Kinetic Anesthesia Device for Lidocaine Injection: a Randomized Split-body Study of the Effects of Kinetic Anesthesia Devices on Pain of Lidocaine Injection in Healthy Volunteers
Phase: NA
Conditions: Local Anaesthetic Complication, Pain
Sponsor: University of Pennsylvania

 
 
  
 
 
Kinetic Anesthesia Device for Lidocaine Injection: a randomized split-body study of the effects of 
kinetic anesthesia devices on pain of lidocaine injection in healthy volunteers. 
 
 
 
Principal Investigator (1) 
SOBANKO, JOSEPH F 
4212 - DE-Dermatology 
Perelman Center for Advanced Medici 
Division of Dermatologic Surgery an 
3400 Civic Center Boulevard 
 Philadelphia PA 19104-0000 
215-662-6534 
Joseph.Sobanko@uphs.upenn.edu 
HS Training Completed: Yes 
Training Expiration Date: 05/29/2020 
Name of course completed : CITI Protection of Human Subjects 
Research Training - ORA 
NIH Grant Number                         
 
Include NIH grant number if applicable   
 
Investigational Product: 
 
Blaine Labs Vibration Anesthesia Device 
 
IRB Number: 
828686 
 
 
 
 

ii 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
Table of Contents 
 
Contents 
LIST OF ABBREVIATIONS ....................................................................................................................... VII 
STUDY SUMMARY ....................................................................................................................................... 1 
BACKGROUND AND STUDY RATIONALE ................................................................................................ 3 
INTRODUCTION ............................................................................................................................................ 3 
1.1 
BACKGROUND AND RELEVANT LITERATURE ...................................................................................... 3 
1.2 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL PRODUCT ........................................................... 4 
1.2.1 
Nonclinical Data ....................................................................................................................... 3 
2 
STUDY OBJECTIVES .......................................................................................................................... 4 
2.1 
PRIMARY OBJECTIVE ....................................................................................................................... 4 
2.2 
SECONDARY OBJECTIVES (IF APPLICABLE) ....................................................................................... 4 
3 
INVESTIGATIONAL PLAN ................................................................................................................... 5 
3.1 
GENERAL DESIGN ........................................................................................................................... 5 
3.1.1 
Screening Phase ...................................................................................................................... 5 
3.1.2 
Study Intervention Phase ......................................................................................................... 5 
3.1.3 
Phase II (if applicable include and add details about open label study phase if appropriate) . 5 
 
3.2 
STUDY ENDPOINTS ......................................................................................................................... 6 
3.2.1 
Primary Study Endpoints.......................................................................................................... 6 
3.2.2 
Secondary Study Endpoints ..................................................................................................... 6 
4 
STUDY POPULATION AND DURATION OF PARTICIPATION ......................................................... 6 
4.1 
INCLUSION/EXCLUSION CRITERIA ..................................................................................................... 6 
4.2 
INCLUSION CRITERIA ....................................................................................................................... 6 
4.3 
EXCLUSION CRITERIA ...................................................................................................................... 7 
4.4 
SUBJECT RECRUITMENT .................................................................................................................. 7 
4.5 
DURATION OF STUDY PARTICIPATION ............................................................................................... 7 
4.6 
TOTAL NUMBER OF SUBJECTS AND SITES: ........................................................................................ 7 
    4.7        Vulnerable Populations………………………………………………………………………………… 7 
5 
STUDY INTERVENTION (STUDY DRUG, DEVICE, BIOLOGIC, VACCINE, FOOD ETC.) ............... 7 
5.1 
DESCRIPTION.................................................................................................................................. 7 
 
5.2 
RECEIPT ......................................................................................................................................... 7 
6 
STUDY PROCEDURES ........................................................................................................................ 7 
EXAMPLE: TABLE 1: SCHEDULE OF STUDY PROCEDURES .............................................................. 10 
6.1 
STUDY INTERVENTION PHASE .......................................................................................................... 8 
6.2 
SUBJECT WITHDRAWAL ................................................................................................................... 8 
7 
STUDY EVALUATIONS AND MEASUREMENTS .............................................................................. 8 
7.1 
VITAL SIGNS ................................................................................................................................. 13 
8 
STATISTICAL PLAN ............................................................................................................................ 9 
8.1 
PRIMARY ENDPOINT ........................................................................................................................ 9 
8.2 
SECONDARY ENDPOINTS ................................................................................................................. 9 
8.3 
SAMPLE SIZE AND POWER DETERMINATION ..................................................................................... 9 
8.4 
STATISTICAL METHODS ................................................................................................................... 9 
9 
SAFETY AND ADVERSE EVENTS ................................................................................................... 10 

