Development of a Novel Cooling Vest to Prevent Heat-Induced Thermoregulatory Dysfunction in Persons With Spinal Cord Injury
Phase: NA
Conditions: Spinal Cord Injuries
Sponsor: VA Office of Research and Development

Development of a Novel Cooling Vest to Prevent Heat-Induced Thermoregulatory Dysfunction in
Persons with Spinal Cord Injury
NCT05441449
Most Recent Update / Human Subjects Protection Review Board Approval: 08/14/2023 

PART II 
RESEARCH PROPOSAL 
1. SPECIFIC AIMS. 
Problem Statement: Loss of supraspinal control of autonomic pathways interrupts homeostasis of 
multiple organ systems including thermoregulation. Thermoregulatory mechanisms are dysfunctional 
due to interrupted sympathetic pathways for hypothalamic control of vasomotor and sudomotor function 
and motor/sensory pathways for shivering and thermal sensation. During exposure to warm seasonal 
temperatures, dysregulation of heat dissipating mechanisms (vasodilation and sweating) allows core 
body temperature (Tcore) to rise in persons with SCI rather than remaining stable and tightly regulated 
(~37±0.6°C), as occurs in able-bodied (AB) persons. We have reported in persons with higher lesions 
(SCI >T6: Hi-SCI), that even limited exposure (1-2 hours) to typical summer temperatures (35°C) can 
result in Tcore rising to values approaching hyperthermia (≥38°C). Mild hyperthermia causes physical 
discomfort and can impair cognition. Unchecked, hyperthermia can progress to heat exhaustion and 
heat stroke causing seizures, loss of consciousness, and potentially death, as occurred in vulnerable 
residents of the Pacific Northwest during a heat wave in late June 2021.  
Current medical advice for those with SCI is to avoid direct sunlight, dress sparingly, drink plenty of 
fluids, and stay indoors on hot, humid days. Despite heeding this advice, persons with SCI frequently 
find themselves in hot environments for prolonged periods during social, religious, or work functions. 
During these conditions, there is rapid progression to feeling “overheated” and an increased risk for 
heat-related illness. Warm seasonal temperatures limit perceived comfort, performance of activities, 
and participation in societal functions to a greater extent in persons with cervical injury (tetraplegia) than 
in AB controls. Identifying a safe, non-invasive, efficacious bioengineering intervention to restore 
thermoregulatory function during heat exposure has the potential to minimize the negative impact of 
heat on activities, participation, and quality of life (QOL) in Veterans with SCI. If efficacious, other 
Veteran populations adversely affected by heat exposure may also benefit from this intervention.    
Goals: This pilot study will develop and test a self-regulating cooling vest for Veterans with SCI that can 
utilize both conductive and evaporative methods to dissipate body heat as a proof-of-concept to prevent 
an excessive rise in Tcore and thermal discomfort during controlled exposure to a warm environment. 
An initial prototype of the vest has already been developed in collaboration with Dr. Hao Su, a 
bioengineer. A service contract has been established with Picasso Intelligence L.L.C. to further develop 
our initial prototype, under the leadership of Dr. Hao Su, prior to human subject testing. If this study is 
successful, we will collaborate with the Human Engineering Research Laboratory to make the vest 
appropriate for home testing to determine its effectiveness in improving societal participation and QOL 
in Veterans with SCI during warmer seasons or when residing in or traveling to hot climate zones. If 
effective, we are confident that HERL, with the assist of the VA’s Technology Transfer Program, can 
bring this intervention to the commercial market.  
Primary Objective (Safety): To complete development of the 2nd prototype of the cooling vest and 
determine its safety. After satisfying bench testing criteria, AB participants will wear the wet cooling vest 
at maximal settings for 2 hours in the seated position in a warm thermal chamber (35°C), to determine: 
(1) minimum skin temperatures beneath the cooling vest and (2) subjective comfort of the cooling vest.  
Primary Hypotheses: (1) Skin temperatures beneath the vest will be ≥20°C to protect against cold 
injury. (2) AB participants will report a thermal sensation (TS) no less than “cool” on a validated 9-point 
thermal sensation scale. If during testing, a skin temperature of <20°C is measured or a TS < “cool”, or 
“cold spots” are reported, vest development will continue to ensure that the prototype is safe for testing 
in persons with SCI. Once safety criteria for the cooling vest are met in AB subjects, efficacy testing will 
be performed in persons with SCI who will wear the cooling vest during a controlled warm challenge.  
Secondary Objective (Efficacy in SCI): To determine the efficacy of the wet cooling vest to maintain 
Tcore (within 0.3°C) in participants with Hi-SCI when exposed to 2 hours of a warm environment. Using 
a repeated measures design, participants with Hi-SCI will wear the wet vest (experimental condition) or 
no vest (control condition) in a warm thermal chamber (35°C) for up to 2 hours in the seated position, to 
determine: (1) change in Tcore and (2) perception of heat and thermal comfort.  
Secondary Hypotheses: In our previous investigation of heat exposure, 65% of persons with Hi-SCI 
had increases of >0.5°C in Tcore (mean increase 0.6±0.3°C) while wearing only shorts. We expect that 

wearing a cooling vest during the same heat exposure, will significantly increase heat dissipation and, 
thus, enhance maintenance of Tcore and thermal comfort.  We hypothesize that during a controlled 
warm exposure (35°C), participants with Hi-SCI wearing the wet cooling vest compared to the same 
participants not wearing a vest: 1) 65% will have a significantly reduced elevation in Tcore (≤0.3°C), and 
2) a greater percentage of participants will report increased thermal comfort (decreased perception of 
feeling “hot”, “very hot”, or “uncomfortable”). 
 
