Prospective, Crossover, Open Label Study to Evaluate the Effects of Vibration Anesthesia With DigiVibe on Pain in Subjects Undergoing Intramuscular Injections, Subcutaneous Injections, and Fingersticks (VIB-DIGI)
Phase: NA
Conditions: Healthy
Sponsor: East Coast Institute for Research

 
 
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Prospective, Crossover, Open Label Study to Evaluate the Effects of Vibration 
Anesthesia with DigiVibe on Pain in Subjects Undergoing Intramuscular Injections, 
Subcutaneous Injections, and Fingersticks (VIB-DIGI) 
 
 
 
Short Title: Effects of DigiVibe on Pain in Subjects Undergoing Intramuscular Injections, 
Subcutaneous Injections, and Fingersticks (VIB-DIGI) 
 
Protocol Date: May 4, 2025 
 
Version #: 1.0 
 
 
 

 
 
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ABBREVIATIONS USED IN THE PROTOCOL 
 
Abbreviation 
Term 
AE 
Adverse Event 
SAE 
Serious Adverse Event 
GCP 
IRB 
Good Clinical Practice 
Institutional Review Board 
ICF 
Informed Consent Form 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
EOS 
End of Study 
FDA 
Food and Drug Administration 
US 
United States 
EMR 
Electronic Medical Record 
SOA 
SAS 
Schedule of Activities 
Statistical Analysis System 
IM 
Intramuscular 
SC 
Subcutaneous  
TENS 
Transcutaneous Electrical Nerve Stimulation 
LB 
Long Buccal 
IAN 
Inferior Alveolar Nerve 
FAS 
Facial Anxiety Scales 
VAS 
Visual Analog Scale 
SSI 
Symptom Severity Index 
H0 
Null Hypothesis 
HA 
Alternative Hypothesis 
n= 
Number  
NS 
Normal Saline 
BMI 
Body Mass Index 
NSAIDs 
Nonsteroidal Anti-Inflammatory Drugs 
BP 
Blood Pressure  
 
 

 
 
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Table of Contents 
 
ABBREVIATIONS USED IN THE PROTOCOL ............................................................................. 2 
1 
INTRODUCTION ..................................................................................................................... 5 
1.1 
Background and Significance ....................................................................................... 5 
1.2 
Risk Assessment ........................................................................................................... 7 
2 
ETHICS .................................................................................................................................... 7 
2.1 
Good Clinical Practice (GCP) ........................................................................................ 7 
2.2 
Institutional Review Board (IRB) .................................................................................. 8 
2.3 
Informed Consent ........................................................................................................ 8 
3 
HYPOTHESIS ........................................................................................................................... 9 
4 
STUDY DESIGN ....................................................................................................................... 9 
4.1 
Description ................................................................................................................... 9 
4.2 
Study Objectives / Endpoints ..................................................................................... 10 
4.3 
Study Population ........................................................................................................ 10 
4.3.1 
Study Subjects and Approximate Number of Subjects ............................... 10 
4.3.2 
Eligibility Criteria ......................................................................................... 10 
4.4 
Study Duration ........................................................................................................... 11 
4.4.1 
Approximate Duration of Subject Participation .......................................... 11 
4.4.2 
Screen Failures ............................................................................................. 11 
4.4.3 
Premature Study Treatment Discontinuation ............................................. 11 
4.4.4 
Withdrawal documentation ........................................................................ 12 
4.4.5 
Follow-up on Withdrawn Subjects .............................................................. 12 
4.4.6 
Approximate Duration of Study ................................................................... 12 

 
 
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4.5 
Study Visits ................................................................................................................. 12 
4.6 
Study Procedures ....................................................................................................... 14 
4.7 
Study Treatments ....................................................................................................... 17 
4.7.1 
Investigational Medical Products ................................................................ 17 
4.8 
Study Schedule of Activities (SOA)............................................................................. 17 
4.9 
Data Analysis .............................................................................................................. 18 
4.9.1 
Statistical Analysis Plan ................................................................................ 18 
4.9.2 
Statistical Power and Sample Size Considerations ...................................... 18 
4.10 Data Management ..................................................................................................... 18 
4.10.1 
Data Collection and Storage ........................................................................ 18 
4.10.2 
Records Retention ....................................................................................... 19 
5 
SAFETY MONITORING .......................................................................................................... 19 
5.1 
Adverse Event Reporting............................................................................................ 19 
5.2 
Definitions .................................................................................................................. 20 
5.3 
Recording and Reporting ........................................................................................... 22 
6 
ADMINISTRATIVE PROCEDURES .......................................................................................... 22 
6.1.1 
Changes to the Protocol .............................................................................. 22 
6.1.2 
Adherence to the Protocol .......................................................................... 22 
6.1.3 
Monitoring Procedures ............................................................................... 23 
7 
PUBLICATION PLAN .............................................................................................................. 23 
8 
REFERENCES ........................................................................................................................ 24 
 

