Evaluating an Amino Acid Based Medical Food w/ Diarrhea in Carcinoid Syndrome & Other NETs

A Phase 2 Study Evaluating a Proprietary Amino Acid Based Medical Food (Enterade®) in Patients With Quality of Life Limiting Diarrhea Due to Carcinoid Syndrome and Other Neuroendocrine Tumors (NET).

Primary Objective:

To assess how an amino acid based medical food (Enterade®) helps maintain the intestine's ability to absorb and retain fluids, leading to a reduction in diarrhea due to Neuroendocrine Tumors (NET) and/or Carcinoid Syndrome. This improvement in the absorption will be assessed in part by evaluating changes in average daily stool frequency from baseline in patients receiving Enterade®. Each subject serves as his or her own control.

Secondary Objectives:

• To assess subject reported health-related quality of life in subjects before and after compound administration.
• To characterize the side effect profile and tolerability of Enterade® as measured by the number of total 8-oz Enterade® bottles consumed throughout the trial, and average drinks per day.
• To evaluate changes in serum electrolytes before and after administration of Eenterade®.
• To assess intravenous fluid requirement and/or hospitalization for dehydration secondary to diarrhea between control observation period and active Enterade® period.
• To evaluate difference in utilization of standard-of-care anti-diarrheal medications between control observation period and Enterade® period.
• To compare subjective feeling of bloating and flatulence before and after administration of Enterade®.
• To evaluate changes in patient weight before and after administration of Enterade®.

Study Overview

• Status: Completed
• Conditions: Diarrhea; Neuroendocrine Tumors; Carcinoid Syndrome; Carcinoid Tumor of GI System
• Intervention / Treatment: Dietary supplement: Amino Acid Based Medical Food/Drink

Detailed Description

This prospective, phase 2 study is to assess how Enterade® will affect patient-reported quality of life and intestinal absorption in patients with Carcinoid Syndrome and Neuroendocrine Tumors. The hypothesis is that Enterade® when combined with standard supportive care will improve patient-reported quality of life and help maintain the small bowel's ability to absorb and retain fluids, possibly leading to a reduction in diarrhea frequency.

• This is a non-randomized, supportive-care study.
• Potentially eligible patients will be screened in the University of Kentucky Markey Cancer Center clinics.
• During the screening visit, immediately after signing informed consent, the participant will be given both flavors of enterade® (original vanilla and refreshing orange) to test tolerability and taste.
• Eligible subjects will be given a stool diary and will be asked to document daily stool output (frequency and consistency of stool), use of anti-diarrheal medication and gastrointestinal discomforts (bloating, cramping).
• All lab and screening tests should be completed within 2 weeks prior to registration/initiation of study.
• The study is broken into 3 distinct segments and will apply to all enrolled participants: Baseline observation (Weeks 1-4), Enterade® administration period (4 weeks), Post-Enterade® Period (4 weeks).
• After relapse of diarrhea is documented or the 4 weeks of post-Enterade® observation are completed (whatever happens first), participants will be given the option to restart Enterade® for 1 additional month.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Markey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cohort 1: Participants must have histopathologically confirmed neuroendocrine tumor with 4 or more bowel movements per day on standard anti-diarrheal regimen (which may or may not include somatostatin analogs and telotristat), AND an elevated serum serotonin or plasma serotonin above the upper limit of normal per reference lab.
• Cohort 2: Participants who have histopathologically confirmed neuroendocrine tumor and have 4 or more bowel movements per day on standard anti-diarrheal regimen (which may or may not include somatostatin analogs and telotristat), but are below the cut-point for serotonin elevation.
• Age equal to or greater than 18 years old.
• ECOG performance status ≤2 (Karnofsky ≥60%)
• Ability to tolerate thin liquids by mouth at the time of enrollment.
• Ability to understand and the willingness to sign a written informed consent document.
• Subject who are willing to take enterade® as instructed will be eligible.

Exclusion Criteria:

• Known allergy to Stevia.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active Clostridium difficile infection or history of Clostridium difficile infection.
• Participants with active clostridium difficile infection will be ineligible for this study.
• Participants with a history of inflammatory bowel disease, irritable bowel syndrome, bariatric surgery and/or Celiac disease.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who have had enterade® within the past 12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NET with carcinoid syndrome; Participants with NET and carcinoid syndrome will be instructed to drink two 8 oz. bottles of Amino Acid Based Medical Food/Drink (Enterade®) per day.	Dietary supplement: Amino Acid Based Medical Food/Drink; Study Compound Enterade® is a medical food drink/beverage composed of a proprietary blend of electrolytes and amino acids.; Other Names: Enterade®
Active Comparator: NET w/o cardinoid syndrome; Participants with NET w/o carcinoid syndrome will be instructed to drink two 8 oz. bottles of Amino Acid Based Medical Food/Drink (Enterade®) per day.	Dietary supplement: Amino Acid Based Medical Food/Drink; Study Compound Enterade® is a medical food drink/beverage composed of a proprietary blend of electrolytes and amino acids.; Other Names: Enterade®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of amino acids in tightening the intestinal barrier and protecting from antigenic translocation by evaluating plasma circulating cytokine levels in peripheral blood sample.	ELISA assays will be used to assess pro-inflammatory cytokines IL-1β, IL-6 and TNFα and serum endotoxin from blood samples collected.	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of increased bacterial translocation and systemic inflammation.	Gut inflammation will be assessed through the analysis of fecal lactoferrin using stool specimens.	56 days

Collaborators and Investigators

• Sponsor: Lowell Anthony, MD
• Collaborators: Entrinsic Bioscience Inc.
• Investigators: Principal Investigator: Lowell Anthony, Lucille P. Markey Cancer Center at University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2018
• Primary Completion (Actual): May 18, 2021
• Study Completion (Actual): May 18, 2021

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Enterade; Medical Food/Drink
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Drug-Related Side Effects and Adverse Reactions; Syndrome; Diarrhea; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neuroendocrine Tumors; Carcinoid Tumor; Malignant Carcinoid Syndrome; Serotonin Syndrome
• Other Study ID Numbers: MCC-18-GI-101-EHS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No