Aging, Hyperthermia
Conditions
Brief summary
The purpose of this study is to assess the gastrointestinal responses of the elderly and younger populations during 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. 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.
Interventions
OTHERHyperthermia Trial
Individuals will be exposed to a controlled hyperthermia trial during Visit 2 of the protocol.
OTHERControl Trial
Individuals will be exposed to a control trial (no hyperthermia) during Visit 1 of the protocol.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Log Lactulose/Rhamnose Following Control Trial | Visit 1: 3-5 hours after ingestion of multiple sugar drink. | 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. |
| Log Lactulose/Rhamnose Following Hyperthermia Trial | Visit 2: 3-5 hours after ingestion of multiple sugar drink. | 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. |
| Log Sucrose Following Control Trial | Visit 1: 3-5 hours after ingestion of multiple sugar drink. | 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. |
| Log Sucrose Following Hyperthermia Trial | Visit 2: 3-5 hours after ingestion of multiple sugar drink. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Core Temperature During Hyperthermia Trial | Visit 2: At 0 minutes and 50-90minutes into the hyperthermia trial. | Core temperature was measured using an orally ingestible telemetric pill that was taken no less than 1 hour before the baseline period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Younger Participants Individuals aged 18-39 years
Hyperthermia Trial: Individuals will be exposed to a controlled hyperthermia trial.
Control Trial: Individuals will be exposed to a control trial (no hyperthermia). | 9 |
| Older Participants Individuals aged over 65 years
Hyperthermia Trial: Individuals will be exposed to a controlled hyperthermia trial.
Control Trial: Individuals will be exposed to a control trial (no hyperthermia). | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
| Overall Study | Withdrawn by Primary Investigator | 3 | 0 |
Baseline characteristics
| Characteristic | Younger Participants | Older Participants | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 9 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 0 Participants | 9 Participants |
| Age, Continuous | 32 years STANDARD_DEVIATION 3 | 72 years STANDARD_DEVIATION 3 | 52 years STANDARD_DEVIATION 21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 9 Participants | 16 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 18 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 9 | 0 / 11 | 0 / 9 |
| other Total, other adverse events | 0 / 12 | 1 / 9 | 0 / 11 | 0 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 9 | 0 / 11 | 0 / 9 |
Outcome results
Primary
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.
Time frame: Visit 1: 3-5 hours after ingestion of multiple sugar drink.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Participants | Log Lactulose/Rhamnose Following Control Trial | 0.97 Ratio | Standard Deviation 0.39 |
| Older Participants | Log Lactulose/Rhamnose Following Control Trial | 0.79 Ratio | Standard Deviation 0.3 |
Primary
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.
Time frame: Visit 2: 3-5 hours after ingestion of multiple sugar drink.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Participants | Log Lactulose/Rhamnose Following Hyperthermia Trial | 1.22 Ratio | Standard Deviation 0.32 |
| Older Participants | Log Lactulose/Rhamnose Following Hyperthermia Trial | 1.21 Ratio | Standard Deviation 0.29 |
Primary
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.
Time frame: Visit 1: 3-5 hours after ingestion of multiple sugar drink.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Participants | Log Sucrose Following Control Trial | 2.68 log(ng/mL) | Standard Deviation 1.11 |
| Older Participants | Log Sucrose Following Control Trial | 1.74 log(ng/mL) | Standard Deviation 1.66 |
Primary
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.
Time frame: Visit 2: 3-5 hours after ingestion of multiple sugar drink.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Participants | Log Sucrose Following Hyperthermia Trial | 2.83 log(ng/mL) | Standard Deviation 1.1 |
| Older Participants | Log Sucrose Following Hyperthermia Trial | 3.44 log(ng/mL) | Standard Deviation 0.5 |
Secondary
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.
Time frame: Visit 2: At 0 minutes and 50-90minutes into the hyperthermia trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Participants | Change in Core Temperature During Hyperthermia Trial | 2.01 °C | Standard Deviation 0.14 |
| Older Participants | Change in Core Temperature During Hyperthermia Trial | 1.95 °C | Standard Deviation 0.23 |