Exercise in Burn Survivors: Cooling Modalities
Phase: NA
Conditions: Burn Injury
Sponsor: University of Texas Southwestern Medical Center

Title: Exercise in Burn Survivors: Cooling Modalities 
 
NCT Number: NCT04512976 
 
Document Date: May 20, 2024 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
1 
V2Mar2018 
PROTOCOL FORM / RESEARCH DESCRIPTION 
 
If an item does not apply to your research project, indicate that the question is "not applicable” – do not leave sections blank 
 
Click once on the highlighted entry in each box to provide your response.  Click the item number/letter or word, if hyperlinked, 
for detailed instructions for that question.  If your response requires inserting a table, picture, etc, you may need to first delete the 
box that surrounds the answer and then insert your table or other special document. 
 
 
1.  Purpose and objectives.           List the purpose and objectives: 
 
The purpose of this project is to identify modalities to attenuate excessive elevations in skin and internal 
body temperatures during physical activity in well-healed burn survivors. 
 
 
2.  Background. 
• 
Describe past experimental and/or clinical findings leading to the formulation of your study.   
• 
For research involving investigational drugs, describe the previously conducted animal and human studies.   
• 
For research that involves FDA approved drugs or devices, describe the FDA approved uses of this drug/device in 
relation to your protocol.   
• 
Attach a copy of the approved labeling as a product package insert or from the Physician’s Desk Reference.   
You may reference sponsor’s full protocol or grant application (section number and/or title) or if none, ensure background 
includes references. 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
a. 
Background 
Within the United States hundreds of thousands of severely injured burn survivors are presently enduring 
the long-term consequences of their injuries. For example, 3-10 years following a severe burn injury 
fatigue is an “almost universal complaint” and a major barrier in returning to work and performing 
activities of daily living. Notably, we identified that ~75% of well-healed burned survivors have an aerobic 
capacity in the lowest 20th percentile relative to age- and sex-matched normative values; values 
associated with a 3 to 5 fold greater mortality risk 9. Consistent with these values, well-healed burn 
survivors have greater all-cause mortality rates, greater hospitalization days for “circulatory diseases”, 
and suffer from greater incidences of ischemic heart disease, heart failure, diabetes, and 
cerebrovascular disease (including stroke) relative to matched non-burned cohorts. Though the 
mechanisms responsible for these consequences are unknown, similar adverse responses are observed 
in sedentary non-burned individuals. Given our findings that burn survivors are capable of realizing the 
positive cardiovascular and metabolic benefits of physical activity (given sufficient encouragement), a 
critical unanswered question is, “why do burn survivors (as a population) not participate in physical 
activity sufficient to maintain optimal health and to avoid the negative sequelae associated with a 
sedentary lifestyle?” 
 
Burn survivors have severely impaired body temperature regulation, owing to permanent impairments 
in the primary thermoeffectors necessary to dissipate heat, namely profoundly blunted skin blood flow 
and sweating responses in the injured skin. Given that excessive elevations in skin and internal body 
temperatures impair perceptual, behavioral, and performance aspects of physical activity, we propose 
that this heat intolerance is an impediment to an active lifestyle in burn survivors. Thus, identifying 
effective modalities to attenuate the excessive elevations in skin and internal temperatures during 
physical activity in burn survivors will aid in their full rehabilitation by removing a substantial barrier 
(e.g., heat intolerance) to participating in such activities. To that end, a primary objective of the 
proposed work is to identify cooling modalities that are effective in burn survivors, thereby helping 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
2 
V2Mar2018 
these individuals enjoy the rehabilitative and health benefits of physical activity and curtail adverse 
consequences of a sedentary lifestyle. 
 
b. 
Current practice 
N/A  
 
 
3.  Study Design.  
Describe the study design (e.g., single/double blind, parallel, crossover, etc.)  Consider inserting a scheme to visually present the 
study design. 
 
We will conduct a randomized crossover design study. Non-burned control subjects, subjects who 
experienced burns covering ~20% to 40% of their body surface area, and subjects having burns >40% of 
their body surface area will be investigated. In one of the three environmental conditions outlined in Table 
1, subjects will exercise while receiving one of the indicated cooling modalities. 
 