 
 
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1 
INTRODUCTION 
1.1 
Background and Significance 
Each year in the United States, millions of individuals undergo medical procedures 
involving needles, including intramuscular (IM) injections, subcutaneous (SC) injections, 
and fingersticks for blood glucose monitoring and other point of care testing. These 
procedures are essential for administering vaccines, managing chronic conditions, and 
monitoring health. However, a significant portion of the population experience a fear of 
needles due to the associated pain, which can impact their willingness to undergo these 
necessary medical interventions. This fear can result in missed vaccinations, poor 
adherence to medication regimens, and inadequate monitoring of conditions, such as 
diabetes. Understanding the prevalence and impact of needle fear due to pain is crucial 
for developing strategies to improve patient compliance and overall health outcomes. 
Pain is transmitted through nociceptors, derived from neural crest cells in the spinal cord 
during gestation and relayed by the thalamus. While the full mechanism of pain is 
unclear, the ‘Gate Control Theory of Pain’, introduced by Melzack and Wall in the 1960s, 
in widely used. This Theory suggests that open spinal gates allow for painful stimuli to 
permeate through the body while closed gates halt that process 1. This theory also 
highlights two types of afferent fibers that mediate the pain stimuli – fast-transmitting 
myelinated A fibers (pricking pain) and slow-transmitting unmyelinated C fibers (burning 
pain) 1.  
 
Pain associated with needle-based procedures can be reduced through a variety of non-
interventional methods, including distraction techniques, cooling, and tactile 
stimulation. One such method gaining attention is vibration therapy (also known as 
vibration anesthesia), which uses localized mechanical stimulation to interfere with pain 
signal transmission and reduce perceived discomfort. Vibrations serve as a competing 
sensory input that can help block pain signals from reaching the brain, consistent with 
the gate control theory of pain (eg. closed gate process). Over the years, vibration 
devices such as the Transcutaneous Electrical Nerve Stimulation (TENS) Unit machine 
(1974), Buzzy (2009), and Vibracool (2015), have demonstrated that non-painful stimuli 
effectively be used to reduce the perception of pain.   
 
DigiVibe is a cordless, handheld device designed to reduce the pain caused by needles 
that is a U.S. Food and Drug Administration (FDA) registered device to be used to reduce 

 
 
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the pain associated with fingerstick blood glucose testing. By applying targeted 
vibrations to the skin prior to a needle stick, it interferes with pain signal transmission to 
the brain, making the process more comfortable for users.  
A prospective, randomized study comparing vapocoolant (cold) spray versus vibration 
anesthesia evaluated pre-injection (expected pain) and a post-injection pain (actual 
perceived pain). One-hundred and eighty (180) subjects with arthritis, tendinopathy, or 
compression neuropathy of the hand, wrist, or elbow were randomized to one of three 
groups – no anesthesia (n=60), injection with vapocoolant spray (n=60), and injection 
with vibratory anesthesia (n=60). Subjects were provided a 10-point Likert scale pre-
injection, to assess expected pain, and a post-injection, to assess actual perceived pain.  
Pre-injection pain scores for no anesthesia, vapocoolant, and vibration were 5.57, 5.32 
(p-value 0.01470), and 5.73 (p-value 0.0446), respectively. Post-injection pain scores 
were the following for no anesthesia 5.18 (CI: -1.22 to 0.45), cold spray 4.12 (p-value: 
0.1470; CI: -1.95 to 0.45), and vibration anesthesia 4.18 (p value 0.0446; CI: -2.34 to 
0.76). These results suggest that vibration anesthesia could be a useful adjunct for 
injections of the hand, wrist, or elbow – which has been consistent with previously 
published data 3. 
 
The Vibration Device to Control Injection Discomfort trial analyzed the discomfort level 
of 60 subjects (30 men and 30 women) who needed local anesthesia for intraoral long 
buccal (LB) and inferior alveolar nerve (IAN) injections. This study evaluated pain and 
anxiety levels during anesthesia administration with the DentalVibe® Injection Comfort 
System, which uses pulsation to reduce discomfort during injection administration. 
Anxiety prior to an injection was measured using the facial anxiety scales (FAS), acute 
pain intensity during injection was assessed with the Visual Analog Scale (VAS), and 
symptom history over the past six months was recorded using the Symptom Severity 
Index (SSI) 4. The study did not showcase statistically significant differences in any 
measures. However, individuals who did not receive DentalVibe® had higher scores 
across all measures for both injections indicating that there was a clinically meaningful 
reduction in pain with the use of DentalVibe® in combination with injections during 
dental anesthesia4.  