iii 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
9.1 
DEFINITIONS ................................................................................................................................. 10 
9.1.1 
Adverse Event ........................................................................................................................ 10 
9.1.2 
Serious Adverse Event........................................................................................................... 10 
9.2 
RECORDING OF ADVERSE EVENTS ................................................................................................. 10 
9.3 
RELATIONSHIP OF SAE TO STUDY ................................................................................................. 11 
9.4 
REPORTING OF SERIOUS ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND UNANTICIPATED 
PROBLEMS ................................................................................................................................................ 11 
9.4.1 
Follow-up report ..................................................................................................................... 11 
9.4.2 
Investigator reporting: notifying the study sponsor ................................................................ 17 
10 
STUDY ADMINISTRATION, DATA HANDLING AND RECORD KEEPING .................................... 11 
10.1 
CONFIDENTIALITY.......................................................................................................................... 11 
10.2 
DATA COLLECTION AND MANAGEMENT .......................................................................................... 12 
11 
ETHICAL CONSIDERATIONS ........................................................................................................... 12 
11.1 
RISKS ........................................................................................................................................... 12 
11.2 
BENEFITS ..................................................................................................................................... 13 
11.3 
RISK BENEFIT ASSESSMENT .......................................................................................................... 13 
11.4 
INFORMED CONSENT PROCESS / HIPAA AUTHORIZATION............................................................... 13 
12 
REFERENCES .................................................................................................................................... 13 
13 
ATTACHMENTS ................................................................................................................................. 13 
 
 
 
 

Kinetic Anesthesia Device Study 
Version 3: 11/30/2017 
 
Study Summary 
Title 
Kinetic Anesthesia Device for Lidocaine Injection: a randomized split-body 
study of the effects of kinetic anesthesia devices on pain of lidocaine injection 
in healthy volunteers. 
Short Title 
Kinetic Anesthesia Device Study 
IRB Number 
Pending   
Protocol 
Number 
Pending 
Phase 
Not applicable  
Methodology 
open label split-body crossover trial with randomization of subjects to one of three 
injection locations, and randomization of the order of injection with and without 
intervention. 
Study 
Duration 
Recruitment and enrollment period: 2 months  
Subjects' length of participation in the study: 1 visit.  
The entire encounter should take less than one hour.  
Project date of the proposed study: Recruitment and enrollment will commence with 
IRB approval. 
Total duration: 6 months in total for full data processing. 
Study 
Center(s) 
Single center – the study will take place at the Perelman Center For Advanced 
Medicine. 
Objectives 
Primary: 
To determine the effect of kinetic devices versus no device on pain of lidocaine 
injection as measured by 100mm visual analog scale. 
 
Secondary: 
To determine if the effect of kinetic devices on pain of local anesthetic injection is 
associated with anatomic location of the injection 
 
To determine patient preference of kinetic device versus no device for local anesthetic 
injection 
 
To gather qualitative data on changes to the patients experience of pain and overall 
experience using the kinetic anesthesia device versus no device 
Number of 
Subjects 
50 

2 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
Main 
Inclusion and 
Exclusion 
Criteria 
Key inclusion criteria 
1. Adult volunteers greater than or equal to 18 years of age  
2. Able and willing to provide informed consent 
3. Able to comprehend and comply with study instructions, and able to complete 
necessary evaluations. 
 
Key exclusion criteria 
1. Patients unable or unwilling to provide informed consent. 
2. Patients with lidocaine allergy  
3. Patients with known pain-related or neurological condition.  
4.Patients with a known cardiac condition  
5. Patients taking medications with a known Clinically Significant Drug Interaction with 
6. Vulnerable populations 
Investigation
al Product 
(drug, 
biologic, 
device, etc.) 
For Device 
include the 
planned use 
For Drug, 
food, 
cosmetic, etc. 
include the 
dose, route of 
administratio
n and dose 
regiment 
Blaine Labs Vibration Anesthesia Device. The device will be used as directed by the 
manufacturer, in the following manner: The device will be held by the person giving 
the injection in their off hand. It will be firmly pressed on the skin, 
turned on, adjacent to the injection 1-2 seconds before the injection is given. The 
injection will be given into the lighted target area of the kinetic anesthesia device. The 
device will be removed 1-2 seconds after the needle is withdrawn  
 
This device is on the US market legally.  This is a class 1 device, exempt from the 
need for approval or clearance.  Per the Code of Federal Regulations 
(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRsearch.cfm?FR=890.
5975-) this device may be used in clinical care or research.  
  
The device is being used in this research study in accordance with the FDA 
description 
Statistical 
Methodology 
Quantitative VAS data will be analyzed by a two-tailed t-test, and by linear regression 
model, incorporating location, and order of intervention (i.e. intervention first or 
second). Quantitative preferential data will be analyzed by logistic regression model 
incorporating location and order of intervention. 
Safety 
Evaluations  
Patients will be monitored for physical discomfort following lidocaine injection by 
experienced healthcare personnel. Any health-related events will be handled in 
accordance with standard of care clinical procedures. 
Data and 
Safety 
Monitoring 
Plan  
The Principal investigator will be responsible for monitoring the data quality and the 
ongoing safety of subjects.  
 
