Wingate-type Exercise Test to Evaluate the Effect of High Velocity Therapy on Recovery Sensation and Blood Lactate Decline
Phase: NA
Conditions: Dyspnea, Lactic Acidosis, Muscle, Breathlessness, Exercise, Recovery
Sponsor: Vapotherm, Inc.

Wingate-type Exercise Test to evaluate the effect of High Velocity Therapy on 
Recovery Sensation and Blood Lactate Decline
NCT05984186 
28 SEP 2022 

   
Protocol Title: 
Wingate-type Exercise Test to evaluate the effect of High 
Velocity Therapy on Recovery Sensation and Blood Lactate 
Decline  
  
Protocol Number: 
 
RP-VTPF2022001Sci  
  
  
Revision: 
 
 
Rev 1.0  
  
  
Principal Investigator: 
Dr. L. Bruce Gladden  
  
Co-Investigators: 
 
Dr. Michael Roberts  
Dr. Jessica Whittle  
  
  
Sponsor: 
 
 
Vapotherm, Inc  
100 Domain Drive  
Exeter, NH  03833  
1 (603) 658-0011  
http://www.vtherm.com  
  
  
  
  
  
  
  
  
  
  
Confidential  
  
Study site should keep protocol, all contents and related information confidential.  
  
  
 
 
 

Protocol Approval  
  
  
Investigator Statement  
  
As Investigator of the study titled Wingate-type Exercise Test to evaluate the effect of High 
Velocity Therapy on Recovery Sensation and Blood Lactate Decline (the “Study”), I agree to:   
  
(i) conduct the Study in accordance with: this Investigator Agreement; the Study’s Protocol as 
approved by the IRB (the “Protocol”); all applicable laws and regulations; and any IRB or FDA 
conditions of approval;    
(ii) await IRB approval for the Protocol before obtaining informed consents (if applicable);  
(iii) ensure that all requirements for informed consent are met and not allow any participant to 
participate in the Study before obtaining that participant’s informed consent (if applicable);   
(iv) not make modifications to the Protocol without first obtaining consensus from the Vapotherm 
Science and Innovation team and necessary IRB approval;   
(v) maintain Study documentation for the period of time as required by appropriate regulations; 
and  
(vi) supply to the Sponsor, as part of this Investigator Agreement, my curriculum vitae.  
  
  
INVESTIGATOR 
 
 
 
 
  
  
Signature: 
_________________________________________________  
  
Printed Name:    L. Bruce Gladden____________________________ 
  
Date:  
____________________ 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 

 
Glossary of Definitions and Terms  
   
High Velocity Therapy (HVT): The use of a medical device to deliver ideally humidified, heated gas 
through a small bore nasal cannula to augment ventilation and breathing. 
 
Work of Breathing (WOB)/Recovery Sensation:  The physical, physiologic muscular demands of 
breathing and exercise recovery manifested through the sign and symptoms of increased physical 
exertion.  
  
Respiratory Rate (RR): The number of breaths a participant takes per minute (breaths·min-1).  
  
Heart Rate (HR): The number of heart beats per minute (beats·min-1).  
  
BORG Score: a rating scale (1-10) for perceived level of exertion 
  
  
 I. Background and Significance  
  
Vapotherm high velocity therapy (HVT) creates ideally conditioned respiratory gas and delivers it 
nasally, supporting spontaneous ventilation. This differs from simple oxygen therapy in that the gas 
is heated, humidified, an exchange of all gasses, including CO2, is enhanced. 1,2.  Vapotherm 
technology is unique in its ability to provide this conditioned gas through a small-prong nasal 
cannula resulting in a high velocity without the well-known adverse effects related to drying and 
cooling of the nasal mucosa 3.  This high velocity nasal flow facilitates a well described mechanism 
of improving ventilatory efficiency by way of eliminating anatomical dead space of the upper 
airway 2.    
  