2. BRIEF REVIEW OF RESULTS OF OTHERS AND CURRENT STATE OF KNOWLEDGE 
Background  
The interruption of autonomic pathways after spinal cord injury (SCI) causes dysregulation of multiple 
organ systems, including thermoregulation.1-4  The consequences of an impaired ability to maintain core 
body temperature (Tcore) may be more subtle than the limitations in activities and mobility caused by 
muscle paralysis due to interrupted motor pathways. Thermodysregulation negatively impacts health, 
personal comfort, and the willingness to participate in functions outside the home.5,6 The prevalence of 
thermodysregulation in persons with SCI has not been reported, but it is related to the integrity of 
sympathetic pathways for vasomotor and sudomotor function and motor/sensory neurological level of 
injury (NLI) for shivering and sensation.3,7 The ability to redistribute blood between central and 
peripheral compartments is impaired the most in persons with tetraplegia (NLI ≥ C8) and high 
paraplegia (NLI ≥T6) due to dysfunctional vasomotor control of central (splanchnic) and peripheral 
(lower extremity) vascular beds, resulting in orthostatic hypotension, as well as autonomic dysreflexia 
due to vascular dysregulation.8-10  
Thermoregulation in Warm Conditions in Able-Bodied (AB) Persons  
Thermoregulation is a precisely controlled homeostatic function, which maintains Tcore within a narrow 
range (37.0±0.6°C) despite a wide range of environmental temperature challenges.11-14 Effective 
thermoregulation depends on the integrity of afferent thermal sensory information, from cutaneous and 
deep thermal receptors, for cortical awareness and initiation of biobehavioral responses (i.e., add or 
remove clothing) and for preoptic hypothalamic processing for appropriate modulation of efferent 
thermoregulatory responses.15-17 Upon recognition of excessive heat storage, from either warm ambient 
conditions or physical activity, the hypothalamus rapidly orchestrates sympathetic-mediated responses 
of vasodilation and sweating to dissipate heat to maintain Tcore within the range of normothermia as 
well as perceived thermal comfort.16,18,19  
Thermoregulation in Warm Conditions after SCI 
In persons with SCI, the interruption of sympathetic pathways limits central regulation of vasodilation 
and sweating for increasing heat loss20,21 and vasoconstriction for decreasing heat loss.2,22 Motor 
pathway interruption, identified by the International Standards for Neurological Classification of Spinal 
Cord Injury (ISNCSCI),23,24 limits involuntary shivering for thermogenesis, as well as the ability to move 
to more temperate environments. Interruption of sensory pathways, also identified by the ISNCSCI, 
impairs awareness of warm or cool ambient conditions, delaying biobehavioral responses (i.e., adding 
or removing clothing) and the ability of the hypothalamus to rapidly orchestrate an effective response. 
As a result, Tcore varies directly with ambient conditions and is frequently outside the optimal range of 
normothermia.3 This dysfunction is more prevalent in persons with SCI above T6 (Hi-SCI) because 
control of vasomotor and sudomotor function has been de-centralized in greater than 60% of the body’s 
surface area and the availability of skeletal muscle for shivering and mobility is limited due to paralysis 
below the neurologic level of lesion (NLI).2,3,22,25 When in warmer environments or during warmer 
seasons, the limited ability to dissipate heat from ambient temperature exposure or generated by 
physical activity results in a predominantly unregulated rise in Tcore and an increased vulnerability to 
hyperthermia (Tcore ≥38°C).3,26,27 Hyperthermia can affect central nervous system function, causing 
impaired cognitive performance, consciousness, blurry vision, nausea, and dizziness.13,28,29  If 
unchecked, hyperthermia can lead to heat stroke, causing loss of consciousness, permanent central 
nervous system damage, and progress to multiple organ system failure and death.29,30 From 2004 to 
2018, a total of 10,527 deaths in the United States resulted from heat exposure.31 The dangers of 

prolonged heat exposure in vulnerable persons were demonstrated by a heat wave that occurred in 
June 2021 in the Pacific Northwest.32-34  
Dysfunctional thermoregulation after SCI also affects quality of life (QOL). Heinemann et al. assessed 
the influence of environmental factors that were perceived as barriers and affected health-related QOL 
in persons disabled from neurological injuries;5 570 participants who suffered a stroke, traumatic brain 
injury (TBI), or SCI (SCI: n=193) rated the difficulty of 18 perceived barriers in home, outdoor, and 
community settings. “Feeling too hot or cold outdoors” was the most frequently reported barrier of the 
18 items, while “feeling hot or cold at home” was the fourth most common barrier. “Feeling too hot or 
cold in stores” was eighth most common barrier.  
When participating in social, religious, or work functions during warmer seasons, persons with SCI 
frequently find themselves in hot environments for prolonged periods, rapidly progressing from feeling 
comfortably warm to feeling “overheated” and uncomfortable and at increased risk for heat-related 
illness. However, interventions addressing thermodysregulation during heat exposure in persons with 
SCI are limited. Exploration of a safe, efficacious bioengineering intervention that has the potential to 
minimize the adverse effects of prolonged heat exposure and its negative impact on participation and 
QOL in Veterans with SCI should be a priority. If efficacious, other vunerable Veteran populations 
adversely affected by heat exposure, e.g., persons with 3rd degree burns, MS, and aged ≥ 70 years of 
age, may also benefit from this intervention,  
Cooling Interventions to Decrease the Risk of Hyperthermia in Able-Bodied (AB) Persons  
Studies in athletes to reduce heat-related illness, increase performance, and control the rise in Tcore 
during exercise in warm ambient conditions have utilized cooling vests, cold water immersion, ice slurry 
ingestion, cooling packs, and facial wind and water sprays.35,36  Investigators have used cooling prior to 
heat exposure (pre-cooling) to increase heat storage capacity and/or during heat exposure (per-cooling) 
to limit heat accumulation.36,37 The cooling vest was found to be most effective during per-cooling due to 
its ability to cover a large surface area of the body and its practicality. Combining its use to both before 
and during exercise afforded the greatest cooling effect.35,38,39 
Cooling Interventions to Decrease the Risk of Hyperthermia in Persons with SCI 
Cooling interventions explored in persons with SCI have included hand and foot cooling, water sprays 
(spray-bottles), and cooling garments (vests, hats, neckbands) primarily during exercise conditions and 
with varying results.40-47 An aluminum back plate on a wheelchair cooled by Peltier transformers was 
developed, but only tested in 5 AB subjects during heat exposure.48 The most promising of these 
interventions seems to be the ice vest and water spray on exposed skin, which, when used either 
before or during exercise in persons with tetraplegia, resulted in Tcore being significantly lower 
compared to the control condition (exercise with no vest or no water spray).44,45 Bongers et al. studied 
use of a cooling vest in persons with low paraplegia during exercise in temperate ambient conditions.46 
They found that the vest improved comfort, lowered skin temperatures, and improved core/skin thermal 
gradient, but did not prevent the increase in Tcore. However, persons with low paraplegia have greater 
thermoregulatory capacity than those with Hi-SCI and the vest may have had a greater effect in persons 
with Hi-SCI during warmer conditions (greater heat load), as evidenced by Trbovich et al. using water 
spray.27,49  Webborn et al. compared the use of an ice vest in athletes with tetraplegia during exercise in 
warm conditions; the vest, either before (20 minutes prior) or during exercise, attenuated the rise in 
Tcore and improved comfort compared to exercise with no vest.45  
However, when used outdoors and for longer periods (e.g., outdoor summer travel, social events), there 
are disadvantages of using a passive ice vest (i.e., replenishing the ice in the vest and the necessity of 
carrying ice). Similar disadvantages exist with water spray (i.e., having someone assist with spraying 
and replenishing the water for the spray). The feedback-controlled “smart” cooling vest does not need 
refilling because it continually cools and recirculates the cooled water for improved heat conduction, its 
temperature can be controlled, and once wet, the material of the vest will continue to provide 
evaporative heat loss for 3-4 hours. 
 