 
 

3 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
BACKGROUND AND STUDY RATIONALE 
 
This study will be conducted in full accordance all applicable University of Pennsylvania Research Policies 
and Procedures and all applicable Federal and state laws and regulations including [as applicable include 
the following regulations as they apply 45 CFR 46, 21 CFR Parts 50, 54, 56, 312, 314 and 812 and Good 
Clinical Practice: Consolidated Guidelines approved by the International Conference on Harmonisation 
(ICH). Note:Only include ICH compliance if the study will actually comply with these requirements.] All 
episodes of noncompliance will be documented. 
Introduction 
Lidocaine is used widely in the field of dermatology for anesthetizing the skin.  It is used commonly for 
minor procedures such as punch biopsies, and more complex outpatient facial reconstruction after skin 
cancer removal. Patients consistently experience discomfort from lidocaine injections, particularly since 
procedures on highly sensitive areas such as the nose and lips are common. Vibrating kinetic anesthesia 
devices have shown efficacy in reducing the pain of lidocaine injections in dentistry, pediatrics, and 
dermatology, however no studies exist investigating the effect of these devices on the pain of lidocaine 
injections on the face.  
 
The proposed study is a split-body randomized controlled trial of kinetic anesthesia devices on pain of 
lidocaine injection measured by a visual analog scale (VAS). Study participants will be healthy adult 
volunteers recruited from students, faculty, staff, and others healthy adult within the University of 
Pennsylvania. The study intervention will be application of the Blaine Labs Vibration Anesthesia Device at 
the time of injection, according to the manufacturer’s instructions. Participants will rate the pain from one 
injection with the kinetic anesthesia device (KAD) in use, and one injection without the KAD. Ratings will 
occur on a VAS. Participants will be asked whether they preferred the injection with or without the KAD. 
Injections will occur at these three sites: lateral forehead, nasofacial sulcus, and lateral back. Participants 
will be randomized to one of three locations, and to the order of intervention (i.e. first or second injection 
with KAD). Injections with and without the intervention will occur on the right and left side of the body 
respectively. 
1.1 
Background and Relevant Literature  
In many dermatologic procedures performed with local anesthetic, the injection of anesthetic is the 
most painful part of the procedure, and is thus one of the greatest barriers to complete comfort and 
enhanced patient satisfaction. Methods to minimize injection pain have been proposed and include slow 
rate of injection, with warmed, buffered lidocaine to decrease discomfort of local anesthetic injection 
(Kuboa), Vibrating devices have been shown to reduce the pain of local botulinum toxin injections, steroid 
injections for keloid treatment , local anesthetic injections in eyelid surgery , and in venipuncture in a 
pediatric emergency department. It is thought that vibration decreases the pain of injection by the gate 
control theory of pain, first proposed by Melzack and Wall, which asserts that the vibrating neural input 
overrides painful signals and prevents them from reaching the central nervous system. No study has yet 
investigated vibration devices for lidocaine injection at multiple body sites in the dermatologic surgery 
setting. The VAS is reported to be the most frequently used assessment instrument to evaluate the 
analgesic effects of various therapies and can detect minute pain changes. It has been systematically 
evaluated by Bijur et al, who determined that a change of 10mm or more on this scale represents a real 
clinical change in acute pain.  
 
Kuboa et al. Guidelines for the use of local anesthesia in office-based dermatologic surgery. JAAD. 
2016;74:6:1201-1219 Sharma P, et al. Investigating the efficacy of vibration anesthesia to reduce pain from 
cosmetic botulinum toxin injections. Aesthet Surg J. 
2011;31:966-971 Park KY, Kim BJ et al. Vibration Anesthesia for Pain Reduction During Intralesional 
Steroid Injection for Keloid Treatment. Derm Surg. 2017;43:724-727. Fayers, T et al. Vibration-assisted 
anesthesia in eyelid surgery. Othalmology. 2010;117:1453-1457 Baxter AL et al. An integration of 
vibration and cold relieves venipuncture pain in a pediatric emergency department. Pediatr Emerg Care. 

4 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
2011;27:1151-1156 KC Smith, JC Liu et al. Vibration anesthesia: A noninvasive method of reducing 
discomfort prior to dermatologic procedures. Dermatology Online Journal. 2004;10(2):1 Reed Michael 
D, van Nostran W. Assessing pain intensity with the visual analog scale: a plea for unity. J Clinic 
Pharm. 2014; 54:241-244. Bijur PE, Silver W, Gallagher EJ. Reliabil15. 
1.2 
Name and Description of the Investigational Product  
 
Blaine Labs Vibration Anesthesia Device. The device will be used as directed by the manufacturer, in the 
following manner: The device will be held by the person giving the injection in their non-dominant hand. 
The vibrating device will be firmly pressed on the skin, turned on, adjacent to the injection 1-2 seconds 
before the injection is given. The injection will be given into the lighted target area of the KAD. The device 
will be removed 1-2 seconds after the needle is withdrawn  
 
This device is on the US market legally.  This is a class 1 device, exempt from the need for approval or 
clearance.  Per the Code of Federal Regulations 
(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRsearch.cfm?FR=890.5975-) this device 
may be used in clinical care or research.  
  
The device is being used in this research study in accordance with the FDA description 
 
Further information regarding the device is attached in HS-ERA. 
1.2.1 
Clinical Data to Date 
Clinical data is summarized in the background section above. 
2 
Study Objectives 
Overall objectives 
The purpose of this study is to test the effect of KAD on the pain of lidocaine 
injection in healthy adult volunteers at sites with clinical relevance in dermatologic surgery. Primary 
Objectives: To determine the effect of KAD versus no device on pain of local anesthetic 
injection measured by VAS  
 Secondary Objectives: 1. To determine if the effect of KAD on pain of local anesthetic injection is 
associated with anatomic location of the injection;  2. To determine subject preference of KAD versus no 
device for local anesthetic injection; 3. To gather qualitative data on changes to the subjects’ experience of 
pain and overall experience using the KAD versus no device. 
 