 
 
 
 
 
 
 
Table 2: Procedures and visits 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Informed Consent 
X 
 
 
 
 
Urine Sample 
X 
X 
X 
X 
X 
Body Composition 
(DXA) 
X 
 
 
 
 
Exercise Test 
X 
 
 
 
 
12 lead ECG 
X 
 
 
 
 
Alcohol Intake 
Survey 
X 
 
 
 
 
International 
Physical Activity 
Survey 
X 
 
 
 
 
Screening 
Questionnaire 
X 
 
 
 
 
Heart Rate 
X 
X 
X 
X 
X 
Blood Pressure 
X 
X 
X 
X 
X 
Internal 
Temperature 
 
X 
X 
X 
X 
Skin Temperature 
(including infrared 
imaging) 
 
X 
X 
X 
X 
Skin blood flow 
and sweating 
measures 
 
X 
X 
X 
X 
Blood samples 
 
X 
X 
X 
X 
Table 1: Proposed environmental conditions and cooling modalities. 
Environmental 
Conditions 
Condition  
A 
Condition 
B 
Condition 
C 
Condition 
D 
24 °C; 40% RH 
Control (no fan 
or skin wetting) 
Skin wetting 
only 
Fan only 
Skin wetting 
with a fan 
30 °C; 40% RH 
Control (no fan 
or skin wetting) 
Skin wetting 
only 
Fan only 
Skin wetting 
with a fan 
No higher than 
40 °C; 40% RH 
Control (no fan 
or skin wetting) 
Skin wetting 
only 
Fan only 
Skin wetting 
with a fan 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
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V2Mar2018 
Metabolic Rate & 
ventilation 
 
X 
X 
X 
X 
Perceptual Survey 
 
X 
X 
X 
X 
Echocardiogram 
X 
X 
X 
X 
X 
 
 
4.  Research Plan / Description of the Research Methods:   
4.a.  Provide a comprehensive narrative describing the research methods.   
     1) Provide the order in which tests/procedures will be performed,  
     2) Provide the setting for these events and a description of the methods used to protect privacy during the study.   
     3) Provide the plan for data analysis (include as applicable the sample size calculation) 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
 
The setting for all visits will be the Institute for Exercise and Environmental Medicine. Subjects will be 
recruited from: 1) the UTSW or IEEM volunteer research registry, 2) flyers/advertisements posted/shared 
at major burn centers throughout the United States, 3) info-articles and email blasts disseminated by our 
collaborator, the Phoenix Society, which is the largest burn support group in North America, as well as 
smaller (i.e., regional) burn support groups, 4) database of burned soldiers via our collaboration with the 
US Army, and 5) database of burn survivors maintained at UT Southwestern by the Co-Investigator 
(Karen Kowalske, MD) IRB protocol number: Study00000105. The latter database will be accessed by the 
Study Team to identify burn survivors who meet the inclusion/exclusion criteria outlined in Form C. Those 
individuals will be informed of the study, along with instructions to contact the Study Team should they be 
interested in participating. 
Trials will be conducted in controlled laboratory settings. Burn survivors and non-burned individuals will 
perform bouts of exercise at a given environmental temperature as outlined in Table 1. Subjects will be 
required to perform exercise across all four of the conditions (i.e., Conditions A-D in Table 1) for a given 
environmental temperature. However, a subject will not be required to perform the battery of trials across 
all three environmental temperatures. Within a particular environmental temperature, the order of 
exposure for Conditions A-D will be randomized. Prior to being assigned to an order of cooling modalities 
for any given environmental temperature, we will obtain participant demographics, anthropometrics (body 
mass, height and composition) and aerobic capacity data.  
For a particular environmental chamber trial, baseline data will be collected while resting in a 
thermoneutral environment outside of the environmental chamber. Participants will then enter the 
environmental chamber and be seated while instrumentation is completed. Subjects will then exercise at 
a mild/moderate workload for 60 min.  The assigned cooling modality will be employed throughout the 
exercise bout. The primary assessed variables are the increase in internal and skin temperatures. Upon 
completion of the exercise bout, participants will rest for no more than 60 minutes in the chamber during 
which time we will monitor temperatures and obtain echocardiogram images, then the environmental 
temperature will be reduced and subjects will be de-instrumented. 
 
Data will be digitized upon acquisition, name encrypted, and stored in password protected computer 
folders. Only approved personnel will have access to subject files that will otherwise be locked. Research 
data and medical history will be available to the PI and his staff. Members and staff of the Institutional 
Review Board (IRB) at UT Southwestern Medical Center and Texas Health Presbyterian Hospital may 
review subjects’ records. A representative of these IRBs may contact the subject for information about 
their experience with this research project. The subject may refuse to answer any questions the 
representative of the IRB may ask. All subjects’ information will be kept confidential unless the subject 