 
 
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1.2 
Risk Assessment 
DigiVibe 
The DigiVibe device is considered to be safe and noninvasive and the potential 
risks to subjects in this study are minimal, if any.  
 
 
 
Skin Irritation or Discomfort 
Prolonged or overly intense use of DigiVibe in one area of the skin could cause 
temporary redness, bruising, or minor soreness, specifically in patients with 
sensitive skin.  
 
Normal Saline and Injections 
Normal saline will be used for intramuscular and subcutaneous injections and, 
while it is an inert and widely used solution, intramuscular and subcutaneous 
injections may have some potential risks, if any.  
 
As with any standard of care injections, subjects may experience soreness, pain, 
redness, swelling, or tenderness at the injection site. Mild bruising or local 
irritation may also occur with a potential for minor bleeding at the injection site. 
Though rare, there is a small risk of skin or soft tissue infection at the injection 
site.  
 
2 ETHICS 
 
2.1 
Good Clinical Practice (GCP) 
 
This study will be conducted in accordance with Good Clinical Practice (GCP), in 
accordance with the United States Code of Federal Regulations, Title 21, Part 50 
(21CFR50). The study will be conducted in compliance with the protocol.  
All potential protocol deviations or violations must be reported to the IRB immediately. 
A protocol deviation or violation is defined as a violation of the GCP guidelines regarding 
the study protocol, which is likely to significantly affect the safety of the subjects in the 

 
 
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study or the scientific validity of the study. Study staff involved in conducting this study 
will be qualified by education, training, and experience to perform their respective tasks 
and this study will not use study staff where there has been scientific misconduct or 
fraud (e.g., loss of medical licensure, debarment). 
2.2 
Institutional Review Board (IRB) 
 
Before initiation of the study, the investigator must have received IRB approval for the 
protocol, Informed Consent Form (ICF), subject recruitment materials (e.g., 
advertisements), and any other written information to be provided to subjects.   
During the clinical study, any amendment to the clinical trial protocol must be submitted 
to the IRB before implementation, unless the change is necessary to eliminate an 
immediate hazard to the subjects, in which case the IRB should be promptly informed. 
The IRB should also be informed of any event likely to impact the safety of subjects in 
the clinical trial. The investigator must send a progress report to the IRB at least 
annually, as well as a summary of the clinical trial’s outcomes at the end of the clinical 
trial. 
2.3 
Informed Consent 
The investigator will ensure that the ICF includes all elements required by GCP and 
applicable regulatory requirements, as well as follow the ethical principles within the 
Declaration of Helsinki. The investigator will ensure that the ICF is reviewed and 
approved by the IRB prior to use in a clinical trial.  
The Investigator, or a person designated by the Investigator, should fully inform the 
subject of all pertinent aspects of the clinical trial including the purpose, potential risks, 
required procedures, etc. in which they volunteer to participate. All subjects should be 
informed about the study in a language and at a level they are able to understand. In 
circumstances where consent cannot be given to subjects, their legally acceptable 
representatives must be clearly and fully informed about the purpose, potential risks, 
required procedures, etc. regarding the clinical trial in which the subject will participate. 

 
 
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Prior to a subject’s participation in the clinical trial, the written ICF should be signed and 
dated personally (by the subject) or by the subject’s legally acceptable representative 
and by the person who conducted the informed consent discussion. A copy of the signed 
and dated written ICF will be provided to the subject. 
 
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HYPOTHESIS  
 
Null Hypothesis (H0): DigiVibe vibration anesthesia has no clinically significant impact on pain 
scores. 
Alternative Hypothesis (HA): DigiVibe vibration anesthesia has a clinically significant impact on 
pain scores. 
 
4 
STUDY DESIGN 
 
4.1 
Description 
This is a single-center, unblinded, prospective, cross-over study. The study population will 
include twenty (n=20) healthy subjects (10 men and 10 women) over the age of 18 with a 
self-reported fear/dislike of needles. Subjects who qualify for the study based on the 
study inclusion and exclusion criteria and who consent to participate in the study will 
undergo two (2) intramuscular (IM) injections in the deltoid muscle, two (2) 
subcutaneous (SC) injections in the abdomen, and two (2) fingersticks with a lancing 
device in the middle finger. Normal Saline (NS) will be used for the IM and SC injections. 
The study duration per subject is expected to be one (1) day.  
 
While the complete mechanisms of pain and pain diversion are not completely 
understood, DigiVibe locally targets the skin’s pain receptors. Therefore, it is proposed 
that the vibrations from the DigiVibe device will counteract and/or lessen the pain 
around the injection site. This study will determine whether the use of DigiVibe during a 
procedure requiring injections provides greater reduction in pain than injections with no 
intervention (standard of care). This information will aid healthcare providers in selecting 
the best approach to management of pain in patients who must undergo injections that 
could cause pain and may benefit from additional pain reduction. 