The purging of the nasal cavity is important to alveolar gas exchange because the gas that is drawn 
to the respiratory regions of the lungs comes from the anatomical reservoir created by the flush, in 
the same way that oxygen conservation masks can incorporate reservoir bags to reduce the bulk 
flow requirements from the oxygen source to achieve the same oxygenation effect 2,4.  Based on 
mathematical modeling, physiologic studies and clinical observations flow rates of 25 to 35 L·min-1 
through Vapotherm’s adult cannula purges the anatomical reservoir of the upper airway in the 
window of time between breaths.  Vapotherm’s humidification systems are specifically designed to 
tolerate a high back pressure in the humidification cartridge that is generated by passing these flow 
rates through small bore cannula resulting in the appropriate flow velocities (turbulent energy) 4.  
  
Since 2000, HVT has been used extensively and has been well studied. 2-6 This study is intended as a 
pilot study utilizing a Wingate-type Exercise Test18 to evaluate the impact of HVT on reduction of 
work of breathing and improvement of lactate clearance rate during exercise and the recovery 
interval. This work may provide foundational data for a larger study and may identify the 
appropriate parameters for evaluation of physical rehab patients. 
 
 
II. Overall Study Objective  
  
The overall objective of this study is to evaluate the impact of HVT on reduction of work of 
breathing and change in lactate clearance rate during exercise and recovery during a Wingate-type 
Exercise test. The study will include four study segments, corresponding to four therapy settings 

being tested: (1) FiO2=100% with Flow=5LPM, (2) FiO2=21% with Flow=25-30LPM, (3) 
FiO2=100% with Flow=25-30LPM, (4) FiO2=21% with Flow=5LPM.  
  
The hypothesis is that HVT, regardless of the oxygen concentration (i.e., FiO2), will reduce the 
work of breathing and increase the lactate clearance rate during exercise and recovery intervals.   
  
To test this hypothesis, the study will be conducted with the following specific aims:  
  
Aim #1:  Primary Outcome.   
The primary endpoint is change in blood lactate from before the exercise test to recovery over a 
period of 30-60 minutes post-exercise. 
  
Aim #2:  Secondary Outcomes.   
The secondary endpoints evaluate additional data that may be clinically meaningful. Data will 
include vital signs (SpO2, heart rate [HR], respiratory rate [RR], blood pressure [BP]), and 
perceived level of exertion (BORG [score 0-10]), as measured during the exercise and recovery 
intervals. Work performance will be computed during test period only, including peak power 
output, mean power output over 30second intervals, and decrease in power.    
  
Aim #3:  Tertiary Outcomes.   
The tertiary endpoints will evaluate the participant perceptions of the therapy impact during study 
procedures: (1) Level of Exertion at Exercise End, (2) Relief of Exertion Recovery End, (3) 
Comfort/Tolerance of Therapy at Study End [exercise and recovery], as measured on a 1-10 Likert 
scale.   
1. 
Level of Exertion at Exercise End: “How tired do you feel?”  
2. 
Relief of Exertion at Recovery End: “How fast do you feel you recovered?”  
3. 
Comfort/Tolerance of Therapy at Therapy Segment End: “How comfortable 
was the therapy while you had it on during exercise? How comfortable was the 
therapy while you had it on during recovery?   
  
  
These endpoints will establish the effect of Vapotherm HVNI on lactate clearance, work of 
breathing, and perceived exertion during exercise and recovery intervals.  
  
   
III. Participant Selection  
Participants will be identified and recruited by study investigators.  The study will take place in an 
appropriate educational forum (e.g., hospital, academic center, laboratory setting, etc.) where 
kinesiology testing can be accomplished.  Initial contact will be made by study investigators, and 
volunteers may include any interested participants.  Participants will be compensated for their time 
at a rate of approximately $50 per hour.   
  
