A Pilot Study to Determine Fructose Uptake by Primary Human Colorectal Tumors

This proposed study is designed to investigate the specific uptake of fructose by human colorectal tumors. In this study, subjects with colorectal cancer undergoing surgery will receive an oral sugar solution containing fructose or xylose prior to surgery. The tumor will then be resected, and a portion of the tissue will be used to measure the abundance of fructose and xylose. The study hypothesis is that the tumors will take up fructose sugar but not xylose sugar. A comparison of the sugar uptake between the tumor and normal tissues from the adjacent intestinal epithelium and smooth muscle and the liver will be conducted. This proposal will confirm that human colorectal cancer tumors can directly absorb dietary sugars, which has never been demonstrated.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Tumors
• Intervention / Treatment: Dietary supplement: Cohort 1: HFCS (fructose) fed; Dietary supplement: Cohort 2: D-Xylose (xylose-fed)

Detailed Description

This prospective pilot study is designed to investigate the uptake of dietary fructose and xylose by primary human colon tumors. In this study, the recruited patients with colorectal cancer will receive an oral sugar solution containing either Fructose sugar or Xylose sugar before surgery. The tumor will then be resected and a portion of the tumor, normal intestinal tissue, blood, urine, and liver will be used to quantify fructose and xylose.

• Research question Can primary human tumors take up fructose or xylose?
• A statement of the hypothesis The hypothesis is that fructose, but not xylose, can be directly absorbed and stored by primary human colon tumors.
• Design Prospective, non-randomized, pilot, feasibility, single-center, open-label, phase 1, investigator-initiated study to evaluate the uptake of dietary fructose and xylose by primary human colon tumors with 12 subjects in 2 cohorts: Cohort 1: 6 subjects will consume a sugar solution containing fructose and Cohort 2: 6 subjects will consume a sugar solution containing xylose. Eligible subjects that are scheduled to undergo colorectal resection for cancer treatment will be invited to participate in the study in consecutive order from the practice of colorectal surgeons at the time of their preoperative clinic visit. First, Cohort 1 subjects will be enrolled followed by the Cohort 2 subjects.

N=12 Subjects Cohort 1: Fructose sugar solution =6 Subjects Cohort 2: Xylose sugar solution=6 Subjects

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jujhar Singh; Phone Number: 646-962-2789; Email: jus4018@med.cornell.edu
• Study Contact Backup: Name: Julianna Brouwer, MPH; Phone Number: 6469622789; Email: jub2024@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Contact: Jujhar Singh; Phone Number: 646-962-2789; Email: jus4018@med.cornell.edu
      • Contact: Julianna Brouwer, MPH; Phone Number: 646 -962-2789; Email: jub2024@med.cornell.edu
      • Principal Investigator: Alessio Pigazzi, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects of 18 years of age or older, male, and female
• Subjects with a diagnosis of invasive non-hereditary colonic adenocarcinoma who will be undergoing standard of care (SOC) laparoscopic, robot-assisted, or open surgical resection
• The subject provides informed consent

Exclusion Criteria:

