Feasibility Study for VCool™ Intranasal Cooling System in Healthy Volunteers
Phase: NA
Conditions: Targeted Temperature Management
Sponsor: NeuroIntact Inc.

Clinical Study Protocol  
Feasibility Study for VCool™ Intranasal Cooling System in Healthy Volunteers 
 
Sponsor: 
NeuroIntact, Inc. 
1100 Wicomico Street, Suite 330 
Baltimore, MD 21230 
Protocol Number: 
00080424 
Version: 
2.0 
Date: 
25 November 2025 
Device Name: 
VCool™ Intranasal Cooling System 
Development Phase: 
Pilot Study 
 
 
This clinical study will be conducted according to the protocol and in compliance with ISO 
14155:2020, Clinical investigation of medical devices for human subjects, good clinical practice 
(GCP); 21 CFR 812 Investigational Device Exemptions, ICH Harmonized Guideline GCP 
E6(R3) and with other applicable regulatory requirements. 
 
 
CONFIDENTIALITY STATEMENT 
This document contains the confidential information of NeuroIntact, Inc.  Do not copy or 
distribute without written permission from the Sponsor. 
 

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Table of Contents 
TABLE OF ABBREVIATIONS ...................................................................................................4 
KEY ROLES AND RESPONSIBILITIES ..................................................................................5 
PROTOCOL APPROVAL PAGE ...............................................................................................6 
INVESTIGATOR PROTOCOL AGREEMENT .......................................................................7 
1 
PROTOCOL SYNOPSIS .......................................................................................................8 
2 
INTRODUCTION ................................................................................................................10 
2.1 
Background ......................................................................................................................10 
2.2 
Study Objective ................................................................................................................10 
2.3 
Risk and Benefit Assessment ..........................................................................................10 
2.3.1 
Potential Risks ............................................................................................................10 
2.3.2 
Risk Mitigation ...........................................................................................................11 
2.3.3 
Potential Benefits .......................................................................................................11 
2.4 
Study Rationale ................................................................................................................11 
3 
STUDY DEVICE ..................................................................................................................12 
3.1 
Device Description ...........................................................................................................12 
3.2 
Indications for Use ...........................................................................................................12 
4 
INVESTIGATIONAL PLAN ..............................................................................................12 
4.1 
Study Design .....................................................................................................................12 
4.2 
Study Site ..........................................................................................................................13 
4.3 
Participant Enrollment ....................................................................................................13 
5 
STUDY ENDPOINTS ..........................................................................................................13 
5.1 
Primary Endpoints...........................................................................................................13 
5.2 
Secondary Endpoint.........................................................................................................13 
5.3 
Safety Considerations ......................................................................................................13 
6 
STUDY POPULATION .......................................................................................................13 
6.1 
Inclusion Criteria .............................................................................................................13 
6.2 
Exclusion Criteria ............................................................................................................14 
6.3 
Study Duration .................................................................................................................14 
7 
STUDY PROCEDURES ......................................................................................................15 
7.1 
Pre-screening ....................................................................................................................15 
7.2 
Screening ...........................................................................................................................15 
7.2.1 
Informed Consent ......................................................................................................15 
7.3 
Study Enrollment .............................................................................................................15 
7.3.1 
Participant Identification ..........................................................................................15 
7.3.2 
Participant Stipend ....................................................................................................15 
7.4 
Eligibility ...........................................................................................................................16 
7.5 
Baseline Data ....................................................................................................................16 
7.6 
Procedure ..........................................................................................................................16 
7.6.1 
VCool System Set Up .................................................................................................16 
7.6.2 
MR Imaging procedure .............................................................................................17 
7.6.3 
Participant Set Up and Monitoring ..........................................................................17 
7.6.4 
VCool System Shut Down .........................................................................................19 
8 
EARLY PARTICIPANT WITHDRAWAL OR DISCONTINUATION ........................19 
9 
EARLY STUDY END ..........................................................................................................20 
10 ADVERSE EVENTS.............................................................................................................20 

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10.1 
Definition of an Adverse Event .......................................................................................20 
10.2 
Definition of a Serious Adverse Event ...........................................................................21 
10.3 
Severity of Adverse Events and Serious Adverse Events .............................................22 
10.4 
Outcome of Adverse Events and Serious Adverse Events ...........................................22 
10.5 
Assessment of Relatedness to Study Product .................................................................23 
10.6 
Reporting Serious Adverse Events .................................................................................23 
10.6.1 
Serious Adverse Event Information to Report ........................................................24 
11 POTENTIAL ANTICIPATED ADVERSE EVENTS .......................................................24 
11.1 
Immediate Post-Procedure Observations .......................................................................24 
11.2 
Unanticipated Adverse Device Effect .............................................................................24 
11.3 
Reporting ..........................................................................................................................24 
12 DATA ANALYSIS ................................................................................................................25 
12.1 
Primary Analysis ..............................................................................................................25 
12.2 
Secondary Analysis ..........................................................................................................25 
12.3 
Populations for Analysis ..................................................................................................25 
12.4 
Imaging Data analysis......................................................................................................25 
13 RESPONSIBILITIES ...........................................................................................................25 
13.1 
Data Quality Assurance ...................................................................................................25 
13.2 
Protocol Deviations ..........................................................................................................26 
14 PARTICIPANTS LOST TO FOLLOW-UP ......................................................................26 
15 INSTITUTIONAL REVIEW BOARD................................................................................26 
16 INVESTIGATOR REPORTS ..............................................................................................27 
17 TRAINING ............................................................................................................................27 
18 STUDY DEVICE ACCOUNTABILITY ............................................................................28 
19 ETHICS/PROTECTION OF HUMAN PARTICIPANTS ................................................28 
19.1 
Ethical Conduct of the Study ..........................................................................................28 
19.2 
Participant Confidentiality .............................................................................................28 
20 ADMINISTRATIVE CONSIDERATIONS .......................................................................28 
20.1 
Protocol Approval and Amendment(s) ...........................................................................28 
20.2 
Case Report Form Completion .......................................................................................28 
20.3 
Archiving Study Documents ............................................................................................29 
21 REFERENCES .....................................................................................................................29 
 
 
 

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TABLE OF ABBREVIATIONS 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BSAS 
Bedside Shivering Assessment Scale 
℃ 
Degrees Celsius 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CT 
Computed Tomography 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ID 
Identification 
IDE 
Investigational Device Exemption 
IFU 
Instructions For Use 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
MAE 
Major Adverse Event 
PI 
Principal Investigator 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
TEAE 
Treatment Emergent Adverse Event 
TTM 
Targeted Temperature Management 
UADE 
Unanticipated Adverse Device Effect 
 
