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 during hyperthermia.

Study Overview

• Status: Recruiting
• Conditions: Hyperthermia; Aging
• Intervention / Treatment: Other: Controlled hyperthermia

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. Comprehensive assessments of gastrointestinal barrier function, microbial translocation and systemic inflammation will be assessed in young and older adults. The expected outcome of this work will re-shape out understanding of the consequences of aging on gastrointestinal barrier function during heat waves.

• Study Type: Observational
• Enrollment (Estimated): 36

Contacts and Locations

• Study Contact: Name: Bonnie Orth, MS; Phone Number: 214-345-4737; Email: BonnieOrth@texashealth.org
• Study Contact Backup: Name: Zachary McKenna, Ph.D.; Phone Number: 214-345-4623; Email: zacharymckenna@texashealth.org

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Texas Health Presbyterian Hospital Dallas
      • Principal Investigator: Craig Crandall, Ph.D.
      • Contact: Zachary McKenna, PhD; Phone Number: 214-345-4623; Email: zacharymckenna@texashealth.org
      • Contact: Courtney Kirby, BS RN; Phone Number: 214-345-6502; Email: courtneyhakes@texashealth.org

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

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
• Chronic fatigue syndrome
• Use of immunosuppressant drugs within last 4 weeks prior to screening
• Diagnosed psychiatric disease
• 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?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Younger participants; Individuals aged 18-39 years	Other: Controlled hyperthermia; Individuals will be exposed to a control trial (no hyperthermia) and a controlled hyperthermia trial.
Older participants; Individuals aged over 65 years	Other: Controlled hyperthermia; Individuals will be exposed to a control trial (no hyperthermia) and a controlled hyperthermia trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal permeability before hyperthermia	In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine.	Day 1: 3-5 hours after ingestion of multiple sugar drink.
Gastrointestinal permeability after hyperthermia	In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine.	Day 2: 3-5 hours after ingestion of multiple sugar drink.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota diversity at baseline	Fecal samples will be used for next-generation sequencing and analyzed for diversity.	Day 1: Control trial
Bacterial species - at baseline	Fecal samples will be used for next-generation sequencing and analyzed for bacterial species.	Day 1: Control trial
Microbial translocation	Venous blood samples will be used for next-generation sequencing and analyzed for bacterial species.	Day 2: Directly before and immediately after the controlled hyperthermia
Systemic inflammation	Venous blood samples will be assessed for systemic pro-inflammatory markers a) tumor necrosis factor alpha, interleukin 6, and soluble cd14 receptor.	Day 2: Directly before and immediately after the controlled hyperthermia
Gastrointestinal blood flow	Gastrointestinal blood flow will be measured by analysing the flow of blood in the superior mesenteric artery using ultrasound	Day 2: Directly before and immediately after the controlled hyperthermia
Skin blood flow	Skin blood flow will be measured using laser doppler flowmetry	Day 2: Before and continuously during controlled hyperthermia

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 (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 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 (Estimated): September 6, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

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