Post-operative Pain Following Treatment Using the Gentlewave System
Phase: NA
Conditions: Root Canal Infection, Endodontic Disease, Endodontic Inflammation, Post-Operative Pain
Sponsor: University of Minnesota

PROTOCOL TITLE: Post-operative Pain Following Treatment Using the Gentlewave System 
VERSION DATE: 01-08-2018
PROTOCOL TITLE: 
Post-operative Pain Following Treatment Using the Gentlewave System 
PRINCIPAL INVESTIGATOR or FACULTY ADVISOR: 
Ronald Ordinola-Zapata, DDS, PhD, MS 
Faculty Advisor 
Division of Endodontics 
612-624-2661 
rordinol@umn.edu 
STUDENT INVESTIGATOR: 
Jeffrey Heyse Jr DMD 
Resident 
Graduate Endodontics 
heyse005@umn.edu 
Jonas Dale DDS 
Resident 
Graduate Endodontics 
Dalex145@umn.edu 
VERSION NUMBER/DATE: 
Version 001 / 05-07-2018 
 
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PROTOCOL TITLE: Post-operative Pain Following Treatment Using the Gentlewave System 
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REVISION HISTORY 
NOTE: Leave this sec0on blank for the ini0al submission. The revision history should be 
documented for modiﬁca0ons to approved studies. 
Revision #
Version Date
Summary of Changes
Consent Change?
01
08-27-2019
Updated Primary inves0gator and 
student inves0gator, Changed VAS to 
NRS to reﬂect the correct name of the 
scale being used, changed sample size, 
changed procedures involved to reﬂect 
mul0ple appointments and 0ming of 
pain assessment, updated inclusion 
criteria
yes
02
10-3-2019
Updated student investigator to add 
Dr Dale. Minor changes to  study 
design, primary objective, sample 
size, duration of appointments to 
reflect collecting data from only 
symptomatic patients.
 
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PROTOCOL TITLE: Post-operative Pain Following Treatment Using the Gentlewave System 
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Table of Contents 
1.
Objectives 
 
..................................................................................................................6
2.
Background 
 
...............................................................................................................6
3.
Study Endpoints/Events/Outcomes 
 
...........................................................................7
4.
Study Intervention(s)/Investigational Agent(s) 
 
.........................................................8
5.
Procedures Involved 
 
..................................................................................................8
6.
Data and Specimen Banking N/A 
 
............................................................................11
7.
Sharing of Results with Participants N/A 
 
................................................................11
8.
Study Population 
 
.....................................................................................................11
9.
Vulnerable Populations 
 
...........................................................................................12
10.
Local Number of Participants 
 
.................................................................................13
11.
Local Recruitment Methods 
 
....................................................................................13
12.
Withdrawal of Participants 
 
......................................................................................13
13.
Risks to Participants 
 
................................................................................................14
14.
Potential Benefits to Participants 
 
............................................................................15
15.
Statistical Considerations 
 
........................................................................................15
16.
Confidentiality 
 
.........................................................................................................16
17.
Provisions to Monitor the Data to Ensure the Safety of Participants 
 
......................16
18.
Provisions to Protect the Privacy Interests of Participants 
 
......................................17
19.
Compensation for Research-Related Injury 
 
............................................................17
20.
Consent Process 
 
.......................................................................................................18
21.
Setting 
 
......................................................................................................................18
22.
Multi-Site Research 
 
.................................................................................................19
23.
Resources Available 
 
................................................................................................19
24.
References .............................................................................................................19
 
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PROTOCOL TITLE: Post-operative Pain Following Treatment Using the Gentlewave System 
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ABBREVIATIONS/DEFINITIONS 
•
AED: Automated External Deﬁbrillator 
•
AHC-IS: Academic Health Center – Informa0on Systems 
•
Ca(OH)2: Calcium Hydroxide 
•
CBCT: Cone Beam Computed Topography 
•
EDTA: Ethylenediaminetetraace0c Acid 
•
NaOCl: Sodium Hypochlorite 
•
VAS: Visual Analog Scale 
•
NRS: Numeric Ra0ng Scale 
 
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PROTOCOL TITLE: Post-operative Pain Following Treatment Using the Gentlewave System 
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STUDY SUMMARY 
Study Title
Post-operative pain following treatment using the 
Gentlewave system
Study Design
Confirmation of pre-operative pain (symptomatic 
status) will be determined by having the patient 
record their pain level to percussion at the initial 
examination using the NRS scale. Additionally, the 
force required to cause pre-operative pain to biting 
will be recorded using a digital occlusal force meter.   
The NRS will consist of a 100mm line where 0 
equals ‘no pain’ and 100 equals the ‘worst pain 
imaginable’. Patients will be divided into one of two 
treatment groups: 1) standard root canal cleaning and 
shaping procedures (control group) or 2) the 
Gentlewave technique, which uses sonic energy and 
irrigation for cleaning of the root canal system 
(research group). Patient demographics, anesthesia, 
cleaning and shaping instruments, irrigation 
technique, and obturation method and material will 
be recorded, along with the number of appointments, 
detailed notes of treatment rendered, and the 
occurrence of over-instrumentation or overfill of 
obturation material. Following the first and final 
appointment, patients will be given the same NRS to 
take home and record their level of pain at 6, 24, 72, 
and 168 hours post-treatment.
Primary Objective
To determine whether treatment with the Gentlewave 
system will significantly decrease the occurrence and 
of post-operative pain in symptomatic patients 
following endodontic treatment. 
Secondary Objective(s)
If post-operative discomfort should occur, to 
determine the severity based on an NRS for pain 
assessment. 
Research Intervention(s)/
Investigational Agents
Gentlewave system for root canal disinfection
Scientific Assessment
Not required, Minimial Risk Study
IND/IDE # (if applicable)
N/A
IND/IDE Holder
N/A
 