Inclusion Criteria  
1. Adults over 18 years old, in a general state of good health, of either sex  
2. No known contraindication to performing a maximal exercise test, i.e., Wingate-type 
Anaerobic exercise test  
3. Participants must consider themselves able to perform “regular moderate” or 
“regular strenuous” exercise.   

a. “Regular moderate” exercise includes less than 30 minutes every day or 30 
minutes every other day, of some form of deliberate exercise, that does not 
include walking. 7   
b. “Regular strenuous” exercise is 30+ minutes per day, of some form of 
deliberate exercise, that does not include walking. 7   
  
Exclusion Criteria  
1. Not considered a ‘high-performance athlete’   
2. Known active cardiovascular, metabolic, liver, or renal disease 8,9  
3. Orthopedic limitations to exercise 10  
4. Pregnancy 10  
5. Use of beta-blockers or beta-agonist asthma medications 10  
7. Exercise induced asthma  
8. Any other health-related issue that would involve the participant’s fitness 
capability   
9. Inability to complete all of the study procedures  
  
  
IV. Study Design  
The feasibility/pilot study will be performed as a prospective, unblinded clinical trial of a Wingate-
type Anaerobic exercise test. Submaximal cycle ergometry tests are routinely used in exercise, 
kinesiology, and rehabilitation facilities, typically without physician supervision, to assess fitness 
level and/or physiologic response to exercise and pose minimal risk.  The study will take place in an 
exercise kinesiology and rehabilitation laboratory facility setting.   
  
The study is a repeated measures model that will collect data on the participants with the 
designated HVT at four specified settings (Flow/FiO2) during the Wingate exercise test and during 
the recovery interval. The Wingate exercise test configuration, equipment and procedures will be 
repeated for each HVT setting for a matched dataset. Participants who fit criteria will be asked to 
consent to enroll in the study.   
  
The study will include four study arms, corresponding to four therapy settings being tested: (1) 
FiO2=100% with Flow=5LPM, (2) FiO2=21% with Flow=25-30LPM, (3) FiO2=100% with Flow=25-
30LPM, (4) FiO2=21% with Flow=5LPM. The participants will wear the appropriately sized nasal 
cannula interface during the exercise and recovery.   
  
V. Participant Enrollment 
  
Participants will be solicited by investigators and consented prior to participation.   Once 
consented, participants will be scheduled for their testing session(s) per protocol procedures.  If 
enrolled, participants will be randomized to the order of the different settings on the HVT 2.0 
device in different test sessions. Each participant will present on 4 different days for testing. This is 
to avoid fatigue related changes in sequential tests. Additional testing sessions may be scheduled to 
complete data collection if needed.   
  
Sample Size:  
Because no data exist for variance around these parameters, we will plan to enroll 15 
participants, each to perform 4 test sessions. 
  
Data Safety Monitoring:  

Given that this protocol is a conventional exercise test protocol and therefore very low 
risk and routinely performed without physician oversight, there is no plan for a Data 
Safety Monitoring Board.  Any adverse events (AE) will be promptly reported to the IRB 
for consideration.    
  
  
VI. Study Procedures  
  
Screening, Enrollment, & Management  
During screening, participants will be asked to participate in this study, and if so, they will provide 
informed consent prior to enrollment. Participants will be instructed that if at any time during the 
study that they wish to discontinue the study, they are free to stop the testing and discontinue 
study participation at any time. All study procedures will be explained to the participant prior to 
starting any procedures, and all participants will be given a copy of the informed consent form.   
  
Participants will be scheduled for test sessions to complete the objectives of the study and 
instructed to wear exercise appropriate clothing.  Participants will be informed that prior to each 
test session, they should abstain from caffeine or tobacco products for a minimum of 4-hours, and 
alcohol and strenuous exercise for 10-hours 10.  Participants are instructed that if at any time during 
the study he/she feels faint, dizzy, short of breath, or for any reason, they should stop the test.   
  
Data collection during enrollment will include participant demographics (e.g., age, sex, height, 
weight).  At each session, participant vital signs, lactate levels, dyspnea scores, work performance 
indices, and perception scores will be collected. The study will include four sessions, corresponding 
to four therapy settings being tested: (1) FiO2=100% with Flow=5LPM, (2) FiO2=21% with 
Flow=25-30LPM, (3) FiO2=100% with Flow=25-30LPM, (4) FiO2=21% with Flow=5LPM.  
 
For each test session of the four HVT Settings, the following procedures will be followed.   
  
Pre-Test Preparations:  
Prior to starting the test, the participant will perform 2-3 second warm up sprints to acclimate to 
the ergometer. The cycle ergometer seating settings will be maintained consistent across all four 
therapy settings. Participants will be instrumented appropriately and initial data (e.g., vital signs, 
lactate, dyspnea) will be collected for baseline.   
  