 
 

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KEY ROLES AND RESPONSIBILITIES  
 
 
 
 
Contact Information 
Sponsor: 
NeuroIntact, Inc. 
Address: 
1100 Wicomico Street, Suite 330 
Baltimore, MD 21230 
Contact: 
Bryan Wand 
Telephone:  
443.822.9482 
Email:  
bwand@neurointact.com 
Principal Investigator: 
 Neeraj Badjatia, MD 
Address: 
Gudelsky Building 
University of Maryland Medical Center 
Baltimore, MD 21201 
Telephone:  
410.328.4515 
Email:  
nbadjatia@som.umaryland.edu 
 
 
 

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PROTOCOL APPROVAL PAGE 
 
Protocol Title 
Feasibility Study for VCool Intranasal Cooling System in Healthy 
Volunteers 
 
Protocol Number 
00080424 
 
Protocol Version 
2.0 
 
Date of Issue 
01 August 2024 
 
Sponsor Name 
NeuroIntact, Inc.  
 
Address 
1100 Wicomico Street, Suite 330 
Baltimore, MD 21230 
 
This clinical study protocol was subjected to critical review. The information it contains is 
consistent with current knowledge of the risks and benefits of the investigational product, as 
well as with the moral, ethical, and scientific principles governing clinical research and will 
be conducted according to the protocol and in compliance with ISO 14155:2020, Clinical 
investigation of medical devices for human subjects, good clinical practice; 21 CFR 812 
Investigational Device Exemptions, ICH Harmonized Guideline Good Clinical Practice (GCP) 
E6(R3) and with other applicable regulatory requirements. 
 
Sponsor: 
Name: Bryan Nicholson 
Title: President & CEO 
Signature: ________________ 
Date: ____________________ 
 
 

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INVESTIGATOR PROTOCOL AGREEMENT 
 
Protocol Title 
Feasibility Study for VCool Intranasal Cooling System in Healthy 
Volunteers 
Protocol Number, Version 00080424, Version 2.0 
By my signature, I 
1. Agree to conduct the study in accordance with the relevant, current protocol and will only deviate 
from the protocol when necessary to protect the safety, rights, or welfare of the participant. 
2. Agree to personally conduct or supervise the described investigation. While the PI may delegate one 
or more functions to an associate or sub-investigator, the PI retains overall responsibility for proper 
conduct of the study. 
3. Agree to inform any patients that the study product is being used for investigational purposes and I 
will ensure that the requirements relating to obtaining informed consent in 21 CFR Part 50 and 
Institutional Review Board (IRB) review and approval in 21 CFR Part 56 are met. 
4. Agree to report to the Sponsor adverse experiences that occur during the investigation in accordance 
with 21 CFR 812.150. I have read and understand potential risks and side effects of the study 
product. 
5. Agree to ensure all associates, colleagues, and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments. 
6. Agree to maintain adequate and accurate records. 
7. Ensure that an IRB that complies with the requirements of 21 CFR Part 56 will be responsible for the 
initial and continuing review and approval of the clinical investigation. I agree to promptly report to 
the IRB all changes in the research activity and all unanticipated problems involving risks to human 
participants and others. I will not make any changes in the research protocol without consent from 
the Sponsor and will not institute those changes in the research protocol until after approved by the 
Sponsor and IRB, except where necessary to eliminate apparent immediate hazards to human 
participants. 
8. Agree to comply with all other requirements regarding the obligations of clinical 
investigators and all other pertinent requirements in 21 CFR Part 812. 
9. Agree to participate in an appropriate training program as part of the study initiation. 
10. Agree to allow staff of the Sponsor and its authorized representatives, as well as representatives from 
regulatory agencies, to review, inspect and copy any documents pertaining to this clinical investigation.  
This document contains confidential information belonging to the Sponsor, and therefore may not be 
disclosed to any other person or entity without the prior written permission of the Sponsor unless such 
disclosure is required by law or regulation or required for the execution of the PI’s responsibilities 
pertaining to this study. 
Investigator Signature  
I have read and understand the contents of the clinical protocol including this Statement of Investigator 
Compliance.  I agree to follow and abide by the guidelines set forth in this document.  
 
 
 
 
 
 
 
Principal Investigator Name (print) 
 
 
 
 
 
 
 
 
 
 
 
 
  

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Principal Investigator Signature  
 
 
 
 
             Date 
 
1 PROTOCOL SYNOPSIS 
Protocol Title: 
Feasibility Study for VCool Intranasal Cooling System in Healthy 
Volunteers 
Protocol Number: 
00080424 
Version: 
2.0 
Date: 
01 August 2024 
Development Phase: Pilot Study 
Sponsor: 
NeuroIntact, Inc.  
1100 Wicomico Street, Suite 330 
Baltimore, MD 21230 
Study Objective: 
The objective of this study is to evaluate the performance and safety of 
the VCool Intranasal Cooling System in healthy adult volunteers.  The 
study is designed to gather preliminary data regarding air flow rates and 
time required to reduce core body temperature to 35.5℃ and maintain the 
temperature between 35℃ and 36℃ for one hour after cooling.  
Number of Sites / 
Number of 
Participants: 
The study will be conducted at one site in Maryland.   
A total of 10 participants need to complete the study.  
Primary Endpoints: 1. To confirm the VCool System can lower core body temperature 
to 35.5℃ within 2 hours. 
2. To confirm the VCool System can maintain a core body 
temperature between 35℃ and 36℃ for one hour after cooling.  
3. To demonstrate the differential impact of VCOOL system 
between core body and brain temperature 
Secondary 
Endpoint: 
1. To assess the shivering experienced by participants based on the 
4-point Bedside Shivering Assessment Scale (BSAS). 
Safety Evaluation: 
All treatment emergent adverse events (TEAEs) reported by participants 
will be tabulated. 
Each adverse event (AE) will be evaluated by the Investigator in terms of 
seriousness, severity (mild, moderate, severe) and relationship (not 
related, possibly related, probably related, definitely related) to the study 
device. 
Study Design: 
This is a single-center, prospective, open label, feasibility study in 
healthy adult participants.  Participants will be monitored for up to 2 
hours while using the VCool System to determine if the target 
temperature of 35.5℃ is reached. If the target core body temperature is 
reached within 2 hours, the participant will be monitored for an additional 
hour to determine if the VCool System can maintain the participant’s core 
body temperature between 35℃ and 36℃ for one hour. 