 
 
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4.2 
Study Objectives / Endpoints   
Objective 
Endpoint 
Primary 
To demonstrate if the use of DigiVibe is 
superior to no intervention in reducing pain 
scores during intramuscular injections, 
subcutaneous injections, and fingersticks. 
Difference between DigiVibe and no 
intervention on pain scores. 
 
4.3 
Study Population 
 
4.3.1 Study Subjects and Approximate Number of Subjects 
 
This is a single-center study which will include the participation of twenty (20) subjects.  
 
4.3.2 Eligibility Criteria 
Inclusion Criteria: 
Subjects must meet each of the following inclusion criteria to be eligible for enrollment 
into the study: 
1. Age ≥ 18 years  
2. BMI 18.5-29.9 kg/m2 (normal) 
3. Self-reported fear/dislike of needles 
Exclusion Criteria: 
Subjects presenting with any of the following exclusion criteria will not be eligible for 
enrollment into the study: 
1. Chronic (daily) use of nonsteroidal anti-inflammatory drugs (NSAIDs) (i.e. 
ibuprofen, aspirin, naproxen, etc.), antiplatelet medications (i.e. clopidogrel, 
prasugrel, ticagrelor, cangrelor, cilostazol, etc), or anticoagulant medications (i.e. 
warfarin, dabigatran, rivaroxaban, apixaban, edoxaban, heparin, enoxaparin, 
fondaparinux, etc.) 

 
 
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o Note: NSAIDs used as needed are not excluded as long as they are not 
used within 3 days of study screening and enrollment  
2. Chronic (daily) use of analgesics (i.e. acetaminophen, NSAIDs [ie. ibuprofen, 
naproxen], opioids [ie. morphine, oxycodone, fentanyl], lidocaine, cannabinoids 
[ie. CBD, THC],) 
o Note: analgesics used as needed are not excluded as long as they are not 
used within 3 days of study screening and enrollment  
3. Any condition in the opinion of the study investigator that would potentially 
confound the results of this study 
4.4 
Study Duration 
 
4.4.1 Approximate Duration of Subject Participation 
Subjects will actively participate in the study for up to one (1) day.  
 
Discontinuation will be based upon investigator’s clinical determination and/or by 
subject decision. All subjects are free to terminate their participation in the study at any 
time, and the details regarding discontinuation will be recorded.   
 
4.4.2 Screen Failures 
If a subject consents to participate in the clinical trial and is not enrolled, they are 
considered a screen failure. A subject can screen fail at any time during Visit 1 prior to 
initiating study procedures. The reason for the subject screen failing must be 
documented in the subject’s source documentation. 
 
4.4.3 Premature Study Treatment Discontinuation 
If a subject decides to discontinue their study participation at any time during Visit 1 and 
after study procedures (post consent) have begun, the reason(s) of study discontinuation 
must be recorded in the subject source documentation.  
 
If the subject discontinued study participation due to an adverse event (AE), the AE must 
be reported, and the subject will be followed up after discontinuation until the AE is 
resolved or considered medically stable by the investigator. 

 
 
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4.4.4 Withdrawal documentation 
The subject may withdraw consent at will at any time. The subject’s request to withdraw 
from the trial must always be respected. In case of withdrawal, the investigator will 
record the reason for subjects’ withdrawal.  
Subject participation in the study may be discontinued for reasons including, but not 
limited to: 
• Withdrawal of subject’s consent 
• Subject preference  
• Decision of the subject’s study investigator 
 
4.4.5 Follow-up on Withdrawn Subjects 
Early discontinuation does not nullify the need to follow AEs until resolution or 
stabilization.  
 
4.4.6 Approximate Duration of Study 
This study is anticipated to be completed within approximately one (1) month, including 
subject enrollment, data collection, and analysis.  
4.5 
Study Visits 
Pre-screening 
Potential subjects whose BMI is 18.5-29.9 kg/m² will be identified in the study 
investigator’s clinic Electronic Medical Record (EMR) and contacted to determine if they 
have a fear/dislike of needles.  
 
Visit 1 (Day1); In-Person Onsite Visit) 
Subjects will be consented and assessed for eligibility to enroll in the study. Subject 
targeted concomitant medications and targeted medical history will be reviewed and 
recorded. The subjects BMI and vital signs will be obtained. 
 
Following confirmation of eligibility, subjects will be enrolled. Subjects will first undergo 
two fingersticks with a 30-gauge Unistik lancing device on pulp of their middle finger. The 
first fingerstick will be performed with no intervention (as per standard of care). 