3. PROCEDURES, METHODS AND EXPERIMENTAL DESIGN. 

Research Design: An exploratory protocol with two phases (AB safety; SCI safety and efficacy) will be 
performed.  In Phase 1, because those with Hi-SCI potentially have impaired or absent skin 
temperature sensation, AB participants will wear the wet “smart” cooling vest to determine its safety. 
Phase 2 will be performed for efficacy in a single group of persons with Hi-SCI in a prospective, 
repeated measures design with two conditions (experimental: wet vest, control: no vest) administered in 
random order. The objective of Phase 2 is to determine if persons with Hi-SCI dissipate body heat more 
effectively in the wet vest condition compared to the no vest condition as evidenced by a smaller rise in 
Tcore, a decreased perception of heat, and increased thermal comfort. We expect a mean increase in 
Tcore of 0.6±0.3°C and a perception of feeling “hot or very hot” in the no vest condition, as evidenced in 
two of our prior studies with identical challenges.50,51  
Participants: Ten participants with high-level SCI (C4-T2, AIS A & B) and 5 AB participants matched for 
age (±5 years) and gender will be recruited for study participation.  
Participant Recruitment: Patients referred by their physician following routine physical examinations will 
be approached for potential study enrollment. Physicians will be informed of the inclusion and exclusion 
criteria and will be able to assure us that the patient is an appropriate study participant and that he/she 
is willing to speak with the study coordinators. 
1. Veterans with SCI responding to IRB-approved articles in lay publications and advertisements.  
2. Veterans with an ongoing relationship with our center (Metabolic, Pulmonary, or GI SCI clinics).  
Inclusion Criteria:  
1. 18-68 years of age 
2. SCI >1 year in duration  
3. Level of SCI C4-T2, AIS A & B 
4. Gender and age-matched (±5 years) AB controls 
5. Euhydration (participants will be instructed to avoid caffeine and alcohol, maintain normal salt and 
water intake and avoid strenuous exercise for 24 hours prior to study). 
Exclusion Criteria:  
1. known cardiovascular, kidney or untreated thyroid disease  
2. traumatic brain injury (mod-severe) 
3. diabetes mellitus  
4. acute illness or infection  
5. broken, inflamed, or otherwise fragile skin  
6. pregnancy  
7. BMI >30 kg/m2 
8. smoking  
 
Methods:  On 3 separate days (Phases 1 & 2), participants will arrive in the laboratory between 8:00-
11:00 AM.  
Preparation for Study Visits: Participants will be instructed to avoid caffeine and alcohol, maintain 
normal salt and water intake, and avoid strenuous exercise for 24 hours prior to study on each visit. 
Participants will wear a T-shirt and shorts during all visits to maximize skin exposure to the warm 
temperature. The T-shirt will also prevent the cooling vest from directly touching the skin. Each 
participant will be instructed to eat a light meal (plain bagel or 2 pieces of toast) 2 hours prior to their 
visit. Participants will be asked to empty their bladders prior to the study visit and again upon arrival, if 
necessary.  
Instrumentation: (For all participants) After obtaining informed consent, participants will be instrumented 
in a thermoneutral room (25°C) and in their wheelchair (Hi-SCI) or a provided wheelchair for AB 
controls. Participants will remain seated and relatively still but will be instructed to use their pressure 
relief seat cushion (e.g., Roho) and maintain their usual pressure relief schedule (e.g., weight shifting 
every 15 minutes). Laser Doppler flowmetry (LDF) will be used to measure changes in microvascular 
perfusion rate by placing a Doppler probe on the skin of the ventral forearm and calf bilaterally as an 
index of vascular sympathetic withdrawal. Changes in skin blood flow will assessed from calculations of 
cutaneous vascular conductance (CVC = LDF/MAP), a more accurate measure of change in skin blood 
flow.52,53 An automated blood pressure cuff will be placed above the elbow to measure brachial blood 
pressure (BP) and heart rate (HR).  Sweat rate (SR) will be measured by the Quantitative Sweat 
Measurement System (WR Medical Electronics, Stillwater, MN) with capsules secured to 4 sites: left 