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1.
Objectives 
1.1. Purpose: The purpose of this study is to determine whether a new treatment 
modality for cleaning and disinfecting the root canal system will 
significantly affect the occurrence and severity of post-operative pain in 
symptomatic patients. 
2.
Background 
2.1. Significance of Research Question/Purpose: To further the scientific 
discussion and recognize treatment modalities that may eliminate the 
occurrence of post-operative pain. 
2.2. Preliminary Data: N/A 
2.3. Existing Literature: Once a tooth reaches a level of inflammation where 
healing can no longer occur or when the pulp space begins to go through 
necrosis, root canal treatment is indicated. The goal of root canal therapy is 
to clean, shape, disinfect, and obturate all canal systems within the tooth. 
Schilder’s mechanical and biological objectives for cleaning and shaping 
includes: preparing a continuous tapering root canal funnel from access to 
apex, cross-sectional diameters should be wider at every point as you move 
coronally, the preparation should occupy as may planes as presented by the 
original canal and should follow the shape of the original canal, the apical 
foramen should remain in it is original spatial relationship to bone and to 
root surface, the apical opening should be kept as small as practical in all 
cases, complete cleaning and shaping in one appointment, procedures should 
be confined to the roots themselves, necrotic debris should not be forced 
Investigational Drug Services 
# (if applicable)
N/A
Study Population
The target population of the study includes patients 
needing endodontic treatment in the University of 
Minnesota Graduate Endodontics clinic, ages 18+. 
Patients with teeth that have root apices in the 
maxillary sinus, teeth with immature root apices, and 
teeth with insufficient coronal tooth structure will be 
excluded.
Local Sample Size (number of 
participants recruited locally)
Approximately 150  participants will be recruited. 
Dr Grigsby’s original study was approved for 50 pts, 
our study will break symptomatic patients into 1 of 2 
symptomatic categories: necrotic or vital pulps. So 
50 participants in each group, 100 total new patients 
will be recruited.
 
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beyond the foramina, all tissues should be removed from root canal space, 
and sufficient space for intracanal medicaments and irrigation should be 
created (1). Peters added to these objectives in creating his own basic 
objectives for cleaning and shaping that include: removing infected soft and 
hard tissue, giving disinfecting irrigants access to the apical canal space, 
creating space for the delivery of intracanal medicaments and subsequent 
obturation, and retaining the integrity of radicular structures (2). 
Traditionally, the standard protocol for cleaning and shaping is completed 
using hand or rotary files. Various file systems are used to prepare root canal 
systems to the parameters set by Schilder’s and Peters’ principles. In 
addition, it is important to keep necrotic debris within the canal space as a 
means of preventing post-operative pain and flare-ups (3). Siqueira 
discovered that the factors that are commonly responsible for post-operative 
or interappointment pain include mechanical preparation and obturation 
beyond the apex, bacterial insults not present in the primary infection, and 
chemical extrusion of irrigant materials beyond the apex (3). Post-operative 
pain can occur hours to days following root canal procedures. Acute 
inflammation due to the aforementioned etiologic factors is the chief cause 
of post-operative pain. According to Gotler et al, post-operative pain 
typically occurs at a higher severity and incidence in vital teeth and 
retreatments as opposed to non-vital teeth (4). Irrigation dissolves organic 
material and kills microbes. It also helps prevent the binding of instruments, 
improves the cutting effectiveness of files, dissolves tissue, and cools the 
instrument and tooth (5). The most common endodontic irrigant is sodium 
hypochlorite (6). Sodium hypochlorite is an alkaline fluid with a pH of 
approximately 11-12. It hydrolyzes proteins and causes hemolysis of red 
blood cells which leads to the dissolution of vital, as well as necrotic tissue. 
Upon contact of organic debris, hypochlorus acid forms which disrupts 
bacterial metabolism by oxidizing the sulfhydryl group of bacterial 
enzymes. With the use of such a caustic material, there is always the 
possibility of complications. Most hypochlorite accidents occur because of 
inaccurate working length determination, iatrogenic widening of the apical 
foramen, lateral perforation, or wedging of the irrigation needle. Once 
irrigant is extruded beyond the apex, severe pain, uncontrollable bleeding, 
immediate swelling, and bone and tissue necrosis can occur (7&8). Standard 
endodontic treatment protocol includes irrigation with 5.25% sodium 
hypochlorite between each file used for cleaning and shaping with a final 
ultrasonic activation of the sodium hypochlorite for 30 seconds per canal. 
Lastly, there is a one minute soak of 17% EDTA to remove the layer of 
debris created from cleaning and shaping (5).  
3.
Study Endpoints/Events/Outcomes 
 