• Subjects with a history of uncontrolled diabetes mellitus (A1C >7.0) Type I and Type 2, will be excluded to avoid potential confounders associated with the consumption of a large bolus of sugar (e.g., hyperglycemia and hyperinsulinemia)
• Inflammatory Bowel Disease (Ulcerative Colitis or Crohn's Disease)
• Patients on steroid medications
• Patients with current infectious disease
• Subjects who do not speak English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: HFCS (fructose-fed); Day Before Surgery between 09:00 pm and 10:00 pm Subjects will prepare the sugar solutions (Fructose-containing solution: 250 mL of water containing 41.25 g of D-Fructose and 33.75 g of D-Glucose) by adding 250 ml water to the sugar powder provided by the study team and drink it between 09:00 pm and 10:00 pm. Subjects will be reminded the day before the surgery to drink the solution.	Dietary supplement: Cohort 1: HFCS (fructose) fed; Day Before Surgery Subjects will prepare the sugar solutions (Fructose-containing solution: 250 mL of water containing 41.25 g of D-Fructose and 33.75 g of D-Glucose) by adding 250 ml water to the sugar powder provided by the study team and drink it between 09:00 pm and 10:00 pm. Samples collected before surgery: Blood sample of 5 ml; Urine Samples 5 ml Day of Surgery The anesthesia and surgical procedure will undergo as per regular care. Samples collection at the time the surgical specimen is removed; Blood sample of 5 ml blood will be obtained from the IV line; Tissue samples2 Tumor tissue samples 5mmx5mmx5mm,2 Intestinal /colon tissue samples 5mmx5mmx5mm2 tissue samples from mesentery tissue 5mmx5mmx5mm; Liver Biopsy - a 3-5 mm liver tissue will be obtained for research.; Urine Samples 5 ml
Experimental: Cohort 2: D-Xylose (xylose-fed); Day Before Surgery between 09:00 pm and 10:00 pm Subjects will prepare the sugar solutions (Xylose-containing solution: 250 mL of water containing 41.25 g of D-Xylose and 33.75g of D-Glucose) by adding 250 ml water to the sugar powder provided by the study team and drink it between 09:00 pm and 10:00 pm. Subjects will be reminded the day before the surgery to drink the solution.	Dietary supplement: Cohort 2: D-Xylose (xylose-fed); Day Before Surgery Subjects will prepare the sugar solutions (Xylose-containing solution: 250 mL of water containing 41.25 g of D-Xylose and 33.75g of D-Glucose) by adding 250 ml water to the sugar powder provided by the study team and drink it between 09:00 pm and 10:00 pm. Samples collected before surgery: Blood sample of 5 ml; Urine Samples 5 ml Day of Surgery The anesthesia and surgical procedure will undergo as per regular care. Samples collection at the time the surgical specimen is removed; Blood sample of 5 ml blood will be obtained from the IV line; Tissue samples2 Tumor tissue samples 5mmx5mmx5mm,2 Intestinal /colon tissue samples 5mmx5mmx5mm2 tissue samples from mesentery tissue 5mmx5mmx5mm; Liver Biopsy - a 3-5 mm liver tissue will be obtained for research.; Urine Samples 5 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The abundance of fructose in tumor extracts	The abundance of fructose in tumor extracts assessed by mass spectrometry in the morning after the consumption of oral sugar solutions.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The abundance of Fructose and [13C]-Fructose in the blood	The abundance of Fructose and [13C]-Fructose in the blood in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
Abundance of Fructose and [13C]-Fructose in the urine	The abundance of Fructose and [13C]-Fructose in the urine in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
Abundance of Fructose and [13C]-Fructose in the liver	The abundance of Fructose and [13C]-Fructose in the liver tissue in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
Abundance of Fructose and [13C]-Fructose in the intestine	The abundance of Fructose and [13C]-Fructose in the intestine tissue in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
Abundance of Fructose and [13C]-Fructose in the mesentery tissues	The abundance of Fructose and [13C]-Fructose in the mesentery tissue in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
The abundance of Xylose and [13C]-Xylose in the blood	The abundance of Xylose and [13C]-Xylose in the blood in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
The abundance of Xylose and [13C]-Xylose in the urine	The abundance of Xylose and [13C]-Xylose in the urine in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
The abundance of Xylose and [13C]-Xylose in the liver	The abundance of Xylose and [13C]-Xylose in the liver tissue in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
The abundance of Xylose and [13C]-Xylose in the intestinal tissue	The abundance of Xylose and [13C]-Xylose in the intestinal tissue in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
The abundance of Xylose and [13C]-Xylose in the mesentery tissues	The abundance of Xylose and [13C]-Xylose in the mesentery tissues in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)
The abundance of Xylose and [13C]-Xylose in the in the tumor	The abundance of Xylose and [13C]-Xylose in the tumor in the morning after the consumption of oral sugar solutions assessed by mass spectrometry.	Morning after the consumption of oral sugar solutions(during surgery at the time of specimen removal)

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Alessio Pigazzi, MD,PhD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2022
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Fructose; D-Xylose; Primary Human Colorectal Tumors
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 21-03023487

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