upper arm, left forearm, left mid-thigh, and left midcalf (C5, T1, L3, and L5 dermatomes, respectively). A 
pulse oximeter will be placed on the second digit to detect blood oxygen saturation. An infrared ear 
thermometer will be used to assess tympanic temperature. 
For AB participants (Visit 1): Skin thermocouples will be secured at 12 sites on the ventral and dorsal 
torso (mid-clavicular line from T3 to T10 dermatomes, bilaterally) for collection of skin temperatures 
(Tsk). 
For participants with Hi-SCI (Visits 2 & 3): Participants with Hi-SCI will be asked to empty their bladders 
to minimize risk of AD during the heat stress protocols (wet vest, no vest). Skin thermocouples will be 
secured at 14 sites, 10 skin thermocouples on the ventral and dorsal torso (five on each side) and 4 
additional thermocouples on both hands and feet (2 on each side) for distal skin temperatures as an 
indirect index of sympathetic vasomotor regulation.55 A disposable forehead skin temperature sensor 
(Bair HuggerTM Spot OnTM Temperature Monitoring System, 3M, Maplewood, Minnesota) will be placed 
on the orbital bone, above the eyebrow, on whatever side is most comfortable for the participant in 
order to measure core temperature (Tcore). 
Baseline Collection (BL): (for all 3 Visits) At the end of the instrumentation period (~30 minutes) at 25°C 
while seated and wearing only shorts and a standard T-shirt, a baseline (BL) collection of the following 
parameters will be performed for 15 minutes. Tcore (in persons with Hi-SCI only) and Tsk will be 
measured continuously. Subjective ratings of thermal sensation, assessed on a 9-point scale (TS) and 
general thermal comfort on a 6-point scale (TC).56 HR, BP, blood oxygen saturation, tympanic 
temperature and 5 minutes of LDF will be measured at 10-minute intervals. BP will be assessed 
immediately pre and post each LDF interval for calculation of CVC.57,58 SR will be measured for 15 
minutes continuously. 
1. Thermal Challenge for Safety and Comfort Study (Phase 1; 1 visit, AB participants only): AB 
participants will be fitted with an appropriately sized cooling vest while seated in a wheelchair at the end 
of BL. Participants will be transferred into a pre-heated (35°C, 35% relative humidity) thermal chamber 
for 2 hours with the wet cooling vest on full power. Skin temperatures will be continuously measured at 
multiple sites under the vest. TC and TS will be assessed every 10 minutes. Participants will be queried 
if they feel any areas of cold-related discomfort or numbness (cold spots), or any other feelings of 
discomfort from the vest. LDF will be measured as above, but at 20-minute intervals. SR will be 
measured for 15 minutes every 30 minutes (4 times). HR, BP, blood oxygen saturation and tympanic 
temperature will be assessed at 10-minute intervals. Determinants of success for Phase 1: 1) Skin 
thermocouple temperatures maintained ≥20 °C, and 2) subjective ratings of TS not less than “cool” (i.e., 
not “cold” or “very cold”) on the 9-point TS scale. 
2. Thermal Challenge with Wet Cooling Vest vs. No Vest (Phase 2; 2 visits, participants with Hi-SCI 
only): After 15 minutes of baseline data collection in a thermoneutral environment (25°C), participants 
with HI-SCI will be fitted with an appropriately sized cooling wet vest or will wear no vest (in random 
order). To provide evaporative heat loss, the vest material will be saturated with water using a spray 
bottle. Participants will then be transferred into a warm (35°C, 35% relative humidity) thermal chamber 
for up to 2 hours. Tcore (Bair HuggerTM Spot OnTM forehead skin sensor ) and Tsk (thermocouples at 
multiple sites under the vest and on hands and feet) will be measured continuously; subjective TS and 
TC will be measured at 10-minute intervals; LDF will be measured as above (for CVC) at 20-minute 
intervals. SR will be measured for 15 minutes every 30 minutes (4 times). HR, BP, blood oxygen 
saturation, and tympanic temperature will be measured at 10-minute intervals for vital signs’ 
information. Participants will be queried if they have any feelings of discomfort. If the participant’s Tsk 
underneath the vest falls below 20°C, or Tcore rises to 38°C, and/or the participant requests study 
termination because of discomfort, the vest will be removed, the heat challenge will be immediately 
terminated, and the participant will be transferred to a cool environment, covered with cool blankets, as 
appropriate, and provided cold liquids. The study physician will be directly responsible for subjects’ 
medical safety during study protocols. Subjects’ Tcore, HR and BP, will be monitored at frequent 
intervals. Symptoms suggestive of AD or hyperthermia will be assessed every 10 minutes. The study 
physician will be notified immediately of any symptoms or signs of concern. Subjects will be medically 
evaluated promptly, and the study terminated if any safety issues arise. Subjects will be monitored for at 
least 30 minutes of recovery to ensure Tcore returns to within 1% of BL value. 

Determinants of Efficacy Failure or Success for Phase 2: 65% of participants in the wet vest 
condition will have a significantly reduced elevation in Tcore (≤0.3°C), and 2) a greater percentage will 
report increased thermal comfort (decreased perception of feeling “hot”, “very hot”, or “uncomfortable”) 
compared to the expected increase in Tcore of 0.6°C and reported thermal comfort in the no vest 
condition. 
Outcome Variables: Phase 1: Skin thermocouple temperatures, ratings of thermal comfort and sensation, 
cold spots, and any reported physical discomfort from the vest.  Phase 2: The primary endpoint will be 
the magnitude and rapidity of the rise in Tcore upon exposure to a warm environment. The perception of 
thermal comfort and sensation of heat will be obtained as secondary endpoints.  
Procedures: Thermoregulatory Measurement Procedures: The following measurements will be 
obtained during BL and Thermal Challenge 
for all visits (Table 1). Tcore: will be 
monitored by a disposable forehead skin 
temperature sensor (Bair HuggerTM Spot 
OnTM Temperature Monitoring System, 3M, 
Maplewood, Minnesota) in persons with Hi-
SCI only. Skin Temperature (Tsk): will be 
monitored using TX-4 Skin Surface probes 
and Iso-Thermex Multichannel Thermometer 
(Columbus Instruments, Columbus, OH). 
Skin thermocouples will be taped to 12 sites 
on the anterior and dorsal trunk of the 
participant. Microvascular Perfusion (LDF): 
will be measured using laser probes on the 
skin of both ventral forearms and calves with 
a Periflux System 5000 Laser Doppler 
(Perimed, Stockholm, Sweden) for 
calculation of CVC. Sweat rate (SR): will be 
measured by the Quantitative Sweat 
Measurement System (WR Medical 
Electronics, Stillwater, MN) with capsules 
secured to 4 sites: left upper arm, left 
forearm, left mid-thigh, and left midcalf. 
Thermal Sensation (TS) and Thermal Comfort (TC): TS will be measured by a 9-point thermal sensation 
scale, while TC will be measured by a 6-point thermal comfort scale (attached).56 Tympanic 
temperature will be assessed in all participants using a Braun PRO 6000 infrared ear thermometer 
(Welch Allyn, Skaneateles Falls, NY). 
Hemodynamic Measurement Procedures: Brachial BP: BP will be measured at the brachial artery 
using the Carescape Dinamap V100 Automated BP Monitor (Carescape, Milwaukee, WI). BP will be 
obtained at 10-minute intervals throughout BL and Thermal Challenge and immediately pre and post 
LDF measurement for calculation of CVC. 
Sample Size and Statistical Approach: We are hypothesizing that after 2 hours of heat exposure, the 
average increase in Tcore of persons with Hi-SCI with the wet cooling vest will be 0.3±0.3°C compared 
to an increase of 0.6±0.3°C  (data from our prior study using an identical heat challenge, but with no 
vest).51  Therefore, a sample size of 10 participants would be needed to achieve a power of 81% for a 
two-sided, one-sample analysis at an alpha of 0.05. For Phase I (safety), descriptive statistics will be 
used to determine the number of participants who have a vest failure. Vest failure will be defined as any 
area of skin under the vest (Tsk) with a temperature <20°C and/or the number of participants who 
report a TS of “cold” or “very cold”. For efficacy testing, a 2 x 2 (condition, time) repeated measures 
ANOVA will be used to determine significant main or interaction effects. If main or interaction effects are 
determined, post hoc analysis will be performed using t-tests or appropriate non-parametric tests to 
determine significant differences between conditions. Significance will be set at an alpha level of 0.05.  
3a. Basic Information - Even if described under “Procedures”, list the following information, where pertinent: 
Table 1: Schedule of Assessments and 
Procedures 
Measures 
Acclimation 
BL 
Heat 
Run Time (min) 
30 
15 
120 
Cumulative Time (min) 
30 
45 
165 
*Tcore 
 