 
 
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Immediately following the fingerstick, subjects will be provided the VAS pain scale and 
asked to assess their level and pain and document it by circling the level of pain. After 
waiting 5 minutes, the DigiVibe device will be applied to the pulp of the other middle finger 
for 20 seconds, the lancet device will be inserted into the center of the DigiVIbe device, and 
then the second fingerstick will be immediately performed with the DigiVibe device still 
vibrating through the release of the lancing device. Immediately following the fingerstick, 
subjects will be provided the VAS pain scale and asked to assess their level and pain and 
document it by circling the level of pain.  
 
Subjects will then undergo two SC injections with a 30-gauge 4mm needle on the lower 
quadrant of their abdomen at least 2 inches from the belly button. The first SC injection will 
be performed with no intervention (as per standard of care). Immediately following the 
injection, subjects will be provided with the VAS pain scale and asked to assess their level 
and pain and document it by circling the level of pain. After waiting 5 minutes, the DigiVibe 
device will be applied to the other side of the abdomen on the lower quadrant for 20 
seconds and then the second SC injection will be immediately performed with the DigiVibe 
device still vibrating the injection site during the entire injection process. Immediately 
following the SC injection, subjects will be provided the VAS pain scale and asked to assess 
their level and pain and document it by circling the level of pain.  
 
Subjects will then undergo two IM injections. Subjects will undergo alternating assignments 
to either a 25-gauge 1 inch needle or a 30-gauge 1 inch needle in the upper arm deltoid 
muscle. The alternating assignment should be performed separately for the males and 
females so there is an equal distribution of males and females assigned to 25-gauge and 
30-gauge. The alternating assignments must be documented. The first IM injection will be 
performed with no intervention (as per standard of care). Immediately following the 
injection, subjects will be provided with the VAS pain scale and asked to assess their level 
and pain and document it by circling the level of pain. After waiting 5 minutes, the DigiVibe 
device will be applied to the other deltoid muscle for 20 seconds and then the second IM 
injection will be immediately performed with the DigiVibe device still vibrating the injection 
site during the entire injection process. Immediately following the IM injection, subjects 

 
 
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will be provided the VAS pain scale and asked to assess their level and pain and document 
it by circling the level of pain.  
 
Subject AEs will be recorded.  
 
4.6 
Study Procedures 
 
The following procedures will be performed at the times shown in the Study Treatments 
Investigational Medical Products  
• Test Product: DigiVibe Vibrating Anesthetic Device 
• Non-Intervention: Standard of Care 
 Packaging, Labeling, and Storage  
The DigiVibe, Normal Saline, and injection/lancing supplies will be obtained from 
commercial batches and stored in their original packaging without adjustments or 
modifications to the labeling. The investigational product (DigiVibe) will not be masked. 
 
Study Schedule of Activities (SOA): 
 
Demography 
Demography will be recorded at Visit 1 and will consists of date of birth, sex, ethnicity, and 
race. 
 
Targeted Concomitant Medications 
Targeted concomitant medications will be reviewed and recorded at Visit 1. A targeted 
concomitant medication is any NSAID, antiplatelet, anticoagulant, or analgesic treatment 
that the subject received within one (1) month of screening and enrollment into the study. 
All targeted concomitant medications should be documented in the subject’s source 
documents.  
 
Targeted Medical History 

 
 
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Targeted medical history will be reviewed and recorded at Visit 1. Targeted medical history 
includes medical events associated with the use of NSAIDs, antiplatelets, anticoagulants, 
and analgesics.  
 
Vital Signs (height, weight, & blood pressure) 
Subjects will have their height, weight, and blood pressure obtained using calibrated, digital 
devices. Vital signs will be documented in the subject’s source documents.  
 
Fingersticks and Injections (Without Intervention/DigiVibe) 
Subjects will first undergo a fingerstick with a 30-gauge Unistik lancing device on their 
middle finger with no intervention (as per standard of care). For the fingerstick, the 
targeted area of the middle finger will be disinfected with alcohol, the lancing device will be 
pressed firmly against the pulp of the middle finger, and the lancet will be activated. 
 
Subjects will then undergo a SC injection with a 30-gauge 4mm needle on the lower 
quadrant of their abdomen at least 2 inches from the belly button with no intervention (as 
per standard of care). For the SC injection, 0.5 mL of NS will be drawn into the syringe, the 
needle will be replaced with a new 30-gauge 4mm needle, the targeted area of the lower 
abdomen will be disinfected with alcohol, the needle will be inserted at a 90-degree angle, 
the NS will be injected slowly but steadily, and the needle will be withdrawn quickly.  
 
Subjects will then undergo an IM injection with either a 25-gauge 1 inch needle or a 30-
gauge 1 inch needle in upper arm deltoid muscle with no intervention (as per standard of 
care). For the IM injection, 0.5 mL of NS will be drawn into the syringe, the needle will be 
replaced with a new 25-gauge 1 inch needle or 30-gauge 1 inch needle (depending on the 
subject’s assignment (see above), the targeted area of the upper arm deltoid muscle will be 
disinfected with alcohol, the needle will be inserted at a 90-degree angle, the NS will be 
injected slowly but steadily, and the needle will be withdrawn quickly.  
 