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During the study, the participants will have their blood pressure and 
temperature monitored and will be assessed for shivering and adverse 
events. 
Study Duration: 
The overall study participation for each participant will be one visit 
lasting approximately 4 hours. Study enrollment is anticipated to be 
completed within two weeks.  
Study Device: 
VCool Intranasal Cooling System 
Proposed Indication 
for Use: 
The VCool Intranasal Cooling System is intended for temperature 
reduction in adult patients where cooling is indicated. 
Eligibility Criteria: 
Participants who meet all the inclusion criteria and none of the exclusion 
criteria are eligible for enrollment in the study. 
Inclusion Criteria 
1. Male or female ages 18 to 55. 
2. An Institutional Review Board (IRB) approved informed consent is 
signed and dated prior to any study-related activities. 
3. Baseline core body temperature between 36.8℃ and 37.5℃. 
4. Have the ability to understand the requirements of the study and 
are willing to comply with all study procedures.  
5. In the opinion of the Investigator, are able to participate in the 
study. 
Exclusion Criteria 
1. History of cardiovascular, respiratory, or metabolic disorder 
2. Any contraindication to undergoing Magnetic Resonance Imaging 
(MRI) 
3. Pregnant 
4. Severe peripheral vascular disease 
5. History of Raynaud’s disease 
6. Currently experiencing a respiratory infection 
7. Chronic rhinosinusitis 
8. History of sickle cell disease 
9. History of cold agglutinin disease 
10. History of cryoglobulinemia  
11. Known deviated septum or nasal deformity 
12. History of nosebleeds or a nosebleed within past 24 hours 

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13. Use of antipyretics or other medications affecting body temperature 
within the past 24 hours. 
2 INTRODUCTION 
2.1 
Background 
Inducing normothermia or mild hypothermia is known to have therapeutic benefits in various 
medical conditions where neuronal damage can occur, including stroke and cardiac arrest 
patients [1-9]. Among numerous benefits, cooling, known as Targeted Temperature Management 
(TTM), has been shown to reduce cerebral edema and neurogenic fever. Numerous studies have 
been completed inducing normothermia or mild hypothermia in healthy volunteers using 
different cooling technologies including surface and intravascular approaches with no serious 
adverse events [10-14].This study is the first to use thermoelectrically cooled air delivered 
through the nasal passages via nasal cannula to reduce core body temperature. 
The VCool Intranasal Cooling System has been previously studied in a porcine animal model 
which demonstrated safety and efficacy [15]. In this study, swine were cooled and met the 
primary outcome of effective cooling (34°C from 38.1°C) There was no secondary short or 
medium evidence of injury in CT imaging of the animal’s snout anatomy, CT perfusion of the 
brain, or histological analysis of the brain and snout. 
2.2 
Study Objective 
The objective of this study is to evaluate the performance and safety of the VCool Intranasal 
Cooling System (VCool) in healthy adult volunteers.  The study is designed to gather 
preliminary data regarding air flow rates and time required to reduce core body temperature to 
35.5℃ and maintain the temperature between 35℃ and 36℃ for one hour after cooling.  
Additional data will be obtained on whether intranasal cooling results has a differential 
temperature impact on core body temperature as compared to brain temperature.  
The data collected will help to develop automated cooling models and the control system 
algorithm by examining participant cooling response as a function of air flow rate and time the 
air is supplied to the participants.  
2.3 
Risk and Benefit Assessment 
2.3.1 
Potential Risks 
The only known study-related risk is the use of a nasal cannula to deliver cold air to the 
participant. The potential risks associated with this delivery are:  
Nosebleed 
Shivering 
Irritation of the nasal passages 

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Skin irritation at the site of the cannula 
Nasal congestion 
Over cooling 
Participants will be de-identified using a study specific number at the time of enrollment.  All 
Case Report Forms (CRFs) will be labeled with the de-identified participant identification (ID) 
number. No identifiable participant identification information will be provided to NeuroIntact.  
Information collected for this study is confidential.  However, officials of the Food and Drug 
Administration (FDA) or other regulatory agencies may research records during the ordinary 
course of carrying out their functions.  A Sponsor representative may also inspect the research 
records to make certain the study data is accurate.  The Investigator, regulatory agencies, and the 
Sponsor will protect the confidentiality of the records. 
2.3.2 
Risk Mitigation 
The protocol has been designed to minimize the risks to study participants enrolled in the study.  
In general: 
• Prior to study enrollment the Investigator must ensure the participant meets the 
inclusion/exclusion criteria 
• Each participant will be fully informed about the conditions of study participation, and the 
risks and potential benefits of the study procedure and asked to provide an executed Informed 
Consent prior to being enrolled in the study 
• Institutional Review Board (IRB) review and approval of the study protocol, Informed 
Consent Form, and any other participant-facing documents will be obtained prior to study 
initiation. 
• The participant’s core temperature will be continuously monitored with direction to adjust 
the VCool if the core temperature is <35°C for a sustained period of 5 minutes, to mitigate 
overcooling of the participant 
• If the participant develops a nosebleed, the VCool will be stopped 
• Participants will be assessed for shivering and if severe according to the Bedside Shivering 
Assessment Scale, the VCool flow and temperature will be adjusted 
2.3.3 
Potential Benefits 
The information obtained in this study will not benefit the study participants directly but may aid 
future patients requiring cooling of body temperature. 
2.4 
Study Rationale 
The two leading categories of TTM devices include surface cooling systems and intravascular 
cooling systems, both of which have disadvantages. Surface systems limit patient access, are 
difficult to transport, and can cause skin irritation and shivering. Intravascular systems require an 
invasive procedure and can lead to infection. Both approaches are also intolerable to awake 
patients. The VCool Intranasal Cooling System is anticipated to overcome these issues as well as 
cool patients rapidly and be easy to use. 