Wingate-type Exercise Test Procedures:  
The exercise test model is called the Wingate anaerobic test. In a pre-test, the participants will 
Wingate test consists of pedaling with maximal effort for a series of short 8-second intervals 
against different loads, separated by 5 min of rest. This pre-testing is done to determine the load 
required for maximal power output. For the actual Wingate-type test, the participant will pedal as 
rapidly as possible for 60 sec against the load determined for maximal power output. Three 
indices of performance will be computed during the test period – peak power output, mean 
power output over the 60 seconds, and decrease in power (fatigue index).    
  
At end of exercise interval, participant will be asked their perception of their level of exertion.  
  
Recovery Interval:  

Recovery interval will take place after exercise period up to 1 hour, or until participant is fully 
recovered and lactate levels approach baseline. A minimum of 15 samples during the recovery 
interval will be performed to complete lactate recovery data evaluation.   
  
At end of recovery interval, participant perception of (1) Relief of Exertion at Recovery End, and 
(2) Comfort/Tolerance of Therapy will be recorded. 
   
Sessions will be repeated on separate days, scheduled at the convenience of participant and 
laboratory, until a participant has completed a session at each of the HVT setting levels. 
   
VII. Data Collection  
  
Table 1. Key study data and collection points for each Phase of the Study.  
 
Study 
Start  
After 
Warm-Up  
Exercise Period 
q60sec  
Recovery 
Period q5min  
Study 
End  
Participant pertinent Medical 
History  
X  
  
  
  
  
Participant Vitals * (HR, RR, SpO2, 
BP)  
X  
X  
X  
X  
  
Lactate [La-]  
X  
X  
X  
X  
  
Dyspnea (Borg scale)  
X  
X  
X  
X  
  
Perception Scores (1-10 scale)  
  
  
  
  
X  
Work Performance  
  
  
X  
  
  
*Vitals only measured prior to start of exercise, after exercise period ends, and after recovery 
interval. If practical, may record real-time the HR, RR, and SpO2 with digital sensors. This will 
be completed for each Therapy Settings designated in the Study Protocol.   
  
Data collection during enrollment will include participant demographics (e.g., age, gender, height, 
weight).  Each Therapy Settings will collect the relevant participant vitals, lactate levels, dyspnea 
scores, and perception scores.   
 
Primary Endpoint  
• 
Change in lactate over (1) the exercise test interval, and (2) the recovery interval  
  
Secondary Endpoints  
• 
Participant Vitals: HR, RR, SpO2, BP  
• 
Dyspnea Score: modified BORG score, 1-10 scale  
• 
Exercise Test Work Performance: peak power output, mean power output over 60 
seconds, and decrease in power (fatigue index)  
  
Tertiary Endpoint  
Participant Perception of Performance/Recovery [1-10 scale]  
• 
Level of Exertion at Exercise End: “How tired do you feel?”  
• 
Relief of Exertion at Recovery End: “How fast do you feel you recovered?”  

• 
Comfort/Tolerance of Therapy at Therapy Segment End: “How comfortable was the 
therapy while you had it on during exercise? How comfortable was the therapy 
while you had it on during recovery?   
  
VIII. Statistical Analysis  
Participant demographics and characteristics will be summarized, compared, and appropriate 
statistical testing will be performed for the continuous and categorical variables. Descriptive 
analyses of the primary endpoints, supporting data/variables, and secondary outcome data will be 
performed.  Assuming a non-normal data distribution for this study, a non-parametric test (e.g., 
Wilcoxon Signed Rank Sum test) will be performed with significance interval of 0.05 on all 
applicable variables. If continuous variables present a normal distribution, between-trial 
comparisons will be performed using two-way (within-within; trial* post-exercise sampling times) 
repeated measures ANOVAs.  Otherwise, for the categorical variables, the Fisher’s Exact test will be 
performed. Further analyses may be performed on the collected data based on ongoing analyses at 
time of study completion to identify additional relevant results.  
  