Fingersticks and Injections (With DigiVibe) 
 

 
 
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Subjects will undergo a fingerstick with a 30-gauge Unistik lancing device on their middle 
finger using the DigiVibe device. For the fingerstick, the targeted area of the middle finger 
will be disinfected with alcohol, the DigiVibe device will be applied to the pulp of the 
middle finger for 20 seconds, the lancet device will be inserted into the center of the 
DigiVIbe device, and then the second fingerstick will be immediately performed with the 
DigiVibe device still vibrating through the release of the lancing device. 
 
Subjects will then undergo a SC injection with a 30-gauge 4mm needle on the lower 
quadrant of their abdomen at least 2 inches from the belly button using DigiVibe device. 
For the SC injection, 0.5 mL of NS will be drawn into the syringe, the needle will be replaced 
with a new 30-gauge 4mm needle, the targeted area of the lower abdomen will be 
disinfected with alcohol, the DigiVibe device will be applied to the abdomen on the lower 
quadrant for 20 seconds, the needle will be inserted at a 90-degree angle through the 
center of the DigiVibe device (with the DigiVibe device still vibrating), the NS will be 
injected slowly but steadily, and the needle will be withdrawn quickly.  The DigiVibe device 
should continue vibrating on the injection site during the entire injection process until the 
needle is removed.  
 
Subjects will then undergo an IM injection with either a 25-gauge or 30-gauge 1 inch 
needle (depending on their previous assignment) in the upper arm deltoid muscle using 
the DigiVibe device. For the IM injection, 0.5 mL of NS will be drawn into the syringe, the 
needle will be replaced with a new 25-gauge or 30-gauge (depending on their assignment) 
1 inch needle, the targeted area of the upper arm deltoid muscle will be disinfected with 
alcohol, the DigiVibe device will be applied to the deltoid muscle for 20 seconds, the needle 
will be inserted at a 90-degree angle through the center of the DigiVibe device (with the 
DigiVibe device still vibrating), the NS will be injected slowly but steadily, and the needle 
will be withdrawn quickly. The DigiVibe device should continue vibrating on the injection 
site during the entire injection process until the needle is removed.  
 
Visual Analog Scale (VAS) 
Subjects will be provided with a paper copy of the VAS, a validated scale that allows 
subjects to measure their pain on a visual horizontal grading scale of zero (0) to ten (10).  

 
 
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Subjects will use the VAS to provide their subjective measure of their pain level 
immediately following each fingerstick and injection for a total of six (6) completed scales.  
 
Review AEs 
AEs will be collected during the visit, which includes any new clinically significant sign or 
symptom or any clinically significant worsening of a pre-existing sign or symptom. The 
definitions of AEs and serious AEs (SAEs) are provided below.  
 
Study Exit 
After the procedures in the visit are complete, the subject is exited from the study.   
 
4.7 
Study Treatments 
4.7.1 Investigational Medical Products  
• Test Product: DigiVibe Vibrating Anesthetic Device 
• Non-Intervention: Standard of Care 
 Packaging, Labeling, and Storage  
The DigiVibe, Normal Saline, and injection/lancing supplies will be obtained from 
commercial batches and stored in their original packaging without adjustments or 
modifications to the labeling. The investigational product (DigiVibe) will not be masked. 
 
4.8 
Study Schedule of Activities (SOA) 
 
Procedure 
Screening/ Enrollment  
Visit 1/ Day 1 
In-Person 
Informed Consent 
X 
Inclusion/Exclusion criteria 
X 
Demographics 
X 
Vital Signs (height, weight, & BP) 
X 
Targeted Medical History 
X 

 
 
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Targeted Concomitant Medications 
X 
Fingerstick without DigiVibe 
X 
Subject VAS Pain Scale (post fingerstick without 
DigiVibe) 
X 
Subcutaneous Injection without DigiVibe 
X 
Subject VAS Pain Scale (post subcutaneous injection 
without DigiVibe) 
X 
Intramuscular Injection without DigiVibe 
X 
Subject VAS Pain Scale (post intramuscular injection 
without DigiVibe) 
X 
Fingerstick with DigiVibe 
X 
Subject VAS Pain Scale (post fingerstick with DigiVibe) 
X 
Subcutaneous Injection with DigiVibe 
X 
Subject VAS Pain Scale (post subcutaneous injection 
with DigiVibe) 
X 
Intramuscular Injection with DigiVibe 
X 
Subject VAS Pain Scale (post intramuscular injection with 
DigiVibe) 
X 
Adverse events 
X 
Study Exit 
X 
Data Entry 
X 
 
4.9 
Data Analysis 
 
4.9.1 Statistical Analysis Plan 
Demographics and baseline characteristics of study subjects will be summarized, as will 
VAS pain scores for the intervention (DigiVibe) and standard care. The primary analysis 
will be a paired t-test or Wilcoxon signed-rank test (depending on normality of VAS 
scores) to compare pain scores between standard care and DigiVibe. These tests will be 
performed individually for each of the injection sites (fingerstick, SC, IM).  