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3 STUDY DEVICE 
3.1 
Device Description 
The VCool Intranasal Cooling System is intended to cool the core body temperature of patients 
for whom cooling is medically indicated. The VCool System produces a flow of 
thermoelectrically cooled air from an external source (hospital compressed wall medical air or 
oxygen). The air flow is delivered from the VCool System to the patient via an insulated air 
delivery tube. The air delivery tube is insulated to keep the air cooled. A two-prong nasal 
cannula is attached to the delivery tube and placed in the patient’s nostrils. Cooled air enters the 
nasal passages and exits freely through the nose and mouth. The nasal prongs do not create a seal 
at the nostrils and therefore do not create excess airway pressure. The VCool System does not 
utilize invasive catheters, surface cooling pads, or any cooling agents. The VCool System is not 
used to deliver respiratory support.   
The VCool is a small device weighing less than 25 pounds. There is an internal power source, a 
Peltier (thermoelectric cooling unit), air tubing, and thermistors. The system can deliver air flow 
rates of up to 40 liters per minute set to a temperature of 5°C at the end of the cannula. All parts 
of the system are constructed of biocompatible materials and designed for electrical safety. In 
this study, the VCool will be connected to a medical grade air compressor which will supply the 
air for cooling. A commercially available nasal cannula will be used to deliver the cooled air. 
3.2 
Indications for Use 
The VCool Intranasal Cooling System is intended for temperature reduction in adult patients 
where cooling is medically indicated. 
4 INVESTIGATIONAL PLAN 
4.1 
Study Design 
This is a single-center, prospective, open label, feasibility study in healthy adult participants.  
Eligible participants who have signed an informed consent will be enrolled in the study.  The 
participant will be assigned a unique ID number. After obtaining relevant demographic 
information, testing will ensue. 
Baseline vital sign measurement (heart rate, temperature, blood pressure, respiratory rate) will be 
obtained.  The participant will then undergo continuous MRI of the brain to include sequences 
that enable thermography.  Baseline imaging sequences will take approximately 30 minutes.  The 
the Investigator or designee will turn on the VCool System, while the VCool remains outside of 
the MRI suite, for up to two hours or until the target temperature of 35.5℃ is reached. Body 
temperature will be continuously measured using a MRI compatible thermometer.  During the 
cooling period and once endpoint is reached the the participant will undergo repeated MRI with 
thermography. Once study endpoint is reached, the participant will be taken off of VCool and 
MRI thermography.  If the target core body temperature is reached before 2 hours, the participant 
will be monitored until two hours are completed to determine if the VCool System can maintain 
the participant’s core body temperature between 35℃ and 36℃ for one hour. 

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During the study, the participants will have their temperature monitored and will be assessed for 
shivering and adverse events. 
Study participation is one visit lasting approximately 4 hours. 
4.2 
Study Site 
The study will be conducted at the University of Maryland School of Medicine HSF III research 
facility. 
4.3 
Participant Enrollment 
Participants will be screened for inclusion in the study to ensure that 10 participants complete the 
study. 
5 STUDY ENDPOINTS 
5.1 
Primary Endpoints 
1. To confirm the VCool System can lower core body temperature to 35.5℃ within 2 hours. 
2. To identify whether cooling with the VCool System results in a gradient between brain and 
core body temperature. 
3.  To confirm the VCool System can maintain a core body temperature between 35℃ and 
36℃ for one hour after cooling. 
5.2 
Secondary Endpoint 
4. To assess the shivering experienced by participants based on the 4-point Bedside Shivering 
Assessment Scale (BSAS). 
5.3 
Safety Considerations 
All treatment emergent adverse events (TEAEs) reported by participants will be tabulated. 
Each adverse event (AE) will be evaluated by the Investigator in terms of seriousness, severity 
(mild, moderate, severe) and relationship (not related, possibly related, probably related, 
definitely related) to the study device. 
6 STUDY POPULATION 
6.1 
Inclusion Criteria 
Participants are eligible for enrollment if all the inclusion criteria are met: 
1. Male or female ages 18 to 55 

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2. An Institutional Review Board (IRB) approved informed consent is signed and dated prior to 
any study-related activities 
3. Core body temperature between 36.8℃ and 37.5℃ 
4. Have the ability to understand the requirements of the study and are willing to comply with 
all study procedures 
5. In the opinion of the Investigator, are able to participate in the study 
6.2 
Exclusion Criteria 
Participants are not eligible for enrollment if any of the exclusion criteria apply: 
1. History of cardiovascular, respiratory, or metabolic disorder. 
2. Any contraindication to undergoing Magnetic Resonance Imaging (MRI) 
3. Pregnant 
4. Severe peripheral vascular disease 
5. History of Raynaud’s disease 
6. Currently experiencing a respiratory infection 
7. Chronic rhinosinusitis 
8. History of sickle cell disease 
9. History of cold agglutinin disease 
10. History of cryoglobulinemia  
11. Known deviated septum or nasal deformity 
12. History of nosebleeds or a nosebleed within past 24 hours 
13. Use of antipyretics or other medications affecting body temperature within the past 24 hours 
6.3 
Study Duration 
Each participant’s involvement in the study will be one study visit lasting approximately 4 hours.  
No follow-up or subsequent participant involvement is required.  Study enrollment is expected to 
be completed within 8 weeks. 

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7 STUDY PROCEDURES 
7.1 
Pre-screening 
Potential participants will be pre-screened by a designated member of the study team to 
determine if the potential participant meets any of the exclusionary criteria based on medical 
history.  If the participant is determined to be potentially eligible for participation, they will be 
scheduled for a screening visit at the study site.  
7.2 
Screening 
7.2.1 
Informed Consent 
Study staff trained in basic human research subjects protection will explain the study protocol, 
procedures, and objectives to the volunteer and obtain written informed consent for participation 
in the study prior to performing any study procedures, in accordance with the requirements 
outlined in the Code of Federal Regulations (CFR) Title 45, Part 46 and Title 21, Part 50. This 
will be done by reviewing all the information contained in the informed consent form (ICF), 
allowing the volunteer ample time to review the form, ask questions, and have their questions 
answered to the satisfaction of the volunteer.  The ICF will be presented to the volunteer in a 
language that is fully comprehensible to them. 
Volunteers wishing to participate will be asked to sign and date the ICF and will be provided 
with a copy for their records.  The original will be maintained with the participant’s study 
records. 
7.3 
Study Enrollment 
7.3.1 
Participant Identification 
If the volunteer is willing to participate in the study and has signed and dated the ICF, they will 
be assigned a unique ID number.  The ID number is a 2-digit number assigned sequentially (i.e., 
01, 02, 03). The ID number will be written on each page of the CRF, and all other documents 
related to the participant. 
The site will maintain a screening and enrollment log for participant identification, to which all 
consented participants will be added.  A participant is considered enrolled when they have signed 
the ICF.  If during the screening process a participant fails to fulfill any of the eligibility criteria, 
this will be documented, and the participant will be classified as a screen failure.  Volunteers will 
continue to be screened until 10 participants have completed the study.   
The Principal Investigator (PI) or designee at each site will maintain a master log that will 
correlate each participant ID number to the participant’s name.  The log will remain with the PI  
and will be confidential. 
7.3.2 
Participant Stipend 
Participants will be issued a stipend of 200$ for their participation in the study.  