2.1 
Primary Objective 
To determine the effect of KAD versus no device on pain of lidocaine injection, participants 
will be asked to evaluate each injection on a 100mm visual analog scale (VAS). Ratings will be 
quantified at intervals of 1mm from 1mm to 100mm, with 1 mm representing "no pain at all" and 100 
mm representing "worst pain imaginable." VAS ratings from injections with and without the device will be 
compared in each patient. 
2.2 
Secondary Objectives (if applicable) 
To determine if the effect of KAD on pain of local anesthetic injection is associated with 
anatomic location of the injection, VAS ratings will be used within a statistical model. To determine 
subject preference of kinetic device versus no device for local anesthetic injection, participants will be 
asked after the completion of their second injection: "Which method of injection did you prefer overall?" 
with the following answers: "With the vibrating kinetic anesthesia device being used" 
"without the vibrating kinetic anesthesia device" and "no preference" To gather qualitative data on 
changes to the subjects’ experience of pain and overall experience using KAD versus no device, patients 
will be asked the following questions: "Do you have any comments on how the KAD affected your 

5 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
injection experience?" "Were you bothered in any way by the KAD   [check yes or no] if so please 
comment". 
3 
Investigational Plan  
3.1 
General Design 
The study will be an open label split-body crossover trial, using healthy adult volunteers recruited from the 
faculty, staff and student body of the University of Pennsylvania, and from the University City area of 
Philadelphia. Participants will be randomized to one of three anatomic sites deemed relevant: the 
nasofacial sulcus, the lateral forehead, and the upper back. Participants will then be randomized to 
receive injection with the KAD first or second. The injection will be 0.5 cc of room temperature buffered 
lidocaine injected at constant slow speed (approximately 5 seconds) through a 30-gauge needle held 
perpendicular to the skin by the same surgeon, with verbal cues standardized. Injections will be given in 
accordance with the standard of practice. When the KAD is used it will be used as directed: firmly 
pressed on the skin adjacent to the injection, with the needle aimed into the lighted area. Volunteers will 
evaluate each injection immediately after it is complete using the visual analog scale. When both 
injections are completed, participants will indicate their preference of injection, complete qualitative 
questions, and note necessary demographic information. Injection location and order of intervention (i.e. 
first or second) will be noted. 
3.1.1 
Screening Phase 
Screening will take place at the time of the study. After informed consent and prior to the start of the 
investigative procedure, subjects will be verbally asked if they have preexisting cardiac conditions, 
neurological conditions, or previous adverse reactions to lidocaine. 
3.1.2 
Study Intervention Phase  
 1. The study will take place in an examination room in the Dermatologic Surgery clinic at the Perelman 
Center for Advanced Medicine.  
2. The KAD used will be the Blaine Labs Vibration Anesthesia Device. The device will be purchased from 
Blaine Labs directly.  
3. Injections will be made up of 0.5mL of room temperature 1% lidocaine buffered with 8.4% sodium 
bicarbonate, procured from the dermatologic surgery clinic. Injections will use the standard syringe with 30 
gauge needle.  
4. Before any procedure is done or information is collected for the study, subjects will be asked to read and 
sign the consent form. Adequate time will be given for subjects to review the Informed Consent Document 
and review any of their questions or concerns with the study staff or Principal Investigator. 
5. Baseline vital signs (heart rate and blood pressure) will be obtained prior to the first injection.  
6. Then each subject will be randomized to one location: nasofacial sulcus, lateral forehead or lateral back.  
7. Each subject will be randomized to receive the intervention with KAD either first or second.  
8. The first injection will always be on the left side and the second will always be on the right  
9. When the KAD is used for the injection, it will be held by the person giving the injection in their off hand. 
It will be firmly pressed on the skin, turned on, adjacent to the injection 1-2 seconds before the injection is 
given. The injection will be given into the lighted target area of the KAD. The device will be removed 1-2 
seconds after the needle is withdrawn.  
10. Each injection will be given in accordance with the current standard of practice.  Injections will be given 
using the formulation and needle noted above. Injections will be given with the needle held perpendicular 
to the skin. The speed of the injection will be slow, aiming for 5 seconds to empty the syringe. All injections 
will be performed by Dr. Sobanko, with verbal cues standardized.  
11. After each injection, study participants will be asked to document their level of acute pain using the 
VAS. A paper and pen version of the scale will be used. 
12. After both injections are complete, safety vitals will again be obtained (heart rate, blood pressure) in 
order to assess whether subject has tolerated the injection without any adverse reactions. If necessary, 
repeat vitals will be obtained until the Principal Investigator feels the subject is medically clear to leave. 