Form A 
IRB # 30204 
STU-2020-0334 
 
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V2Mar2018 
gives the researchers permission to share with others or if the investigators are required by law to release 
it. All hard copy documents will be stored behind at least two locked doors/devices and only individuals 
who are involved in this research project can access the files. Information contained in reports or 
publications issued as a result of this research project will be presented in such a way that the subject 
identity will not be revealed. The signed consent form will be kept on file in the subject’s laboratory chart. 
Disclosure of information to third parties will be prohibited.    
Statistical support will be provided by Linda Hynan, Ph.D., Professor in the Department of Clinical 
Sciences, Division of Biostatistics at UT Southwestern Medical Center at Dallas. Descriptive statistics (i.e., 
group characteristics such as age, body mass, BSA burned, physical activity questionnaire data, etc.) will 
be analyzed via one-way analysis of variance to compare the three study groups. Within each 
environmental exposure, the primary evaluation will address an expected interactive effect of group and 
the employed cooling condition (e.g., Conditions A-D as outlined in Table 1) on the magnitude of the 
elevation in internal body temperature to 60 min of exercise. These data will be statistically analyzed via a 
two-factor mixed-effects model repeated measures analysis with main factors of group and the applied 
cooling condition (crossover repeated factor), and their interaction, with subject modeled as a random effect 
and specifying covariance structure, using SAS Proc Mixed. Potential mechanisms contributing to differing 
elevations in internal body temperature (e.g., differences in magnitude of changes in skin temperature and 
skin surface water vapor pressure) as a result of the exercise bouts will be statistically evaluated via the 
same approach. The extent and significance of the expected interactions will be statistically explored post-
hoc with appropriate comparisons derived from the models’ least square means contrasts, applying 
Bonferroni type adjustments for multiple testing.    
We estimated power to detect a 0.5 °C mean difference in the elevation in internal body temperature to 
the exercise bout between groups. This number was obtained from one of our prior studies in which 
similar thermoregulatory responses to exercise in burn survivors were assessed, with a standard 
deviation of the elevation in internal body temperature being ~0.3 °C. Based upon these estimates, 12 
subjects per group for each environmental exposure would provide omnibus power of 0.94 for group 
differences in the elevation in internal body temperature of 0.45 °C at an alpha of 0.05 and power of 0.84, 
using an adjusted alpha of 0.0125 to account for multiple comparison evaluations of the four interventions 
between groups. For the within group comparison, power is >0.9 to detect a difference in the increase in 
internal body temperature of 0.4 °C at an alpha of 0.0125 (power analyses from: NCSS PASS 15). 
Nevertheless, we will enroll 18 subjects per group (9 male and 9 female) for each environmental 
exposure to allow for attrition as well as provide additional power to evaluate any sex-related differences, 
should they become apparent. Randomization within groups for the order of the applied cooling modality 
will be implemented with a Latin square blocking design. 
 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
5 
V2Mar2018 
 
4.b.  List of the study intervention(s) being tested or evaluated under this protocol 
 
N/A -  this study does not test or evaluate an intervention.    Skip to item 4.d. 
# 
Study intervention(s) being tested or evaluated under the protocol 
 
 
 
Add or delete rows as needed 
 
Affiliate 
 
Place a check next to 
institution(s) where 
the  
intervention will be 
performed 
Local Standard 
Practice?  
Indicate whether the 
intervention is 
considered 
acceptable practice 
locally for applicable 
institutions 
1 
Skin cooling (fan and skin wetting) 
☐ UTSW 
☐ Yes 
☐ PHHS 
☐ Yes 
☐CMC 
☐ Yes 
☒THR 
☐ Yes 
☐TSRH 
☐ Yes 
☐ Other: _____ 
☐ Yes 
 
 
4.c.  Risk:Benefit Analysis of study interventions being tested or evaluated under this protocol 
For each study intervention identified in section 6b above, complete a risk:benefit analysis table. 
 
(Two tables are provided, copy & paste additional tables as needed or delete both tables if this study does not test an 
intervention) 
 
 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
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V2Mar2018 
4.c. 
Study Intervention #1 
Cooling Modalities (fan and skin wetting) 
List each group exposed to this 
intervention on a separate line. 
(e.g., experimental, control, Arm A, Arm B, 
etc) 
Or state All Groups/Subjects 
For each group, list the benefits of this intervention.  (Benefits can be directly from 
the intervention or from a monitoring procedure likely to contribute to the subject’s 
well being).  If there are no benefits, state “none”. 
All Groups/Subjects 
None; the research subjects will not directly benefit from the cooling 
modality interventions. 
 
 
If you are requesting a Waiver of Informed Consent, complete the table below. 
 
If you have a consent form, list the reasonably foreseeable risks in the consent form (and do not complete this section).   
 