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7.4 
Eligibility 
The inclusion and exclusion criteria will be reviewed.  Participants are eligible for participation 
in the study if all the inclusion criteria are met and none of the exclusion criteria are met. If the 
participant fails to fulfill any of the eligibility criteria, this will be documented.  The PI or 
designee will sign and date the CRF indicating agreement with the determination of eligibility. 
If the participant fails to fulfill any element of the inclusion and exclusion criteria, the participant 
will be classified as a screen failure and will not be advanced any further into the clinical study. 
7.5 
Baseline Data 
The following demographic information will be obtained and documented on the CRF for all 
enrolled participants:  
Age 
Sex 
Race 
Ethnicity 
Height (inches) 
Weight (pounds) 
Wipe the lateral forehead with an alcohol wipe. Place the 3M SpotOn® zero-heat-flux 
temperature sensor on the participant’s forehead. 
Record the patient temperature (℃) using the 3M SpotOn® zero-heat-flux forehead sensor, the 
Braun ThermoScan 7 tympanic sensor, and an MRI compatible axillary sensor. 
Remove the 3M SpotOn® zero-heat-flux forehead sensor and the Braun ThermoScan 7 tympanic 
sensor before escorting to MRI suite. 
7.6 
Procedure 
7.6.1 
VCool System Set Up 
Attach the disposable delivery tube to the VCool System 
Install the gas inlet filter on the back with the filter bowl vertical (glass side down) 
Attach the air hose to the gas inlet filter 
Connect the power cord to a grounded outlet 
Turn the power switch to “ON” 

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Connect the RS232 cable to the VCool System and to the laptop computer 
Turn on the computer 
Select the following: 
TC-48-20 program. 
COM5 
Communications 
Set Point and set value to -19.0 
Controller options 
Save data to file 
Go to file Explorer, select LabView Data 
Select New and enter participant identification number as file name 
Save data to file 
Turn on gas and set flow meter to 35 liters per minute. 
Confirm temperature is set to -10℃ 
Confirm gas temperature setting at the end of the delivery tube is -5℃ 
Attach nasal cannula to the delivery tube 
7.6.2 
MR Imaging procedure 
• Participants will undergo MRI at the HSF3 research facility at the University of Maryland, 
Baltimore (UIMB). Each imaging session will last approximately 90 minutes. The protocol 
will include high-resolution anatomical MRI for structural reference and tissue segmentation; 
MR Spectroscopy (MRS) to measure metabolite and water resonance frequencies for 
temperature estimation; MR Thermometry to measure phase changes over time to track 
temperature dynamics; Perfusion MRI to measure cerebral blood flow (CBF); as well as 
other structural and functional imaging sequences. These sequences will be repeated at 
multiple time points during the controlled cooling period to monitor temporal changes in 
temperature, perfusion, and tissue properties. 
7.6.3 
Participant Set Up and Monitoring 
Have the participant lie on their back in an inclined position and place the nasal cannula on the 
participant, securing the straps around their head 

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Record the temperature from both temperature sensors and record the time 
Record the flow rate 
Initiate the cooling and record the time.  The induction phase for participant cooling can take up 
to 2 hours. 
Record the core body temperature every 2 minutes from both temperature sensors and record the 
time. The core body temperature is monitored throughout the study. 
If the core body temperature is <35℃ for 5 minutes:  
1.     Remove nasal cannula, if temperature starts to rise after 2 minutes keep cannula off until 
temperature gets back to 35℃. Then reapply nasal cannula and resume treatment. 
2.     If temperature continues to fall below 35℃ after 2 minutes, cover patient with electric 
blanket that has been pre heated on standby. Keep blanket on until temperature gets back 
to 35℃. 
Assess for shivering every 10 minutes using the BSAS. Record the results and time. The BSAS 
is recorded throughout the study. 
Bedside Shivering Assessment Scale  
0 
None 
1 
Mild: Shivering localized to neck/thorax 
2 
Moderate: Intermittent involvement of the upper extremities and/or thorax 
3 
Severe: Generalized shivering or sustained upper and/or lower extremity shivering 
The flow can be increased to 40 liters per minute after 10 minutes 
Record any VCool System adjustments to flow rate or temperature and record the new flow rate 
and temperature and time of adjustment.  Record the reason for the adjustment. 
Assess the participant for adverse events (AEs) throughout the study 
If the participant has a nosebleed, discontinue the study and note the time. 
Monitor patient at first sign of shivering 
▪ 
If Mild, cover patient with regular blanket. 
▪ 
If Moderate or severe – discontinue cooling treatment. 
Continue to record the temperature until either temperature sensor reaches 35.5℃ or the VCool 
System has been used for 2 hours. Note the time the target temperature was achieved.  
If the participant’s core body temperature does not reach 35.5℃ in 2 hours, the study is 
concluded 

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▪ 
Remove the nasal cannula from the participant and dispose of it properly 
▪ 
Monitor the participant’s core body temperature until it returns to baseline.  Blankets 
can be applied to help with warming. 
▪ 
Remove the axillary thermometer 
If the participant’s core body temperature reaches 35.5℃, proceed to the next steps 
Maintain the target temperature of 35.0℃ to 36.0℃ for 1 hour: 
Adjust flow rate by 5 liters per minute from baseline every 2 minutes 
▪ 
If temperature falls below 35℃., reduce flow rate by 5 liters per minute every 2 
minutes until temperature rises back to 35℃ 
▪ 
If temperature rises above 36℃, increase flowrate 5 liters per minute every 2 minutes 
until temp falls below 36℃ 
Remove the nasal cannula and the air delivery tube and dispose of them properly 
Once out of the MRI suite, record the patient temperature (℃) using the 3M SpotOn® zero-heat-
flux forehead sensor, the Braun ThermoScan 7 tympanic sensor 
Monitor the participant’s core body temperature until it returns to baseline.  Blankets can be 
applied to help with warming. 
Remove the 3M SpotOn® zero-heat-flux forehead sensor and the Braun ThermoScan 7 tympanic 
sensor before escorting to MRI suite. 
7.6.4 
VCool System Shut Down 
Turn the power switch on the VCool System to “OFF” 
Turn off the flow meter 
Remove the medical air hose from the flow meter 
Disconnect the power cord 
Wipe the exterior of the VCool System using the provided Caviwipes 
Air delivery tube and cannula are disposable and should be discarded 
8 EARLY PARTICIPANT WITHDRAWAL OR DISCONTINUATION 
Participants may discontinue the study due to consent withdrawal or withdrawal due to an AE.  
The Investigator may elect at any time to discontinue a participant for any reason if such a 
decision is in the participant’s best medical interest or it is determined the participant is not 