6 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
13. After both injections are complete the study participant will be asked to fill out the short questionnaire 
about preference of injection, qualitative comments, age, and sex.  
14. The location and order of the injections will be noted by study personnel. The VAS scales will be 
measured.  
15. At this point, data collection will be complete. Unless an adverse event was noted, or subject has 
additional questions or concerns regarding their participation or study-related procedures,  participants will 
be compensated and will be free to go at this point.  
16. The kinetic anesthesia device will be cleaned with an alcohol swab. Study personnel will wash hands 
and repeat the exercise on the next participant. 
3.1.3 
Allocation to Interventional Group  
Participants will be randomized to one of three locations: nasofacial sulcus, lateral forehead, or upper back. 
Additionally, subjects will be randomized to receive the intervention with vibration anesthesia device on 
their first (left) or second (right)-sided injection. This is a split body study so each participant will receive 2 
total injections – one with and one without the intervention. Randomization will be achieved by the selection 
of a sealed envelope by each study participant, that will have a location and an order listed. This will 
randomize subjects and will ensure that groups can be balanced, by creating equal numbers of envelopes 
for each of the groups. 
3.2 
 Study Endpoints  
3.2.1 
Primary Study Endpoints 
Each injection will be evaluated by 100mm visual analog scale (VAS) for acute pain immediately after 
the injection is complete. Patients visually indicate by drawing on paper where their pain is on a 10 cm 
line, with one end labelled no pain at all and the other worst pain imaginable. The primary endpoint is a 
statistically significant mean reduction in acute pain on VAS of 10mm or more, per Bijur et al, who 
determined that this change indicates a real clinical change in acute pain. 
 
3.2.2 
Secondary Study Endpoints 
Following the completion of both injections, volunteers will indicate which injection they preferred, with a 
no preference option included. Patients will also be queried on demographic information after the 
injections have been completed. They will be asked age, sex, and role at the University of Pennsylvania. 
Because pain is characterized as quantitative AND qualitative, there will be a free response section for 
comments, specifically asking “Do you have any comments on how the kinetic anesthesia device affected 
your injection experience?” A second qualitative entry section will ask: “Were you bothered in any way by 
the KAD [check yes or no] if so please comment” 
4 
Study Population and Duration of Participation  
4.1 
Inclusion / Exclusion Criteria 
Inclusion / Exclusion Criteria will be verified by the Principal Investigator.  
 
4.2 Key inclusion criteria 
1. Adult volunteers greater than or equal to 18 years of age  
2. Able and willing to provide informed consent 
3. Able to comprehend and comply with study instructions, and able to complete necessary evaluations. 
4.3 Exclusion Criteria 
1. Patients unable or unwilling to provide informed consent. 
2. Patients with lidocaine allergy  
3. Patients with known pain-related or neurological condition.  
4.Patients with a known cardiac condition  

7 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
5. Patients taking medications with a known Clinically Significant Drug Interaction with lidocaine. 
6. Patients who are pregnant or Nursing mothers.  
7. Vulnerable populations  
 
4.4 Subject Recruitment  
Subject recruitment will occur by email to the Perelman School of Medicine student body. Email text is 
attached. Further recruitment will occur from flyers posted around the University of Pennsylvania 
campus and University City area. Flyer attached. Study recruitment information will be circulated via the 
UPHS broadcast email. Materials attached. The study will be posted on the iConnect tool. 
 
4.5 
Duration of Study Participation 
Recruitment and enrollment period: 2 months  
Subjects' length of participation in the study: 1 day.  
The entire encounter should take less than one hour.  
Project date of the proposed study: Recruitment and enrollment will commence with IRB approval.  
A total time of 6 months is requested for data analysis. 
4.6 
Total Number of Subjects and Sites  
50 subjects enrolled for the study taking place at one site – Perelman Center for Advanced Medicine. 
4.7 
Vulnerable Populations:  
Vulnerable populations will not be included in this study  
5 
Study Intervention (Study drug, device, biologic, vaccine, food etc.) 
5.1 
Description 
Blaine Labs Vibration Anesthesia Device. The device will be used as directed by the manufacturer, in the 
following manner: The device will be held by the person giving the injection in their off hand. It will be 
firmly pressed on the skin, turned on, adjacent to the injection 1-2 seconds before the injection is given. 
The injection will be given into the lighted target area of the kinetic anesthesia device. The device will be 
removed 1-2 seconds after the needle is withdrawn.  
 
This device is on the US market legally.  This is a class 1 device, exempt from the need for approval or 
clearance.  Per the Code of Federal Regulations 
(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRsearch.cfm?FR=890.5975-) this device 
may be used in clinical care or research.  
  
The device is being used in this research study in accordance with the FDA description 
 
Further information regarding the device is attached in HS-ERA. 
 
5.2 
Receipt  
The device will be purchased directly from Blaine Labs and shipped to Dr. Joseph Sobanko in the Perelman 
Center for Advanced Medicine.  
 