List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious). 
(include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms) 
Do not delete frequency.  Frequency must be estimated because it will assist you with determining which adverse events will require 
prompt reporting.   
 
Not serious 
Serious  
Likely 
These risks are expected to occur in 
more than 20 out of 100 subjects. 
• 
 
• 
 
 
Not serious 
Serious 
Less likely  
These risks are expected to occur in 5-
20 subjects or less out of 100 subjects. 
• 
 
• 
 
 
 
Serious 
Rare  
These risks are expected to occur in 
less than 5 subjects out of 100  
 
• 
 
 
 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
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V2Mar2018 
 
 
4.d. List ALL other research procedures or components not listed in table 4.b. 
        The combination of Tables 4b and 4d should account for all of the research 
procedures that will take place during this study. 
 
Consider grouping similar procedures under a single component (e.g., blood work, CT = safety 
assessments) 
 
 
 
# 
Research component 
• 
individual 
procedures 
 
example: 
Eligibility Assessments 
• 
History and 
physical 
• 
Questionnaire 
• 
Laboratory tests 
Add or delete rows as needed 
Column A 
Local Standard 
Practice Indicate the 
number of times each 
procedure will be 
performed as stipulated 
in the research plan that 
would be performed if 
the participant were not 
participating in the 
study. 
Column B 
Research Only  
Indicate the number of times 
each procedure will be 
performed solely for research 
purposes (meaning that the 
participant would not undergo 
the same number of 
procedures or would not 
undergo the procedure(s) at 
the same frequency if they 
were not participating in the 
study) 
Column D 
Risks 
If you are requesting a Waiver of Informed 
Consent, complete the table below. 
 
List the reasonably expected risks for each procedure 
or group of procedures under the following categories 
as appropriate: 
• Serious and likely; 
• Serious and less likely; 
• Serious and rare; 
• Not serious and likely; 
• Not serious and less likely 
1 
Screening Assessment 
 
 
 
 
Urine Sample 
0 
1 sample for this screening 
 
 
Body Height 
0 
1 
 
 
Body Mass 
0 
1 sample for this screening 
 
 
Blood Pressure 
0 
Up to 6 for this screening 
 
 
12-lead Electrocardiogram 
0 
1 
 
 
Body Composition via DXA 
0 
1 
 
 
Graded Exercise Test 
0 
1 
 
2 
Exercise Measurements 
 
 
 
 
Environmental Conditions 
0 
Continuously 
 
 
Heart rate via ECG 
0 
Continuously 
 
 
Urine Sample 
0 
1 sample per visit 
 
 
Body Mass 
0 
Up to 4 samples per visit 
 
 
Blood Pressure 
0 
Up to 20 samples per visit 
 
 
Internal temperature 
(temperature sensor pill) 
0 
Continuously 
 
 
Internal temperature (via 
rectal thermometer) 
0 
Continuously 
 
 
Internal Temperature 
(suppository pill) 
0 
Continuously 
 
 
Skin temperature/humidity 
0 
Continuously 
 
 
Skin temperature (infrared 
imaging) 
0 
Up to 6 per visit 
 
 
Local sweat rate 
0 
Continuously 
 
 
Activated sweat gland 
0 
Up to 6 per visit 
 
 
Skin blood flow 
0 
Continuously 
 
 
Peripheral intravenous 
catheter and blood samples 
0 
Up to 4 per visit 
 
 
Cardiac output (gas 
rebreathing) 
0 
Up to 6 per visit 
 
 
Metabolic rate and ventilation 
0 
Up to 8 per visit 
 
 
Perceptual Questionnaires 
0 
Up to 20 per heat-wave 
simulation 
 
 
Echocardiogram 
0 
1 sample per visit 
 
 
 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
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V2Mar2018 
 
5.  Safety Precautions.  (Describe safeguards to address the serious risks listed above.) 
a.  Describe the procedures for protecting against or minimizing any potential risks for each of the more than minimal risk 
research procedures listed above. 
Exercise in the prescribed climate conditions: Internal body temperature will be monitored 
throughout each experiment. The protocol will stop, and the environmental temperature will be 
reduced, in the unlikely occurrence that internal body temperature exceeds 39.5°C or upon any 
indication of adverse cardiovascular or neurological symptoms (e.g., lightheadedness, hypotension, 
hypertension, nausea, etc. Our experiences are that the burn survivors and non-burned control 
subjects tolerate the exercise bout well. Upon completion of each protocol, we will ensure that each 
subject is normothermic and adequately hydrated prior to being permitted to leave the laboratory. 
 