†† 
†† 
Skin Temperatures 
 
†† 
†† 
*Sweat Rate 
 
1x 
4x 
Thermal Sensation 
1x 
2x 
12x 
Thermal Comfort 
1x 
2x 
12x 
Laser Doppler Flow 
 
2x 
6x 
Brachial BP, O2 sat 
 
2x 
12x 
†† Tcore and skin temperature measurements will be 
monitored and collected simultaneously throughout the 
study. *Tcore and Sweat Rate in persons with Hi-SCI only. 

3a. i) Procedures to be used (e.g., biopsy, surgical operation, interview, experimental diet, infusion, drug 
administration, etc.) and with what frequency? 
Procedures 
Thermoregulatory Measurement Procedures: The following measurements will be obtained during 
BL and Thermal Challenge for all visits (Table 1).  
Tcore: will be monitored by an disposable forehead skin temperature sensor(Bair HuggerTM Spot OnTM 
Temperature Monitoring System, 3M, Maplewood, Minnesota)in persons with Hi-SCI only.  
 
In all participants:  
Skin Temperature (Tsk): will be monitored using TX-4 Skin Surface probes and Iso-Thermex 
Multichannel Thermometer (Columbus Instruments, Columbus, OH). Skin thermocouples will be taped 
to 12 sites on AB controls and 14 sites – 10 sites on the chest/abdomen (five on each side) and 4 sites 
on the bilateral hands and feet (2 on each side) on persons with Hi-SCI.  
Sweat rate measurement (QS): will be measured for 15 minutes, once during the baseline period and 4 
times during the thermal challenge at 30-minute intervals, for a total of 5 measurements. 
Microvascular Perfusion (LDF): will be measured using laser probes on the skin of both ventral 
forearms and calves with a Periflux System 5000 Laser Doppler (Perimed, Stockholm, Sweden) for 
calculation of CVC.  
Thermal Sensation (TS) and Thermal Comfort (TC): TS will be measured by a 9-point thermal sensation 
scale, while TC will be measured by a 6-point thermal comfort scale.56  
Tympanic temperature will be assessed using a Braun PRO 6000 infrared ear thermometer (Welch 
Allyn, Skaneateles Falls, NY). 
Hemodynamic Measurement Procedures:  
Brachial BP: BP will be measured at the left brachial artery using the Carescape Dinamap V100 
Automated BP Monitor (Carescape, Milwaukee, WI). BP will be obtained at 10-minute intervals 
throughout BL and Thermal Challenge. 
Blood Oxygen Saturation: Blood oxygen saturation will be recorded every 10 minutes. 
3a. ii) Description of procedures. If pharmacologic agents or radioisotopes are to be administered, provide 
dosages, mode of administration and duration of usage. 
Core temperature measurement (Tcore): will be monitored by an disposable forehead skin temperature 
sensor, (Bair HuggerTM Spot OnTM Temperature Monitoring System, 3M, Maplewood, Minnesota) in 
persons with Hi-SCI only. 
Skin temperature measurement (Tsk): will be monitored using TX-4 Skin Surface probes and Iso-
Thermex Multichannel Thermometer (Columbus Instruments, Columbus, OH). Skin thermocouples will 
be taped to 12 sites under the vest on the anterior and dorsal trunk of AB participants on AB controls 
and 14 sites – 10 on the anterior and dorsal trunk and 4 on both hands and feet- on persons with Hi-SCI. 
Microvascular Perfusion (LDF): will be measured using laser probes on the skin of both ventral forearms 
and calves with a Periflux System 5000 Laser Doppler (Perimed, Stockholm, Sweden) for calculation of 
CVC. 
Sweat rate (SR): will be measured by the Quantitative Sweat Measurement System (WR Medical 
Electronics, Stillwater, MN) with capsules secured to 4 sites: left upper arm, left forearm, left mid-thigh, 
and left midcalf (C5, T1, L3, and L5 dermatomes, respectively). 
Brachial BP & HR: will be measured at the brachial artery using the Carescape Dinamap V100 
Automated BP Monitor (Carescape, Milwaukee, WI) placed above the left elbow.  
Thermal Sensation (TS): TS will be measured by a 9-point thermal sensation scale (attached).  
Thermal Comfort (TC): TC will be measured by a 6-point thermal comfort scale (attached). 
Tympanic temperature will be assessed using a Braun PRO 6000 infrared ear thermometer (Welch 
Allyn, Skaneateles Falls, NY), along with other vital signs, e.g., BP, HR, O2 sat. 
 