6 
Study Procedures 
 

8 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
6.1 
Study Intervention Phase 
1. The study will take place in an examination room in the Dermatologic Surgery clinic at the Perelman 
Center for Advanced Medicine.  
2. The KAD used will be the Blaine Labs Vibration Anesthesia Device. The device will be purchased from 
Blaine Labs directly.  
3. Injections will be made up of 0.5mL of room temperature 1% lidocaine buffered with 8.4% sodium 
bicarbonate, procured from the dermatologic surgery clinic. Injections will use the standard syringe with 30-
gauge needle.  
4. Before any procedure is done or information is collected for the study, subjects will be asked to read and 
sign the consent form. Adequate time will be given for subjects to review the Informed Consent Document 
and review any of their questions or concerns with the study staff or Principal Investigator. 
5. Baseline vital signs (heart rate, blood pressure,) will be obtained prior to the first injection. The 
participant’s baseline respiratory rate and adequacy of ventilation will also be noted. We will additionally 
specify that the study procedure will take place in a setting where resuscitative equipment and personnel 
for treating adverse reactions will be immediately available.” 
6. Then each subject will be randomized to one location: nasofacial sulcus, lateral forehead or lateral back.  
7. Each subject will be randomized to receive the intervention with KAD either first or second.  
8. The first injection will always be on the left side and the second will always be on the right  
9. When the KAD is used for the injection, it will be held by the person giving the injection in their off hand. 
It will be firmly pressed on the skin, turned on, adjacent to the injection 1-2 seconds before the injection is 
given. The injection will be given into the lighted target area of the KAD. The device will be removed 1-2 
seconds after the needle is withdrawn.  
10. Each injection will be given in accordance with the current standard of practice.  Injections will be given 
using the formulation and needle noted above. Injections will be given with the needle held perpendicular 
to the skin. The speed of the injection will be slow, aiming for 5 seconds to empty the syringe. All injections 
will be performed by Dr. Sobanko, with verbal cues standardized.  
11. After each injection, study participants will be asked to document their level of acute pain using the 
VAS. A paper and pen version of the scale will be used. 
12. After both injections are complete, safety vitals will again be obtained (heart rate, blood pressure, 
respiratory rate and adequacy of ventilation) in order to assess whether subject has tolerated the injection 
without any adverse reactions. If necessary, repeat vitals will be obtained until the Principal Investigator 
feels the subject is medically clear to leave. 
13. After both injections are complete the study participant will be asked to fill out the short questionnaire 
about preference of injection, qualitative comments, age, and sex.  
14. The location and order of the injections will be noted by study personnel. The VAS scales will be 
measured.  
15. At this point, data collection will be complete. Unless an adverse event was noted, or subject has 
additional questions or concerns regarding their participation or study-related procedures, participants will 
be compensated and will be free to go at this point.  
16. The kinetic anesthesia device will be cleaned with an alcohol swab. Study personnel will wash hands 
and repeat the exercise on the next participant. 
. 
6.2 
Subject Withdrawal  
Subjects may withdraw at any time by indicating this to investigators. 
7 
Study Evaluations and Measurements  
Each injection will be evaluated by 100mm visual analog scale (VAS) for acute pain immediately after 
the injection is complete. Patients visually indicate by drawing on paper where their pain is on a 10 cm 
line, with one end labelled no pain at all and the other worst pain imaginable. The primary endpoint is a 
statistically significant mean reduction in acute pain on VAS of 10mm or more, per Bijur et al, who 
determined that this change indicates a real clinical change in acute pain. Following the completion of 
both injections, volunteers will indicate which injection they preferred, with a no preference option 
included. Patients will also be queried on demographic information after the injections have been 

9 
 
 
CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
completed. They will be asked age, sex, role at University of Pennsylvania. Because pain is 
characterized as quantitative AND qualitative, include a free response section for comments, 
specifically asking Do you have any comments on how the kinetic anesthesia device affected your 
injection experience? A second qualitative entry section will ask: Were you bothered in any way by the 
VAD [check yes or no] if so please comment  
 
7.1 
Vital Signs 
Vital signs will be collected by the study staff overseeing the visit. Baseline vitals will be established prior 
to the first injection and recorded on the data source sheet. Post-Injection Vitals will be obtained following 
the second injection, before subjects begin to fill out their final survey sheet. If necessary, repeat vitals will 
be obtained until the Principal Investigator feels that the subject is medically cleared to leave.  
8 
Statistical Plan 
8.1 
Primary Endpoint 
Each injection will be evaluated by 100mm visual analog scale (VAS) for acute pain immediately after 
the injection is complete. Patients visually indicate by drawing on paper where their pain is on a 10 cm 
line, with one end labeled no pain at all and the other worst pain imaginable. The primary endpoint is a 
statistically significant mean reduction in acute pain on VAS of 10mm or more, per Bijur et al, who 
determined that this change indicates a real clinical change in acute pain. Quantitative VAS data will be 
analyzed by a two-tailed t-test, and by linear regression model, incorporating location, and order of 
intervention (i.e. intervention 
first or second). 
 