Peripheral intravenous catheter and blood samples: There is a small risk of infection and a still 
smaller risk of a blood clot or breakage of the catheter. The likelihood of these complications is remote 
(less than 1 in 10,000) when the procedure is carried out by trained personnel and proper equipment is 
used, as during this study. There is also a small risk of the catheter perforating the vein or not being 
inserted into a blood vessel. The participant may have discomfort, bleeding, and/or bruising and on 
rare occasions, a person may feel dizzy or faint. 
 
Body composition (DXA): The radiation exposure from this procedure is negligible and is estimated 
to be 0.06 mR, which is equivalent to 1/286th the dose of a standard chest x-ray and less than a day’s 
exposure to natural radiation. 
 
Sweat gland activation with iodine embedded paper: This procedure will not be performed if a 
participant has a known allergy to iodine. Given the very small amount of iodine embedded in the 
paper, even if the participant is unknowingly allergic to iodine, this exposure is unlikely to cause any 
irritation; an exception could be a minor rash if the person is particularly sensitive.   
 
Graded Exercise Test: During exercise stress tests, the risk of having a “heart attack” or even dying 
goes up slightly (less than 1/100,000 tests) relative to moderate intensity exercise. There are no 
additional risks involved with completing the graded exercise test beyond that associated with exercise 
and hard physical exertion. Every precaution will be taken to minimize the risk by closely monitoring 
vital signs (blood pressure, heart rate and rhythm) throughout the exercise. These tests will be stopped 
if signs or symptoms of cardiac ischemia develop, if excessive hypertension or hypotension develop, 
or if arrhythmias occur during exercise. American College of Sports Medicine guidelines will be 
followed regarding physician attendance for graded exercise tests. Additionally, a research nurse will 
be present during the graded exercise test to interpret any danger signs and symptoms. 
 
Internal temperature (temperature sensor pill): See comments above regarding the internal body 
temperature cut-off (39.5 °C) for all trials. This pill should not be taken if the subject weighs less than 
80 pounds, nor should the subject take this pill if they have or have had any gastrointestinal disease or 
surgery. The research nurse will also check each subject’s medical history prior to the pill being 
swallowed. Should a subject have any contraindications in taking the pill, the pill will not be ingested. 
Rather, rectal temperature will be obtained.  
 
Internal temperature (rectal thermometer): If rectal temperature is used, the subject will self-insert a 
small single-use rectal temperature thermometer to a pre-marked depth of 15 cm. The rectal 
thermocouple will not be inserted if they have or previously had inflammatory bowel or colon disease 
and/or rectal or anal surgery. They also may not use the thermometer if they currently have 
hemorrhoids (internal or external), rectal bleeding, diarrhea or fecal impaction in the rectum. Each 

Form A 
IRB # 30204 
STU-2020-0334 
 
STU2020-0334, Crandall, FormA-ResearchProtocol, Mod_9, 12-21-21 
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V2Mar2018 
subject’s medical history will be verified prior to self-insertion of the rectal thermometer by the research 
nurse. 
 
Internal temperature (suppository pill): If a suppository temperature sensing pill is used, with a 
gloved hand the subject will self-insert a lubricated temperature sensor pill (like a suppository) into 
their rectum. This pill will be discharged through normal defecation. This temperature sensing pill will 
not be used if the subject currently has hemorrhoids (internal or external), rectal bleeding, diarrhea or 
fecal impaction in the rectum. Each subject’s medical history will be verified by the research nurse prior 
to self-insertion of this pill.  
 
b.  Where appropriate, discuss provisions for ensuring necessary medical or professional intervention in the event of adverse 
events, or unanticipated problems involving subjects. 
A research nurse will continually monitor the well-being of each subject. In addition, physicians and 
nurses at the Institute for Exercise and Environmental Medicine will assist as needed. All members of 
the research team are (at a minimum) Basic Life Support certified and have successfully completed at 
least two ‘mock’ codes per year. All experiments will take place in a hospital environment with a crash 
cart (inclusive of cardiovascular medications and a defibrillator) located within 100 feet of the 
laboratory.  
 
Though unlikely, should a subject experience signs or symptoms of a possible or ensuing adverse 
event (e.g., hypotension, light headedness, nausea, significant discomfort, etc.) during a particular 
procedure, that procedure will be stopped and the environmental chamber will be cooled. The subject 
will remain in the laboratory until they have fully recovered. Upon screening, participants will be given 
contact information for both a nurse and the principal investigator to contact in case any adverse event 
occurs following discharge from experimental days. 
c.  Will the safeguards be different between/among groups?   
Yes 
 
 
No 
If yes, describe here