Randomized Study of enterade® to Reduce Diarrhea in Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation

Abstract

High-dose chemotherapy frequently causes injury to the gastrointestinal mucosa, resulting in diarrhea. The purpose of the current study was to assess the tolerability and efficacy of enterade ® in reducing ≥ grade 2 diarrhea (G2D) in association with high-dose melphalan followed by autologous stem cell transplantation (ASCT). We conducted a prospective, double blinded, multi-center trial in which 114 subjects were randomized to receive enterade ® or placebo twice daily during the transplant hospitalization. Gastrointestinal toxicities (nausea, vomiting, oral mucositis and dysphagia) resulted in poor study compliance in both arms. Among subjects who were able to complete planned therapy (13%), the incidence of G2D was lower for those receiving enterade ® as compared to placebo (16% vs 86%, p<0.03). Twice daily oral administration of enterade ® and placebo following high-dose chemotherapy and ASCT was not feasible due to significant gastrointestinal toxicities. Future explorations of enterade ® should be conducted in populations capable of reasonable oral intake.

A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: “VS002A” trial protocol

“…Net absorption in the diseased intestine was improved by the use of Trioral ® ORS and even further improved by the use of VS002. The greater net absorption with VS002 relative to Trioral ® can be explained at least in part by the additional chloride secretion activity of even very small amounts of glucose present in Trioral ® , which has been demonstrated using chamber 36 Cl and 24 Na flux studies [30,38], and an increase in NHE3 (sodium absorption) and decrease in cystic fibrosis transmembrane conductance regulator (CFTR) (chloride secretion) activity in intestinal tissues incubated in VS002 and measured using western blot analysis [37].…”

“…In a multi-center randomized study within a small subset of subjects who were able to maintain compliance with the study intervention, an exploratory analysis showed significantly less severe diarrhea with Enterade® among patients receiving high-dose chemotherapy [ 36 ]. A retrospective chart review of patients with neuroendocrine tumors shows the potential antidiarrheal activity of Enterade® Advanced Oncology Formula [ 35 ].…”

“…VS002 was provided to > 250 adults treated for diarrhea in Indonesia and the Philippines. The consumption of VS002 was well tolerated by all subjects, with no adverse events [ 43 , 44 ].…”

Nonpharmacological approaches for improving gut resilience to chemotherapy

“…Amino acid-based diets have shown promise in preventing gastrointestinal-related toxicities associated with cancer therapy. The commercial medical food known as enterade, a plant-based amino acid diet, has documented success in reducing gastrointestinal symptoms in recent clinical trials [51,52]. Further, rodent studies have demonstrated an enhancement in the absorptive capacity of the small intestine and an improvement in mucosal barrier integrity with amino acid-based diets [53].…”

Inter-agency perspective: Translating advances in biomarker discovery and medical countermeasures development between terrestrial and space radiation environments

“…The University of Florida, which first created the Gatorade sports drink, also recently developed another nutritional plant-based drink for cancer patients, Enterade. It is a commercially available amino acid-based oral rehydration fluid that has been shown to alleviate GI complications experienced by patients undergoing chemo- and/or radiation therapy ( De Filipp et al, 2021 ). Preclinical studies have also shown that Enterade can reverse radiation-induced injury that leads to a breakdown in GI structure ( Gupta et al, 2020 ), increase weight gain and provide a survival benefit in mice ( Yin et al, 2014 ).…”