IX. Risks and Discomforts  
There are minimal or no known risks to the Wingate Anaerobic Exercise Test.12,13 Use of the high 
flow nasal cannula therapy by healthy persons has no known risks and has been used in the clinical 
setting for approximately seventeen years without known reports of adverse events related to the 
administration of high nasal flows when used according to manufacturer’s recommendations. Prior 
work indicates that approximately ≤ 4 cmH2O of distending pressure may be generated in the upper 
airway 14,15 which is well below any known threshold for injury.  In addition, it has been 
demonstrated that delivery of high flows of conditioned gas from a nasal cannula has a positive 
effect on airway mucosal function 16,17.  Blood lactate measurements will be made using 1-2cc of 
whole blood from finger sticks (similar to blood glucose measurements using a glucometer). 
Fingers will be wiped with alcohol pads prior to sticking and sterile capillary tubes will be used for 
each sample. Alternatively, blood samples will be collected from a venous catheter in a prominent 
arm vein for enzymatic and/or lactate meter measurement of blood lactate concentration. 
  
For these reasons, we have determined that this study represents a minimal risk and discomfort to 
the participants. The is the expected discomfort related to standard exercise and performance 
testing in exercise physiology laboratories. 
  
X. Potential Benefits  
Participants will receive no direct health benefit from participation. The trial may result in 
knowledge that leads to improvements in the quality of care, participant experience and ultimately 
cost of care associated with the care for participant with respiratory disease or those needed 
physical rehabilitation. Participants may receive up to $50 per hour for participation, paid at the 
end of their participation.   
  
XI. Monitoring and Quality Assurance  
The clinical trial site will be monitored in accordance with policies at Vapotherm and those federal 
regulations that pertain to clinical research, namely 21 CFR Parts 50, 54, 56 and 812 and others as 
applicable.  Monitoring will occur at regular frequency by the PI or designee, such as to allow 
ongoing review of data collected, site qualifications and compliance with the protocol.  All 
investigators and study staff will be appropriately trained to ensure compliance with the protocol.   
  
XII. Protocol Deviations  

Any deviations from the Data Collection plan identified during monitoring or through other means 
will be documented on appropriate case report forms. These deviations include, but are not limited 
to items such as the following:   
• 
Deviation from procedural sequencing, per protocol  
• 
Failure to complete initial participant data collection   
• 
Failure to capture/record physiologic readings at required/prescribed intervals  
If the study site demonstrates a pattern of consistent and frequent deviations, the Sponsor will 
undertake appropriate activities (e.g., re-training) to attempt to bring the site into compliance with 
the protocol. A pattern of repeated serious deviations from the protocol may result in site 
termination from the study.  
  
XIII. Adverse Event Reporting  
During the course of the participant’s participation in the study, the investigator will determine 
whether any adverse events have occurred.  For the purposes of this protocol, an adverse event is 
any undesirable clinical/medical occurrence in a participant that is or is not attributed to the device 
or procedure required by this protocol.  If any adverse event occurs, either anticipated or 
unanticipated, the investigators will immediately contact the sponsor’s representative (site 
monitor) indicated on page 1.  
  
XIV. Confidentiality  
Rigorous procedures will be followed to maintain confidentiality of participant identification and 
test-related information and to adhere to government regulations concerning privacy.  The privacy 
rules and requirements according to governing regulations will be adhered to.  Participants will be 
assigned a study ID number. Only the data collection form and medical history form will 
link the participant's name to their ID number. These forms, along with consent forms, will be 
locked in Dr. Gladden's office and will only be accessed by him or involved study personnel. 
Assigning participant ID numbers and aliases to participant names on data collection and medical 
history forms will be performed in order to facilitate testing procedures. 
 
When data collection is complete, all linking information to participant identity will be destroyed. 
 
All Vapotherm representatives involved in this study will only have access to the participants’ 
unique identification number throughout the study.    
  
Confidentiality will be protected and maintained to the extent allowed by law.  
                                                                                                                                                                                                 
                                                                                                                              
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Ayalon A, Inbar 0, Bar-Or 0. Relationships among measurements of explosive strength and 
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