8.2 
Secondary Endpoints  
Following the completion of both injections, volunteers will indicate which injection they preferred, with a 
no preference option included. Patients will also be queried on demographic information after the 
injections have been completed. They will be asked age, sex, role at University of Pennsylvania. Because 
pain is characterized as quantitative AND qualitative, include a free response section for comments, 
specifically asking Do you have any comments on how the kinetic anesthesia device affected your 
injection experience? A second qualitative entry section will ask: Were you bothered in any way by the 
VAD [check yes or no] if so please comment. Quantitative VAS data will be analyzed by a two-tailed ttest, 
and by linear regression model, incorporating location, and order of intervention (i.e. intervention 
first or second). Quantitative preferential data will be analyzed by logistic regression model 
incorporating location and order of intervention. 
8.3 
Sample Size and Power Determination 
Sample size was calculated in STATA using the change in VAS needed for clinical significance, in 
concordance with effect sizes and standard deviations from previous studies. Sample size calculated to 
detect a clinically significant difference at each of three locations with alpha = 0.05 and a power of 0.8. 
8.4 
Statistical Methods 
Quantitative VAS data will be analyzed by a two-tailed t-test, and by linear regression model, 
incorporating location, and order of intervention (i.e. intervention first or second). Quantitative preferential 
data will be analyzed by logistic regression model incorporating location and order of intervention. 
  

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9 
Safety and Adverse Events 
9.1 
Definitions 
9.1.1 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
 
For FDA regulated studies the FDA defines an adverse event as the following:  
 
Adverse event means any untoward medical occurrence associated with the use of a drug in humans 
whether or not considered drug related.  
 
In this study, the most likely event would be an adverse reaction to lidocaine. In this specific setting, using 
this dosage of lidocaine the most likely reaction will occur at the local injection site. A systemic reaction 
would be exceedingly unlikely.  
9.1.2 
Serious Adverse Event 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance.   They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above.  For example, drug overdose or abuse, a seizure that did not result 
in in-patient hospitalization, or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
 
For additional information on definitions and clarifications which may be helpful in creating the safety 
monitoring portion refer to Appendix 17.7 
 
9.2 
Recording of Adverse Events 
At each contact with the subject, the investigator will seek information on adverse events by specific 
questioning and, as appropriate, by examination.  Information on all adverse events will be recorded 
immediately in the source document, and also in the appropriate adverse event module of the case report 
form (CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures results should be 
recorded in the source document, though should be grouped under one diagnosis. 
 

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CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
All adverse events occurring during the study period will be recorded.  The clinical course of each event will 
be followed until resolution, stabilization, or until it has been determined that the study intervention or 
participation is not the cause.  Serious adverse events that are still ongoing at the end of the study period 
will be followed up to determine the final outcome.  Any serious adverse event that occurs after the study 
period and is considered to be possibly related to the study intervention or study participation will be 
recorded and reported immediately. 
9.3 
Relationship of AE to Study  
9.4 
Reporting of Adverse Events, Adverse Device Effects and Unanticipated Problems 
Investigators and the protocol sponsor (which may or may not be a Penn Investigator) must conform to the 
adverse event reporting timelines, formats and requirements of the various entities to which they are 
responsible,  
 
If the report is supplied as a narrative, the minimum necessary information to be provided at the time of the 
initial report includes: 
• 
Study identifier 
• 
Study Center 
• 
Subject number 
• 
A description of the event 
• 
Date of onset 
• 
Current status 
• 
Whether study intervention was discontinued 
• 
The reason why the event is classified as serious 
• 
Investigator assessment of the association 
between the event and study intervention 
 
 
Additionally all other events (unanticipated problems, adverse reactions, unanticipated adverse device 
effects and subject complaints  will be recorded and reported with respect to institutional and federal policies 
as described in the Penn Manual and below.  
9.4.1 
Follow-up report 
If an SAE has not resolved at the time of the initial report and new information arises that changes the 
investigator’s assessment of the event, a follow-up report including all relevant new or reassessed 
information (e.g., concomitant medication, medical history) should be submitted to the IRB. The investigator 
is responsible for ensuring that all SAE are followed until either resolved or stable.  
9.4.2 
Data and Safety Monitoring Plan 
Data and safety monitoring will be performed by the principal investigator. Monitoring will be conducted per 
the Lidocaine drug label: “Careful and constant monitoring of cardiovascular and respiratory (adequacy of 
ventilation) vital signs and the patients state of consciousness should be accomplished after each local 
anesthetic injection.” For additional safety precautions, vitals will be also be obtained prior to subject 
receiving their first injection. Vitals will include heart rate, blood pressure, respiratory rate. Assessment of 
the participants adequacy of ventilation will also be carried out prior to and after the lidocaine injections.  
 
10 Study Administration, Data Handling and Record Keeping 
10.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a signed 
subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  

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CONFIDENTIAL 
 
This material is the property of the University of Pennsylvania.   
 
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains 
the ability to use all information collected prior to the revocation of subject authorization.  For subjects that 
have revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect 
at least vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
10.2 Data Collection and Management  
Paper-based records will be kept in a secure location and only be accessible to personnel involved in the 
study. Paper based records will be input into a secure electronic database and the paper records will be 
destroyed as soon as is possible.  
 
Computer-based files will only be made available to personnel involved in the study through the use of 
access privileges and passwords, and will be kept on password-secured computers. 
 
Wherever feasible, identifiers will be removed from study-related information, with subjects assigned unique 
non-identifiable study IDs.  
 
