microbiota and Atherosclerosis in ESRD

George Washington University, Washington DC

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Persistent inflammation underpins the accelerated atherosclerosis and increased prevalence of protein-energy wasting in maintenance hemodialysis (MHD) patients. However, the etiology of unprovoked inflammation in MHD patients remains unresolved. The human gut harbors 1014 bacteria, and gut microbial imbalance has been linked to inflammation, insulin resistance and atheroscleroisis. Prebiotic oligofructose enriched inulin (p-inulin) has been shown to restore gut microbial balance, thereby reducing endotoxin generation and inflammation. Pentoxifylline (PTX) blocks cytokine generation in response to endotoxemia at the tissue level, and hence complements the actions of p-inulin. In a two-by-two factorial clinical trial, we will randomize 120 MHD patients to receiv p-inulin/PTX/placebo daily for 12 months. First, we will demonstrate the feasibility of recruitment randomization, and retention of study participants in order to record endpoints in at least 90% of participants. Secondly, we will establish the safety and efficacy of p-inulin and PTX in reducing systemic inflammation. Finally, we propose to evaluate the effect of study intervention on selected exploratory clinical end-points: (a) Progression/regression of atherosclerosis will be determined using phase-sensitive dual inversion recovery magnetic resonance (MR) spectroscopy technique; (b) Alterations in muscle mass and visceral fat mass will be examined by MR imaging of thigh and abdomen; and (c) Changes in presence and severity of protein-energy wasting will be determined according to the International Society of Renal Nutrition and Metabolism criteria. This pilot study will prove the concept, establish feasibility and generate preliminary data to justify the launching of a full-clinical trial.