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compliant with the protocol.  If a participant discontinues the study for any reason,  or is 
withdrawn by the Investigator, the primary reason for termination or discontinuation should be 
documented on the CRF. 
9 EARLY STUDY END 
If the study is ended prematurely or suspended: 
• The Sponsor or representative will promptly inform the Investigators of the 
termination or suspension and the reasons and inform the regulatory authority(ies) 
(where required by applicable regulatory requirements) 
• The IRBs will be promptly informed and provided with the reasons(s) for termination 
or suspension by the Sponsor or by the Investigator 
If the Investigator (or IRB) terminates or suspends the investigation without prior agreement of 
the Sponsor: 
• The Investigator will promptly inform the Sponsor and the IRB, provide a detailed 
written explanation of the termination or suspension, and, if feasible, designate 
another qualified Investigator to be trained and continue follow-up of already-
enrolled participants.  The new Investigator/site would be requalified by the Sponsor 
or representative.  Participants would be re-consented. 
• The Investigator will inform the institution (where required by applicable regulatory 
requirements 
• The Investigator will promptly inform the participants and ensure appropriate therapy 
and follow-up for the participants 
• The Sponsor or representative will inform the regulatory authority(ies) (where 
required by applicable regulatory requirements) 
10 ADVERSE EVENTS 
The Investigator is responsible for the detection and documentation of events meeting the 
definition of an AE or SAE as provided in this protocol.  Only treatment emergent AEs and 
SAEs, occurring after randomization through the end of the study visits will be recorded.  All 
AEs, including SAEs that occur during the participant’s study participation, must be documented 
in the participant’s source document and CRF.   
10.1 Definition of an Adverse Event 
An adverse event is any untoward medical occurrence, associated with the use of an 
investigational product, whether or not considered related to the investigational product.  An AE 
is any unfavorable and unintended sign, symptom or disease temporally associated with the use 
of an investigational product and does not imply any judgement about causality.  AEs will be 
considered study-related if the event follows a reasonable temporal sequence from a study-

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related procedure or device and could readily have been produced by the study procedure or 
device.   
An event that emerges during treatment having been absent pre-treatment or worsens relative to 
the pre-treatment state should be reported as a TEAE.  
Laboratory or functional test abnormalities generally are not considered AEs unless they are 
associated with clinical signs or symptoms or require medical intervention.  
An AE includes: 
• Exacerbation of a pre-existing illness 
• Increase in frequency or intensity of a pre-existing episodic event or condition 
• Condition detected or diagnosed after investigational product placement even if 
present prior to the start of the study 
• Continuous persistent disease or symptoms present at Baseline that worsen following 
the start of the study 
Adverse events occurring to any study participant during study participation will be reported by 
the site to the study Sponsor or representative by means of the AE CRF.  The AE CRF includes 
severity, seriousness, action taken, causality and outcome of each event.  The Medical Monitor 
will determine if the AE meets the threshold for a Major Adverse Event (MAE), will verify 
UADE status, and will determine the relatedness of the event to the device and/or procedure. 
All adverse events will be coded and summarized by tabulating the number and percentage of 
participants reporting each event (AE, SAE, and UADE) for the safety population.  An AE that 
is related to the device is called an Adverse Device Effect (ADE). 
10.2 Definition of a Serious Adverse Event 
A serious adverse event (SAE) or serious adverse device effect (SADE) is any AE that resulted in 
any of the following outcomes:  

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• Death 
• Life-threatening -the participant was, in the opinion of the Investigator, at immediate 
risk of death from the AE as it occurred 
• Disability or incapacity 
• Inpatient hospitalization* or prolongation of existing hospitalization 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgement, they may jeopardize the participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
• Fetal distress, fetal death, or congenital abnormality 
*Planned hospitalization for an existing condition is not an SAE.  Hospitalization is defined as 
greater than 24 hours in the hospital. 
An SAE that is related to the device is called a serious adverse device effect (SADE). 
10.3 Severity of Adverse Events and Serious Adverse Events 
The severity of each AE or SAE must be assessed by the Investigator or designee. 
• Mild: The AE is transient or causes mild discomfort.  There usually is no 
intervention/therapy required and the AE does not interfere with the participant’s 
normal activities. 
• Moderate: The AE causes some limitation in activity and some assistance may be 
needed.  Treatment for the AE may be needed. 
• Severe: The AE causes marked limitation in activity.  The participant’s usual daily 
activity is interrupted.  The participant may require medical intervention/therapy; 
hospitalization is possible. 
10.4 Outcome of Adverse Events and Serious Adverse Events 
The outcome of each AE and SAE must be noted in the source documents and CRF. 
• Not recovered / not resolved – the event has not improved 
• Recovered / resolved – the participant has recuperated from the event 
• Recovered / resolved with sequelae – the participant has recuperated from the event 
but retained pathological conditions resulting from the event 
• Recovering / resolving – event is improving 