3a. iii) Population to be studied, listing basis for selection or exclusion and number to be studied. 
Participants: Ten participants with high-level SCI (Hi-SCI: >T6) and 5 able-bodied (AB) participants 
matched for age (±5 years) and gender will be recruited for study participation. All subjects will be 
studied at the James J. Peters VA Medical Center, Bronx, NY. 
Participant Recruitment: Patients referred by their physician following routine physical examinations will 
be approached for potential study enrollment. Physicians will be informed of the inclusion and exclusion 

criteria and will be able to assure us that the patient is an appropriate study participant and that he/she 
is willing to speak with the study coordinators. 
1. Veterans with SCI responding to IRB-approved articles in lay publications and advertisements.  
2. Veterans with an ongoing relationship with our center (Metabolic, Pulmonary, or GI SCI clinics).  
Inclusion Criteria:  
1. 18-68 years of age 
2. SCI >1 year in duration.  
3. Level of SCI C4-T2, AIS A & B 
4. Gender and age-matched (±5 years) AB controls 
5. Euhydration (participants will be instructed to avoid caffeine and alcohol, maintain normal salt and 
water intake and avoid strenuous exercise for 24 hours prior to study). 
 
Exclusion Criteria:  
1. known cardiovascular, kidney or untreated thyroid disease;  
2. traumatic brain injury (mod-severe) 
3. diabetes mellitus;  
4. acute illness or infection;  
5. broken, inflamed, or otherwise fragile skin;  
6. pregnancy;  
7. BMI >30 kg/m2;  
8. smoking;  
 
 
3a. iv) If subjects are patients, will conventional therapy or diagnostic procedures be withheld or modified 
for the purpose of this study?  
No. Conventional therapy or diagnostic procedures will not be withheld or modified for the purpose of this 
study. 
3b. Multi-Site Studies  
Not applicable.  
 
3c. Possible Risks  
3c. i) List possible hazards to subjects and/or investigative personnel from the procedures, drugs, or 
isotopes to be employed. What monitoring or other safety precautions will be taken?  
Thermoregulatory Measurement Procedures 
Skin Temperature Monitoring (Tsk): Skin temperature measurement is non-invasive & not associated with 
risks. However, persons with sensitive skin could find the tape used to secure the thermocouple to be 
irritating.  
Core Temperature Monitoring (Tcore): The Bair HuggerTM Spot OnTM Temperature Monitoring System is 
non-invasive & not associated with risks. However, persons with sensitive skin could find the thermocouple 
adhesive to be irritating. Tcore measurement will be performed in subjects with Hi-SCI only (Visits 2 & 3).  
Tympanic temperature: is non-invasive and a disposable sleeve is used for each subject. The placement of 
the ear thermometer may feel uncomfortable. 
Sweat rate (SR) is non-invasive & not associated with risks. However, persons with sensitive skin may find 
the tape used to secure the capsules to the skin to be irritating.  
Thermal Sensation: is non-invasive & not associated with any risks.  
Thermal Comfort: is non-invasive & not associated with any risks. 
 
Hemodynamic Measurement Procedures  
Microvascular Perfusion: Microvascular Perfusion (LDF) measurement is a non-invasive measurement and 
is not associated with risks.  
Brachial Blood Pressure (BP) and Heart Rate (HR): Brachial BP and HR measurement is non-invasive & 
not associated with risks. The subject may feel the pressure of the inflated cuff to be uncomfortable. 
 
 
Thermal Challenge  
Hyperthermia: A potential risk to subjects is an increase in Tcore ≥ 38.0°C causing hyperthermia secondary 
to sitting in a warm thermal chamber at 35.0°C for up to 2 hours. This risk is greater in persons with higher 
levels of SCI compared to AB controls. The risk of hyperthermia will be minimized in all subjects by 

monitoring Tcore continuously throughout the study. Should the subjects’ Tcore reach 37.9°C, or if they 
complete 120 minutes in the warm thermal room, the protocol will be terminated, and subjects will be 
transferred to a cooler environment (22°C), covered with cool, wet blankets, and given cold liquids. 
Subjective symptoms of hyperthermia (headache, confusion, dizziness, nausea, feeling faint, etc.) and 
autonomic dysreflexia (AD) (increased BP, pounding headache, etc.) will also be assessed throughout the 
procedure, and if subjects are deemed at risk of hypothermia or AD, the protocol will also be terminated. To 
decrease the risk of AD, participants with SCI will be asked to empty their bladder prior to starting the 
protocol. 
There is a slight risk of heat-induced hypotension. This risk is greater in AB persons because their ability to 
peripherally vasodilate, in response to heat, remains intact as opposed to their SCI counterparts. This risk 
will be minimized by monitoring for symptoms of hypotension (systolic blood pressure (SBP) decrease >20 
mmHg from baseline levels, dizziness, lightheadedness, etc.) throughout the procedure and if subjects are 
deemed at risk of hypotension, the protocol will be terminated. 
Cooling Vest: There is a slight risk of the wet cooling vest irritating the skin. This risk will be minimized by 
instructing the subject to wear a standard T-shirt between the vest and their bare skin. Another potential 
risk to subjects is non-freezing cold injury due to wearing the cooling vest for a duration of 2 hours. The risk 
of non-freezing cold injury is greater in subjects with HI-SCI who have insentient skin. To minimize this risk, 
all subjects will wear a T-shirt under the vest and safety testing will first be conducted on AB subjects who 
will be able to determine if the sensation at any time is less (colder) than “cool”. If the vest is judged to be 
“cold” or any area of the vest is “cold”, the vest will be promptly removed, and technical adjustments will be 
made for safety. Only after safety is confirmed in AB subjects, will the vest be used in subjects with HI-SCI. 
The vest will self-regulate using feedback from multiple sensors to keep any material within its interior 
surface well above 17°C, which is the threshold necessary to cause a non-freezing cold injury with 
prolonged exposure. In an abundance of caution, the minimal vest temperature will be limited to ≥20°C. 
The risk of non-freezing cold injury will also be minimized by constant monitoring of skin temperature under 
the vest by use of skin thermocouples (12 sites in AB, 10 in Hi-SCI). If the temperature under the vest is 
determined to be <20°C, the vest will be promptly removed, and the protocol will be terminated. The risk of 
non-freezing cold injury to the skin is minimized as the vest will have been fully bench-tested to meet all 
safety requirements before human subject testing.  
Subject modesty: Subjects will wear minimal clothing (shorts and T-shirt) during the study to maximize bare 
skin exposure to the warm temperature. The exposure may exceed the subject’s modesty causing potential 
embarrassment. To minimize this risk, exposure will be limited to the area of the thermal chamber only and 
to the minimum number of research team members necessary. 
Additional unforeseen risks will be minimized by obtaining and reviewing a thorough medical history of 
prospective participants. Subjects and clinical experts will have the study objectives explained in detail and 
will be given the opportunity to ask questions about research procedures and the implications of the 
research. Moreover, study coordinators will be carefully selected that have experience in working with 
patients with SCI and have formed a good rapport with these individuals. In addition, we have structured 
the questionnaire to avoid questions about income and service connection, which have raised subject 
concerns in previous studies (where veterans refused to answer). 
 