Each subject will be assigned a random study ID number, and a key will be used to link this number to their 
identifiable information. This link will be used only to track adverse events if they occur. 
Study data, i.e. visual analog scale ratings, preferences, and demographic information will not be connected 
with names, birth dates, or MRNs at any time. Data will be collected in this manner on paper and will be 
immediately encoded in a secure computer database, and the paper records will be kept securely until after 
the closure of the study with the IRB.  
Electronic identifiable information will be stored on the Penn Medicine server and that any paper documents 
with identifiers (such as consent forms) will be stored in a secure location under lock and key. 
Data will be kept on password-protected computers. 
A resource at the University of Pennsylvania that can assist you in developing and maintaining data 
collection and management systems is the Clinical Research Computing Unit (CRCU) in the Center for 
Clinical Epidemiology and Biostatistics (CCEB) Records Retention 
11 Ethical Considerations 
11.1 Risks 
The main risk of this study is the (expected) discomfort of lidocaine injection in the face and back. 
Lidocaine is a well-studied and well-tolerated drug. The risks of injecting this dose of lidocaine 
(0.5mL, 1%) are exceedingly low. The most likely reaction to this dose will be at the site of the injection.  
Inadvertent intravenous injection is theoretically possible but has not happened in over hundreds of 
thousands of injections in our clinic while properly anesthetizing skin for cancer removal since 2005.  
Furthermore, the concentrations and volume injected has an infinitesimal risk of inducing systemic side 
effects. Adverse reactions to lidocaine will be treated according to standard of care. Study personnel are 
also well trained in diagnosing side effects of lidocaine toxicity. There will be no epinephrine used in this 
study (a common additive to lidocaine) - this lowers the chances of an adverse reaction. There are no 
known risks from application of a KAD at the peri-injection site. Covino BG: Pharmacology of local 
anesthetic agents. Br J Anaesth. 58:701-716 1986 Walsh A, Walsh S: Local anesthesia and the 
dermatologist. Clin Exp Dermatol. 36(4):337-343 2011.  

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This material is the property of the University of Pennsylvania.   
 
11.2 Benefits 
Anecdotal evidence claims that local anesthetic injection is the most painful part of minor dermatological 
procedures. A reduction in the pain of injections by the vibration device would improve the overall patient 
experience and would be easily generalizable to all patients in the clinic, and possibly patients in 
outpatient surgical settings. Furthermore, if successful this study would provide evidence based 
guidelines for the proper use of these medical devices in multiple locations on the body. 
11.3 Risk Benefit Assessment 
We anticipate that the potential benefits and knowledge to be gained by this study outweigh the 
potential risks to subjects involved in this research study for the following reasons: Individuals have 
volunteered to participate and given informed consent to enter the study. They face minimal risk. There are 
no direct benefits for participation in the study. The knowledge gained will benefit those receiving similar 
injections in the future. 
11.4 Informed Consent Process / HIPAA Authorization  
Informed consent will be obtained in writing at the time of the investigative procedure, by the PI and 
research assistant. Prospective participants, after responding to a recruitment email, will receive a full 
description of the study procedure, risks and benefits. They will then be able to decide whether they 
wish to participate in the study. If they choose to participate, subjects will be informed again on the day 
of the study, and written consent will be obtained at that time. The language used will be targeted for a 
layman's understanding. This should be well-understood by the target subject population of medical 
students. It is not anticipated that subjects incapable of consent or those requiring legally authorized 
representatives will enroll in the study. Participants will be allowed to withdraw from the study at any 
time by a verbal refusal to proceed.  
 
11.5 Conflict of Interest 
No conflicts of interest to report 
11.6 Subject Stipends or Payments 
For their time and effort of being in a trial, subjects will be compensated $25.00 on a Greenphire Clincard 
at the end of their completed visit.  
 
12 References 
1. Baxter AL et al. An integration of vibration and cold relieves venipuncture pain in a pediatric 
emergency department. Pediatr Emerg Care. 2011;27:1151-1156 
2. Bijur PE, Silver W, Gallagher EJ. Reliability of the visual analog scale for measurement of 
acute pain. Acad Emerg. Med. 2001;8:1153-1157. 
3. Covino BG: Pharmacology of local anesthetic agents. Br J Anaesth. 58:701-716 1986 
4. Fayers, T et al. Vibration-assisted anesthesia in eyelid surgery. Othalmology. 2010;117:1453-1457 
5. Kuboa et al. Guidelines for the use of local anesthesia in office-based dermatologic surgery. JAAD. 
2016;74:6:1201-1219 
6. Park KY, Kim BJ et al. Vibration Anesthesia for Pain Reduction During Intralesional Steroid Injection 
for Keloid Treatment. Derm Surg. 2017;43:724-727 
7. Reed Michael D, van Nostran W. Assessing pain intensity with the visual analog scale: a plea for 
unity. J Clinic Pharm. 2014; 54:241-244 
8. Walsh A, Walsh S: Local anesthesia and the dermatologist. Clin Exp Dermatol. 36(4):337-343 2011 
13 Attachments 
The following documents are attached: 
• Sample Consent Form 

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This material is the property of the University of Pennsylvania.   
 
• Cover Letter 
• Sample recruitment flyer 
• Sample recruitment letter 
• Additional device information 
• Sample electronic recruiting communication 
• Sample of data collection sheet 
• Brochures for buffered and un-buffered lidocaine, Sodium Bicarbonate 
• Sample of Inclusion/Exclusion criteria data sheet 
• Official manufacturers device instructions. 
13.1