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• Unknown – either not known, not observed, not recorded, or participant refused to 
provide information 
• Fatal – death as a result of the AE 
10.5 
Assessment of Relatedness to Study Product 
The Investigator or designee will assess each AE and SAE for causality based on their best 
medical judgement, the observed symptoms associated with the event, and the available 
information on the investigational product. 
• Not Related: No evidence of any causal relationship with the investigational device or 
trial intervention. 
• Possibly Related: Some evidence to suggest a causal relationship between the AE and 
the investigational device or trial intervention, but other factors may have contributed 
to the event. 
• Probably Related: Evidence suggests a causal relationship with the investigational 
device or trial intervention; the influence of other factors is unlikely. 
• Definitely Related: Evidence suggests a causal relationship to the investigational 
device or trial intervention, i.e., follows a known or suspected pattern of response, or 
is otherwise logically related to the investigational device or trial intervention, and no 
alternative cause is present. 
10.6 Reporting Serious Adverse Events 
Prompt notification of the Sponsor regarding SAEs is essential so that regulatory responsibilities 
and legal obligations can be satisfied.  The Investigator must report SAEs according to the 
following time frames. 
• Initial notification of all SAEs based on the available information must be provided to 
the Sponsor or designee by phone within 24 hours of the investigational site learning 
of the event.  Initial notification within 24 hours of death or life-threatening events is 
extremely important. 
• Follow-up information, when available, must be sent to the Sponsor or designee 
within 48 hours of receipt of the information by the investigational site 
The Investigator must comply with all applicable local regulatory requirements related to 
reporting SAEs to the IRB. 
The Investigator should institute appropriate therapeutic and follow-up measures in accordance 
with good medical practice and should notify the monitor of such actions and record them in the 
participant’s CRF. 

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10.6.1 
Serious Adverse Event Information to Report 
At a minimum, SAE reports must contain the participant ID number, the serious adverse event 
term, onset date, relationship to study product, and a brief description of the event.  Causality 
should be included in the initial report. 
11 POTENTIAL ANTICIPATED ADVERSE EVENTS 
The following potential anticipated AEs are transient and may be associated with use of the 
VCool Intranasal Cooling System:  
• Nosebleed 
• Shivering 
• Irritation of the nasal passages 
• Skin irritation at the site of the cannula 
• Nasal congestion 
11.1 Immediate Post-Procedure Observations 
There are observations that are expected events immediately post-procedure that would be 
expected with any procedure.  Any event that does not require medical management will not be 
considered significant but will be documented and reported. 
11.2 Unanticipated Adverse Device Effect 
An Unanticipated Adverse Device Effect (UADE) is any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with use of the VCool 
device, if that effect, problem, or death is not identified in nature, severity, or degree of incidence 
in this Investigational Plan (protocol) or any other unanticipated serious problem associated with 
the VCool device that relates to the rights, safety, or welfare of the participants participating in 
this study. 
11.3 Reporting 
All AEs, UADEs, and SAEs will be reported via the CRFs.  All AEs meeting the above 
definitions of an UADE and/or SAE, whether device-related or not, must also be reported to the 
study Sponsor within 24 hours of discovery and to the approving IRB as soon as possible, based 
on IRB requirements but in no event later than 10 working days after the Investigator first learns 
of the AE or effect. 

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12 DATA ANALYSIS 
12.1 Primary Analysis 
The time and flow rate that is required to reduce and maintain each participant’s core 
temperature to 35.5℃ from measured baseline temperature will be calculated. The total number 
of participants who reach the target temperature in 2 hours or less will be calculated. 
12.2 Secondary Analysis 
The incidence of any shivering will be analyzed using the BSAS. The incidence and nature of 
any adverse events or participant intolerance will be tabulated. 
12.3 Populations for Analysis 
The study population will consist of 10 healthy volunteers who have signed the ICF and who 
meet all the inclusion criteria and none of the exclusion criteria. 
12.4 Imaging Data analysis 
All MRI data will be spatially aligned to the structural images to ensure accurate anatomical 
localization of measurements. Spectroscopic data will be reconstructed to obtain resonance 
frequencies for water and metabolites (N-acetylaspartate, choline, creatine). Temperature will be 
estimated based on the chemical shift difference between the water peak and metabolite peaks, 
which is temperature-dependent. Phase images from the thermometry acquisition will be 
unwrapped and converted to temperature change maps using the proton resonance frequency 
(PRF) shift method. These maps will capture dynamic temperature changes over the cooling 
period. CBF maps will be generated using standard perfusion modeling (e.g., ASL kinetic 
modeling) to quantify cerebral blood flow. Temporal changes in CBF will be evaluated across 
the cooling period. Imaging-derived measures (temperature, Δtemperature, CBF) will be 
extracted from predefined anatomical regions of interest or whole-brain parcellations to 
characterize regional variability in cooling response.  
13 RESPONSIBILITIES 
The PI or designee must ensure and maintain adequate and accurate records of all observations 
and other data pertinent to the clinical study for each study participant.  The PI or designee will 
make all appropriate safety assessments on an ongoing basis.  The PI or designee will prepare 
and maintain adequate and accurate study source documents (medical records, AE, raw data 
collection forms, etc.) designed to record all observations and other pertinent data for each 
participant.  The PI will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors, and the IRB to have direct access to all documents pertaining to the study. 
13.1 Data Quality Assurance 
Standardized paper CRFs will be used at the investigational site.  The PI is responsible for 
ensuring completion and timely submission of the forms to the study Sponsor or designee for 
data processing.  All data are reviewed to identify inconsistent or missing data and AEs.  All 

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hard copy forms will be secured to ensure confidentiality.  The PI is required to maintain all 
source documents as required by the protocol, including any applicable supporting medical 
records and Informed Consents.  The source documents may be reviewed to verify information 
submitted on the CRFs. 
13.2 Protocol Deviations 
All protocol deviations (i.e., instance[s] of failure to follow, intentionally or unintentionally, the 
requirements of this protocol) must be documented in the appropriate Protocol Deviation CRF 
with an explanation for the deviation.  
The Sponsor or representative is responsible for assessing protocol deviations in an ongoing 
manner and determining their impact on the conduct of the study.  After evaluation of each 
deviation, the Sponsor or representative will determine if corrective and preventive actions need 
to occur.  
Minor Deviations: A minor deviation does not impact the participants’ rights, safety, or well-
being, or the completeness, accuracy, or reliability of the study data.  Minor deviations shall be 
documented in the study database along with a full description of the event and outcome.  The 
Sponsor will analyze these deviations and assess their significance.  
Major Deviations: A major deviation is a deviation from the protocol that may impact the 
participants’ rights, safety, or well-being, or the completeness, accuracy or reliability of the study 
data related to key endpoints, or a significant deviation from national or local regulations or IRB 
guidelines.  Major deviations should be reported to the Sponsor within 48 hours of site awareness 
of the event and must be documented in the study database along with a full description of the 
event and outcome.  The Sponsor will analyze these deviations and assess their significance.  
Major protocol deviations should be reported to the IRBs and the regulatory authorities as per 
national or local regulations. 
14 PARTICIPANTS LOST TO FOLLOW-UP 
Participants will be followed up for 24 hours for any unresolved adverse events.  A participant 
will be considered lost to follow-up if reasonable efforts made to contact the participant have 
failed.  At least three separate attempts should be made to contact the participant.  All attempts to 
contact the participant will be documented with the last attempt made via registered mail.   
15 INSTITUTIONAL REVIEW BOARD 
Requirements for institutional review as set forth in Title 21 of the Code of Federal Regulations 
(21 CFR) or other relevant local regulations for institutional review will be followed.  The 
Investigational Plan (Protocol), Informed Consent and other required documents must be 
approved by the IRB before enrollment of participants in the study.  The Sponsor or 
representative must confirm that the IRB is in compliance with the general standards for the 
composition, operation, and responsibility of an IRB as set forth in ICH Guidelines for GCP, 
Sections 3.1 to 3.4, and 21 CFR, Part 56.  Any member of the IRB who is directly affiliated with 