 
 
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4.9.2 Statistical Power and Sample Size Considerations 
For any of the three (3) injection sites individually, a sample size of 20 patients achieves 
≥80% power to detect a mean of paired differences of 1.0 with an estimated standard 
deviation of differences of 1.5 and with a significance level (α) of 0.05 using a two-sided 
paired t-test. A smaller difference (e.g., 0.75) would be detectable with power ≥88% at 
an α=0.05 using the same test, if the standard deviation is 1.0. 
 
4.10 Data Management 
 
4.10.1 Data Collection and Storage  
Data required by the protocol will be collected using a data collection form created by the 
investigative site. The investigator has ultimate responsibility for the collection and 
reporting of all clinical data entered on the data collection form. Excel worksheets will be 
used to create the data repository for the analysis data set which will be de-identified and 
employ range checking derived from the study data dictionary. Final data merges for 
analysis will be performed with statistical analysis system (SAS) software. Electronic data 
will be stored on encrypted drives and backed up routinely to a secure server. At the End 
of Study completion, all electronic data will be stored on a password protected universal 
serial bus (USB) flash drive and archived with study documents.  
 
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). 
All physical records will be kept in a locked file cabinet.  
 
4.10.2 Records Retention  
The investigator must agree to archive the study documentation (both electronic and 
paper-based records) in an archive after completion or discontinuation of the trial. The 
investigator should not destroy any documents without prior permission from Suthe 
Dermal. If the investigator cannot archive the documents at the trial site, they should 
notify Suthe Dermal. At the conclusion of this study, data from this study will be archived 
for 2 years for possible use in future research studies.   
 

 
 
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5 
SAFETY MONITORING  
 
5.1 
Adverse Event Reporting 
 
Clinical AEs and SAEs will be monitored from signing of the ICF until completion of all 
study procedures are completed. All AEs and SAEs will be reported to an Investigator 
regardless of whether they are considered study-related.  The date and time of onset 
and outcome, seriousness, intensity, action taken, and causality to study treatment will 
be assessed by a study investigator.    
 
5.2 
Definitions 
 
An adverse event (AE) is any untoward, undesired, or unplanned event in the form of 
signs, symptoms, disease, or laboratory or physiological observations occurring in a 
person given a test article or in a clinical study. This includes a clinically significant 
worsening of a concomitant illness and clinical laboratory abnormalities which are 
clinically significant, i.e. an abnormality that suggests a disease and is of a severity that 
requires active management. The event does not need to be causally related to the 
device or clinical study. 
 
The following definitions are used when assessing the intensity of an AE: 
• Mild: no or transient symptoms, no interference with the subject’s daily 
activities. 
• Moderate: marked symptoms, moderate interference with the subject’s daily 
activities. 
• Severe: considerable interference with the subject’s daily activities; 
unacceptable. 
 
The following definitions are used when assessing the causality (relationship) of an AE: 
• Related: A causal relationship between the study treatment and the AE is a 
reasonable possibility. The Investigator must further qualify the degree of 
certainty as “possible” or “probable.” 

 
 
21 
 
• Possible: A causal relationship is conceivable and cannot be dismissed.  
• Probable: Good reason and sufficient documentation to assume a causal 
relationship. 
• Not Related: A causal relationship between the study treatment and the AE is not 
a reasonable possibility. 
 
Items to be considered when assessing the relationship of an AE to the study treatment 
are: 
• Temporal relationship of the onset of the event to the initiation of the study 
treatment; 
• The course of the event, considering especially the effect of the discontinuation of 
study treatment or the reintroduction of study treatment, as applicable; 
• Whether the event is known to be associated with the study treatment or with 
other similar treatments; 
• The presence of risk factors in the study subject known to increase the occurrence 
of the event; and, 
• The presence of non-study treatment-related factors that are known to be 
associated with the occurrence of the event. 
 
The following definitions are used when assessing the outcome of an AE: 
• Recovered/resolved: The subject has fully recovered, or by medical or surgical 
treatment the condition has returned to the level observed at the first trial-related 
activity after the subject signed the ICF. 
• Recovering/resolving: The condition is improving, and the subject is expected to 
recover from the event. This term is only applicable if the subject has completed 
the trial or has died from another AE. 
• Recovered/resolved with sequelae: The subject has recovered from the 
condition, but with lasting effect due to a disease, injury, treatment or 
procedure. If a sequela meets an SAE criterion, the AE must be reported as an 
SAE.  
• Not recovered/not resolved: The condition of the subject has not improved, and 

 
 
22 
 
the symptoms are unchanged, or the outcome is not known. 
• Unknown: This term is only applicable if the subject is lost to follow-up. 
 