3d. Possible Benefits  
There may be no direct benefit to the subject for participating in this study. However, if an abnormality is 
identified during the study, it will be brought to the attention of the subject and the subject’s physician. The 
information which is obtained may be useful scientifically and clinically helpful to others. If the self-
regulating cooling vest proves to be an effective treatment for maintenance of Tcore during warm 
temperature exposure in this study, it or a similar device may be considered as an intervention to address 
thermodysregulation following a spinal cord injury. 
 
 
4. PREVIOUS WORK DONE BY YOU OR YOUR COLLABORATORS ON THIS OR RELATED 
PROJECTS, LISTING PUBLICATIONS  
 
Preliminary Studies 
We have shown that 8 persons with tetraplegia (NLI C5-C7, ASIA Impairment Scale [AIS] A-B) exposed to 
warm temperatures (35°C) for ~2 hours had a significantly greater rise in Tcore than 9 matched controls 

(0.8±0.3°C vs -0.06±0.2°C; p<0.001, respectively).50 Interruption of sympathetic pathways for control of 
heat dissipating mechanisms was supported by significantly lower plasma NE levels (p<0.001) in the 
tetraplegic group compared to controls during BL and after Heat Challenge conditions. Subjective thermal 
sensation was rated as “hot” to “very hot” after 2 hours of challenge but was not significantly different than 
that of controls.50 
In 20 persons with Hi-SCI (NLI C4-T4, AIS A-B) who were exposed to the identical warm challenge, we 
found a greater rise in average Tcore than 19 matched AB controls (0.6±0.3°C vs. -0.1±0.2°C, p<0.001, 
respectively). Thirteen of the 20 (65%) had evidence of greater sympathetic interruption (lower blood 
pressure and sweat rate than controls) and demonstrated a greater rise in Tcore than 7 persons (35%) with 
Hi-SCI (0.8±0.3°C vs. 0.3±0.3°C; p<0.001, respectively) whose blood pressure and sweat rate were not 
different than controls, despite NLI and AIS grades not being significantly different between the two Hi-SCI  
groups.51 The lower blood pressure and decreased sweat rate in 13/20 participants with Hi-SCI signify 
greater vasomotor disruption, greater sympathetic cholinergic interruption, and the least amount of 
evaporative heat loss. In support of the significance of these findings in achieving optimal health and QOL, 
our lab conducted a study assessing subjective comfort during the warmer seasons, which surveyed 100 
participants with SCI (50 persons with tetraplegia (C3-C8, AIS A-D), 50 with paraplegia (T1-T12, AIS A-D), 
and 50 age-matched AB controls (unpublished data).  Both tetraplegia and paraplegia groups reported an 
impaired ability to stay comfortable when compared to the AB group. The negative effect on social activities 
was greatest in the tetraplegia group. In addition, once feeling overheated, a greater proportion of the 
participants in the tetraplegic group reported needing significantly more time (≥20 minutes) to return to 
feeling comfortable than those in either the paraplegic or AB groups. 
Our “smart” cooling vest is designed to 
provide a large area of contact with the 
user with a material that is a good 
thermal conductor and will be 
maintained at a uniform temperature 
10-15°C cooler than the user’s skin 
temperature beneath the vest. It can 
automatically regulate temperature by 
closed-loop control through processing 
skin temperature and Tcore for safety 
and efficacy. The vest is novel as it is 
electrically powered, utilizing a 
lightweight transformer to 
thermoelectrically cool water (i.e., 
Peltier thermal effect), and a low-power turbine to pump the cooled water through a web of thin-walled 
plastic tubes embedded in the vest (Figure 1: (A) Arduino (microprocessor), (B) two Peltier transformers 
with heat sinks and cooling fans, and (C) centrifugal water pump (turbine).  
The thermoregulation program of the VA RR&D 
Center for the Medical Consequences of Spinal Cord 
Injury and Dr. Hao Su, Picasso Intelligence L.L.C. 
have developed an initial prototype of a feedback-
controlled cooling vest specifically designed for 
persons with SCI with an impaired ability to dissipate 
heat (Figure 2). 
Figure 2. (A). Prototype of the vest and control board 
and (B). Tubes and water junctions 
Figure 1. Overview of the smart cooling vest, including AI powered 
controller, electrical circuits (black lines) and fluid pathways (blue lines). 