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this study as an Investigator or as site personnel must abstain from the IRB vote on the approval 
of the protocol.  The PI, in collaboration with the Sponsor or representative, will be responsible 
for reporting to the IRB all changes in research activity, including protocol amendments, safety 
reports, all unanticipated problems involving risks to participants, and study termination.  The 
PI or delegate will also be responsible for submitting progress reports to the IRB at regular 
intervals appropriate to the degree of patient risk involved, but no less than once per year as 
required by the IRB.  Copies of all IRB notifications and approvals will be forwarded to the 
Sponsor or representative. 
16 INVESTIGATOR REPORTS 
The PI will be responsible for the following reports: 
• AEs: SAEs, SADEs, and UADEs shall be reported to the Sponsor by fax or email 
within 24 hours of the Investigator becoming aware of the event 
• All other AEs will be reported to the Sponsor via the Adverse Event CRF. 
• AEs must also be reported to the reviewing IRB in compliance with its reporting 
requirements.  For serious adverse events (whether or not device-related), this is 
typically no later than 10 business days of the Investigator becoming aware of the 
event. 
• An Investigator shall submit to the reviewing IRB a report of any UADE occurring 
during an investigation as soon as possible, but in no event later than 10 working days 
after the Investigator first learns of the effect 
• Protocol Deviations: The Investigator is responsible for reporting all protocol 
deviations to the Sponsor and to the IRB in compliance with the IRB’s reporting 
requirements.  The Sponsor will provide a deviation log and CRF to document 
protocol deviations. 
• Withdrawal of IRB Approval: The Investigator shall report to the Sponsor within 5 
working days if, for any reason, the IRB withdraws approval to conduct the 
investigation.  The report will include a complete description of the reason(s) for 
which approval was withdrawn. 
Other Reports: Upon request of the Sponsor, the FDA, or the IRB, the Investigator shall provide 
accurate, complete, and current information. 
17 TRAINING 
The Sponsor or representative will train all site staff on the device, protocol, and study 
procedures in accordance with their responsibilities. 
As necessary, training will occur after any revisions to the device, Instructions for Use (IFU), 
protocol, or study procedures. 

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18 STUDY DEVICE ACCOUNTABILITY 
The Investigator or designated site staff must maintain device accountability records throughout 
the course of the study.  The PI will not supply the investigational device to other Investigators not 
participating in the study and the investigational device will be used only on consented 
participants as directed by this protocol.  Use of the VCool Intranasal Cooling System, other than 
as directed by this protocol, is not allowed. 
Device accountability will indicate receipt, use, and final disposition of each device.  The 
Investigator or designee will complete a device accountability CRF. 
19 ETHICS/PROTECTION OF HUMAN PARTICIPANTS 
19.1 Ethical Conduct of the Study 
The study will be conducted in compliance with the ICH Guidelines on GCP, 21 CFR 812 and 
ISO14155 Standards. 
19.2 Participant Confidentiality 
All clinical study findings and documents will be regarded as confidential.  Study documents 
(protocols and other material) will be stored appropriately to ensure their confidentiality.  
Investigator and members of their research team (including the IRB) must not disclose such 
information without prior written approval from the Sponsor, except to the extent necessary to 
obtain informed consent from participants who wish to participate in the trial or to comply with 
regulatory requirements.  The anonymity of participating participants must be maintained.  
Participants will be specified on study documents by their unique number and initials, not by 
name.  Documents that identify the participant (e.g., the signed informed consent document) 
must be maintained in confidence by the Investigator. 
20 ADMINISTRATIVE CONSIDERATIONS 
20.1 Protocol Approval and Amendment(s) 
No modifications to the protocol may be made without the written consent of the Sponsor.  To 
alter the protocol, amendments must be written, released by the Sponsor, and approved by the 
IRB prior to implementation (as appropriate).  Administrative protocol changes or protocol 
clarifications may be made without the need for a formal amendment, but these changes will be 
documented in an integrated clinical study report. 
20.2 Case Report Form Completion 
A Case Report Form (CRF) must be completed for every participant that signs an ICF.  Either 
the PI or sub-investigator must sign and date the completed CRF within a reasonable time period 
after completion of data collection.  If a participant does not complete the study, the reason for 
withdrawal must be documented. 

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The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported.  All data collection should be completed in a neat, legible manner to ensure 
accurate interpretation of data. 
Data collection and accurate documentation are the responsibility of the study staff under 
 
the supervision of the investigator.  Data recorded on paper must use black ink and any 
changes or corrections made must be done by drawing a single line through the original entry.  
The corrected entry must be initialed and dated by the individual making the corrections and 
provide a reason for the change. DO NOT ERASE, OVERWRITE, OR USE CORRECTION 
FLUID OR TAPE ON THE ORIGINAL.   
20.3 Archiving Study Documents 
The PI shall maintain the records for this study for a period of 2 years after the latter of the 
following 2 dates: the date on which the investigation is terminated or completed, or the date that 
the records are no longer required for purposes of supporting a premarket approval application, a 
premarket notification submission, or a request for De Novo classification. 
The Investigator will notify the Sponsor in the event he/she relocates, or for any reason desires to 
dispose of the records.  
All source documents must be retained.  Source documents (paper or electronic) are the original 
records of clinical findings, observations, or other activities in a clinical study necessary for the 
reconstruction and evaluation of that trial.  Examples of source documents include but are not 
limited to hospital and clinic medical records, signed informed consent forms, evaluation 
checklists, scan or laboratory results, etc. 
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