SAEs are any untoward medical occurrence affecting the pain site: 
• Results in death; 
• Is life-threatening (i.e., the subject was at immediate risk of death from the AE as 
it occurred; this does not include an event that, had it occurred in a more severe 
form or was allowed to continue, might have caused death); 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity; 
• Is a congenital anomaly/birth defect; 
• Is a medically important event. 
 
5.3 
Recording and Reporting 
A subject’s AEs and SAEs will be recorded and reported from the signing of the informed 
consent form until the subject’s final study procedures are completed. All SAEs must be 
reported to the PI. 
6 
ADMINISTRATIVE PROCEDURES 
6.1.1 
Changes to the Protocol 
There are to be no changes to the protocol without written approval from the 
Investigators and sponsors. Protocols will be followed as written. 
 
Any change to the protocol requires a written protocol amendment or administrative 
change that must be approved before implementation by the sponsor and IRB. 
Amendments specifically affecting the safety of subjects, the scope of the investigation, 
or the scientific quality of the study require additional approval by the applicable IRBs of 
all investigational sites. These requirements should in no way prevent any immediate 
action from being taken by the Investigator or by the Sponsor in the interest of 
preserving the safety of all subjects included in the study. If an immediate change to the 
protocol is felt by the Investigator to be necessary for safety reasons, the sponsor and 

 
 
23 
 
IRB must be notified promptly.   
 
Changes affecting only the administrative aspects of the study do not require formal 
protocol amendments or IRB approval, but the IRB must be kept informed of such 
changes. In these cases, the Principal Investigator will send a letter to the IRB detailing 
such changes. 
 
6.1.2 
Adherence to the Protocol 
The Investigators will conduct the study in strict accordance with the protocol, which has 
been written to enable the Investigator’s compliance with Good Clinical Practices. 
 
6.1.3 
Monitoring Procedures 
 Responsibilities of the Principal Investigator 
The principal investigator is required to ensure compliance with all procedures required by 
the clinical trial protocol and agrees to provide reliable data requested by the clinical trial 
protocol in an accurate and legible manner. The principal investigator may delegate other 
individuals as they deem appropriate as sub-investigators to assist in the conduct of the 
clinical trial. The sub-investigators will work under the responsibility of the principal 
investigator. The principal investigator will provide them with a copy of the clinical trial 
protocol and all necessary information. 
 Responsibilities of the Monitor 
The monitor of this clinical trial is responsible for taking all reasonable steps to ensure the 
proper conduct of the clinical trial regarding ethics, protocol compliance, and integrity and 
validity of the data recorded. Thus, the main duty of the monitor is to help the principal 
investigator maintain a high level of ethical, scientific, technical and regulatory quality in all 
aspects of the clinical trial.  
Throughout the clinical trial, the monitor will contact the site through monitoring visits or 
phone calls to review study progress, investigator and patient compliance with the 
protocol, and any study-related issues. The monitoring visits will include, but not be limited 
to, review of the following aspects: patient ICFs, patient recruitment and follow-up, SAE 

 
 
24 
 
documentation and reporting, AE documentation, compliance with the study protocol, and 
quality of data. The monitor must check the data collected against the source documents.  
  
7 
PUBLICATION PLAN   
Results from this research (without any subject identifiers) may be submitted for journal 
publication or presentation at national meetings. Important findings may be submitted to 
conferences and for publication in peer-reviewed scientific journals. The identity of the 
subjects may not be disclosed, unless required by law, to any persons not immediately 
involved in the study or the study procedures. 
 
8 
REFERENCES  
1. Campbell TS, Johnson JA, Zernicke KA. Gate Control Theory of Pain. In: Encyclopedia 
of Behavioral Medicine. Cham: Springer International Publishing; 2020.  
2. Smith K, Comite S, Balasubramanian S, Carver A, Liu J. Vibration Anesthesia: A 
Noninvasive Method of Reducing Discomfort Prior to Dermatologic Procedures. 
Dermatology Online Journal. 2004. 
3. Weeks D, Faillace J. Vibratory Anesthesia’s effect on pain perception in upper 
extremity corticosteroid injections. US National Library of Medicine. July 2022. 
4. Shaefer JR, Lee SJ, Anderson NK. A Vibration Device to Control Injection Discomfort. 
Compend Contin Educ Dent. 2017 Jun;38(6):e5-e8. PMID: 28586233.