The turbine has a much smaller power requirement (9.6 watts) than each Peltier transformer (60 watts) 
and, thus, can be run at maximum speed whenever cooling is powered on to maintain the circulation of 
cooled water. The cold side of each transformer is attached to a water block to cool the returning warmed 
water entering the block. The heat side of each transformer has an aluminum heat sink and a cooling fan 
capable of removing large amounts of heat from the module (Figure 3). Cooled water from the 
transformers is pumped by the turbine into six individual tubes. The tubes circulate cooled water through 
the vest before entering a second junction that merges them into one tube for return of the warmed water to 
the water block for re-cooling. PVC tubes (6.25 mm in diameter) were chosen for their higher thermal 
conductivity as compared to other plastic tubing. The tubes were sewn into the inside surface of the vest. 
The vest material is a lightweight, absorbent polymer that, if saturated 
with water, will use evaporation to provide additional heat loss over 
several hours (3-4 hrs). Most cooling vests are passive and use either 
conduction or evaporation to dissipate body heat. Our vest is 
designed to have the potential to selectively use either or both to 
restore some of the interrupted thermoregulatory function of 
conduction (vasodilation) and evaporation (sweating) in Veterans with 
Hi-SCI to optimize heat dissipation during ambient heat exposure. The 
inner lining of the vest is a thin, water-resistant material designed to 
minimize the user’s clothing from getting wet. The large surface area 
of the cooling vest is designed to provide a sufficient interface for heat 
exchange to increase the rate of heat conduction from core to skin by 
lowering the expected skin temperature (~35ºC) during heat 
challenge. Lowering skin temperature by 10-15ºC serves to increase 
the temperature gradient between core and skin to increase the rate 
of heat dissipation from the body. The cool vest also functions as an insulator, preventing ambient heat 
from conducting heat into the user’s torso.  
Temperature Regulation with Feedback Control: Suzurikawa et al. studied a “body heat removal 
system” utilizing thermo-electric cooling intended for persons with SCI and tested it in 5 AB participants.48 
However, their device did not use closed-loop temperature control, only cooled the back, and they did not 
report further testing in persons with SCI. Power for our “smart” vest is modulated by a closed-loop 
feedback control loop to increase safety and efficacy. The microprocessor receives Tcore information from 
thermistor sensors taped to both axillae and skin temperature information from thermistor sensors taped to 
areas of the trunk with the greatest contact with the cool vest. Axillary measurements of Tcore are reliable 
and typically 1ºC less than rectal measurement.59,60 Therefore, Tcore values of ≥36.6ºC and ≤35.4ºC will be 
used as thresholds to power on or off the vest, respectively. Threshold Tcore temperature values can also 
be manually entered, e.g., ±0.5 ºC from the user’s measured baseline Tcore. Skin temperature values of 
>33ºC and <20ºC will be used to power on and power off the vest, respectively. Sensors monitoring 
circulating water temperature will also feed information to the microprocessor. All thermistors assess 
temperature every 5 seconds and information sent to the microprocessor is filtered to provide a moving 
average of the last ten measurements. The skin temperature threshold of <20ºC to power off the vest will 
override Tcore temperature to protect the skin from non-freezing cold injury, a safety feature designed to 
prevent non-freezing cold injury (skin temperatures < ~17°C for prolonged periods)61 in persons with Hi-SCI 
who have insentient skin below their level of injury.1-3   
The current prototype of the vest possesses the key features of the hardware and software requirements to 
sense and control human body temperatures (Figure 2). We will optimize the current prototype to develop 
a new version of the vest (Prototype II) by incorporating more powerful Peltier transformers (40 Watt of the 
current prototype to 60 Watt for Prototype II) for a larger range of temperature control (0-5°C of current 
prototype to 10-15°C), a larger web of thin-walled plastic tubes to increase contact area for heat 
conduction, improved feedback control of body temperature to minimize response delay (e.g., thermal 
regulation of body temperature usually takes several minutes to respond to external control), and validation 
of safety mechanisms. Dr. Su will direct an engineer at Picasso Intelligence to leverage Artificial 
Intelligence (AI)-powered optimal control algorithms to rapidly determine control parameters to maintain the 
desired Tcore. The AI-based neural network controller will improve both transient response and steady-
state response of the temperature control system which typically involves time delay in temperature 
response.62 The neural network-based controller will perform adaptive control through learning processes to 
 
Figure 3. Thermoelectric Peltier 
cooler with water block, cooling fans, 
and cooling fins.  

overcome the time delay of temperature response. The control algorithm (implemented on a 
microprocessor with real-time control (A in Fig. 1) will have a three-layer neural network,62 including a 
hidden layer, thus combining the advantages of the standard proportional–integral–derivative (PID) control 
and a self-learning neural network. The input of the neural network includes reference temperature and 
body temperature sensor information. The three outputs of the hidden layer will be set as proportional P, 
integral I, and derivative units D, respectively. During system operation, the neural network is online-trained 
to automatically adjust the control parameters (P, I, D). The neural network will be able to learn the 
controller parameters (PID), resulting in more individualized thermal regulation for different users. Dr. Su is 
experienced in human-in-the-loop control of human bio-systems, demonstrated by optimizing human 
performance with reinforcement learning-based optimal control algorithms.63 Picasso Intelligence will follow 
FDA guidelines for bench testing of medical devices to assess the performance of Prototype II. Key criteria 
include 1) accuracy of Tcore and skin temperature measurement (within 1°C), 2) responsiveness of closed-
loop control (within 1°C), mass within 5 kg (target weight, 2.9 kg).  
 
5. SIGNIFICANCE OF THIS RESEARCH.  
Incidence & Prevalence of SCI: In the US alone, the estimated occurrence of new SCI is 18,000 cases 
each year with approximately 299,000 people currently living with SCI. Average lifetime costs for medical 
care and living expenses for a person with incomplete tetraplegia, the most common neurological form of 
SCI, is approximately 4 million dollars.64 In addition, SCI is one of the most labor-intensive and expensive 
chronic conditions to the Veterans Health Care Administration (VHA).65 
Significance of Current Research: Current clinical recommendations for persons with SCI during hot 
weather are quite general: avoid direct sunlight, dress sparingly, drink plenty of fluids, and stay indoors 
during midday on hot, humid days. There are also no standardized interventions that have been proven to 
stabilize Tcore during heat exposure after SCI. The goals of this proof-of-concept pilot study are: 1) to 
refine the current prototype to meet bench standards prior to human testing; 2) determine the safety and 
tolerability of a feedback-controlled “smart” cooling vest using able-bodied (AB) controls; and 3) to 
determine the efficacy of the wet “smart” cooling vest to maintain Tcore (within 0.3°C) and improve thermal 
comfort in participants with Hi-SCI during 2 hours of controlled warm environment (35°C). If efficacious, we 
intend to submit a full Merit Review application to collaborate with the Human Engineering Research 
Laboratory (HERL: letter of support provided by Dr. Rory Cooper, Director of HERL) to make the vest more 
appropriate for home testing to determine effectiveness in improving societal participation and QOL in 
Veterans with SCI during warmer seasons, residing in or traveling to hot climate zones. We will request the 
assistance of the VA’s Technology Transfer Program to successfully commercialize a safe and practical 
cooling vest for vulnerable individuals. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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