Aging and Gastrointestinal Barrier Function

Impact of Aging on Gastrointestinal Barrier Function During Hyperthermia

The purpose of this study is to assess the gastrointestinal responses of the elderly and younger populations during hyperthermia.

Study Overview

• Status: Completed
• Conditions: Hyperthermia; Aging
• Intervention / Treatment: Other: Hyperthermia Trial; Other: Control Trial

Detailed Description

Heat waves are lethal and cause a disproportionate number of deaths in the elderly relative to any other age group. Although gastrointestinal barrier dysfunction is a primary cause of heat related illness, little is known about the effects of aging on gastrointestinal barrier function during hyperthermia. The central hypothesis of this work is that the elderly exhibit greater gastrointestinal barrier dysfunction during hyperthermia. Participants will complete a control trial where gastrointestinal permeability (without heating) will be assessed in young and older adults. In the experimental trial, controlled hyperthermia will be achieved using a water perfused, tube lined suit. Core body temperature will be raised to a maximum of 2 degrees Celsius above the baseline value, or an absolute temperature of 39.5 degrees Celsius. Core temperature will not be collected during the control trial. Comprehensive assessments of gastrointestinal barrier function and systemic inflammation will be assessed in young and older adults. The expected outcome of this work will re-shape our understanding of the consequences of aging on gastrointestinal barrier function during heat waves.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Health Presbyterian Hospital Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Study Population

The study population will be healthy younger and older individuals identified from the general population.

Description

Inclusion Criteria:

• Healthy male and female individuals
• 18-35 years or 65+ years of age
• Free of any underlying moderate to serious medical conditions

Exclusion Criteria:

• Known heart disease
• Any chronic medical conditions requiring regular medical therapy including cancer, diabetes, uncontrolled hypertension, inflammatory bowel disease, and uncontrolled hypercholestrolmia etc;
• Abnormality detected on routine screening suggestive of provocable ischemia or previously undetected cardiac disease or resting left bundle branch block on screening electrocardiogram.
• Current smokers, as well as individuals who regularly smoked within the past 3 years
• Subject with a body mass index ≥35 kg/m2
• Pregnant
• Use of immunosuppressant drugs within last 4 weeks prior to screening
• Use of antibiotics or antimicrobial medication in last month
• Any previous abdominal surgery
• Use of steroids in last 6 weeks
• Regular use of probiotics in last month
• Use of laxatives or anti-diarrhetic in last month

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Younger participants; Individuals aged 18-39 years.	Other: Hyperthermia Trial; Individuals will be exposed to a controlled hyperthermia trial during "Visit 2" of the protocol.; Other: Control Trial; Individuals will be exposed to a control trial (no hyperthermia) during "Visit 1" of the protocol.
Experimental: Older participants; Individuals aged over 65 years.	Other: Hyperthermia Trial; Individuals will be exposed to a controlled hyperthermia trial during "Visit 2" of the protocol.; Other: Control Trial; Individuals will be exposed to a control trial (no hyperthermia) during "Visit 1" of the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Log Lactulose/Rhamnose Following Control Trial	In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine. The urinary recovery of each ingested sugar (lactulose, sucrose and rhamnose) was determined by multiplying the measured concentration of each sugar by the total volume of urine collected and dividing by the dose administered. Since lactulose is degraded in the colon, we used the ratio urine lactulose to rhamnose (L/R) to determine small intestinal barrier permeability.	"Visit 1": 3-5 hours after ingestion of multiple sugar drink.
Log Lactulose/Rhamnose Following Hyperthermia Trial	In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine. The urinary recovery of each ingested sugar (lactulose, sucrose and rhamnose) was determined by multiplying the measured concentration of each sugar by the total volume of urine collected and dividing by the dose administered. Since lactulose is degraded in the colon, we used the ratio urine lactulose to rhamnose (L/R) to determine small intestinal barrier permeability.	"Visit 2": 3-5 hours after ingestion of multiple sugar drink.
Log Sucrose Following Control Trial	The urinary recovery of sucrose was determined by multiplying the measured concentration of sucrose by the total volume of urine collected and dividing by the dose administered. Sucrose is broken down rapidly in the duodenum, thus we used the urinary excretion of sucrose to assess and gastroduodenal permeability.	"Visit 1": 3-5 hours after ingestion of multiple sugar drink.
Log Sucrose Following Hyperthermia Trial	The urinary recovery of sucrose was determined by multiplying the measured concentration of sucrose by the total volume of urine collected and dividing by the dose administered. Sucrose is broken down rapidly in the duodenum, thus we used the urinary excretion of sucrose to assess and gastroduodenal permeability.	"Visit 2": 3-5 hours after ingestion of multiple sugar drink.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Core Temperature During Hyperthermia Trial	Core temperature was measured using an orally ingestible telemetric pill that was taken no less than 1 hour before the baseline period.	"Visit 2": At 0 minutes and 50-90minutes into the hyperthermia trial.

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Craig G Crandall, Ph.D., University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: April 3, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever
• Other Study ID Numbers: STU-2023-0171

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