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3.1. Primary Endpoint/Event/Outcome: The primary outcome of this study is to 
determine whether treatment with the Gentlewave system will significantly 
decrease the occurrence of post-operative pain with endodontic treatment.  
3.2. Secondary Endpoint(s)/Event(s)/Outcome(s): The secondary outcome is to 
determine the intensity of pain, should it occur, based on a NRS pain 
assessment.  
4.
Study Intervention(s)/Investigational Agent(s) 
4.1. Description: The Gentlewave system is a FDA cleared root canal irrigation 
device that uses internally degassed distilled water, 3% NaOCl, and 8% 
EDTA to allow for a more thorough cleaning within the tooth (8). The 
system uses broad spectrum acoustic energy to create hydrodynamic 
cavitation and thousands of micro bubbles that create powerful shear forces. 
The fluids work to remove necrotic tissue, debris, biofilm, and bacteria 
while leaving dentin intact and preserving tooth structure. The cleaning and 
shaping protocol when using the Gentlewave system requires the clinician to 
prepare all canals within a tooth to a minimum of size 20 before using the 
Gentlewave system for irrigation. The Gentlewave irrigation replaces the 
NaOCl ultrasonic activation and EDTA steps of the standard endodontic 
protocol. Use of the Gentlewave system is contraindicated in teeth with 
immature apices, teeth with insufficient coronal structure, and teeth with 
root apices extending into the maxillary sinus.  
4.2. Drug/Device Handling: The Gentlewave device will be stored in the 
Graduate Endodontics research laboratory and any treatment fluids 
specifically for research purposes will be locked and labeled for use at 
designated times. An inventory log of when and how much treatment fluids 
used will be kept and updated after each participant treatment.  
4.3. Biosafety: N/A  
4.4. Stem Cells: N/A 
5.
Procedures Involved 
5.1. Study Design: Patients will be asked to indicate their peak pain level in the 
twenty-four hours prior to the appointment using a numeric rating scale 
(NRS). The NRS scale will consist of a 100mm line where 0 equals ‘no 
pain’ and 100 equals the ‘worst pain imaginable’. Patients will be divided 
into one of two treatment groups, either standard cleaning protocol or 
Gentlewave irrigation. Patient demographics, anesthesia, cleaning and 
shaping instruments, irrigation technique, and obturation method and 
material will be recorded, along with extent of treatment rendered, and the 
occurrence of over-instrumentation or overfill of obturation material. 
 
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Following the first appointment, patients will be given the same NRS 
assessment to take home and asked to record their level of pain at 6, 24, 72, 
and 168 hours post-treatment. 
5.2. Study Procedures: 
•
Procedures that will be performed regardless of whether research were 
being conducted include diagnostic examination and radiographic 
examination/interpretation. Diagnostic examination includes 
sensibility testing of the tooth/teeth in question, determination of 
whether or not a crack, fracture, or non-endodontic pathology exists, 
and determination of the etiology of endodontic pathology. Diagnostic 
exam procedures include thermal testing using either Endo Ice 
Refrigerant spray or heated gutta-percha, electric pulp testing device if 
thermal testing is inconclusive, percussion testing using the handle of 
a mouth mirror and digital palpation of gingival area near the tooth/
teeth in question. Periodontal examination will also be performed for 
probing depths and mobility. Transillumination and methylene blue 
staining may be performed if a crack or fracture is suspected.  
Radiographic examination includes at least two periapical radiographs 
for posterior teeth and one periapical radiograph for anterior teeth. A 
limited field of view CBCT may be taken if necessary.  
•
Confirmation of pre-operative pain (symptomatic status) will be 
determined by having the patient record their pain level to percussion 
at the initial examination using the NRS scale. Additionally, the force 
required to cause pre-operative pain to biting will be recorded using a 
digital occlusal force meter.   
•
During the treatment portion of research, the tooth needing treatment 
will be sufficiently anesthetized with local anesthetic to undergo the 
procedure pain-free. A rubber dam will be placed isolating the tooth in 
question and one tooth adjacent to that tooth both mesially and 
distally. The pulp chamber will be accessed and prepared for straight 
line access to all canal orifices. During access, all caries and defective 
restorations will be removed. If there is a defective crown, it will be 
removed prior to rubber dam isolation. Hand files and electronic apex 
locators will be used to determine the working length of each files. 
Working length will be verified using a periapical radiograph. At this 
point is where the two treatment groups will diverge.  
•
For the standard protocol (control) group, following working length 
determination, all canals will be cleaned and shaped using rotary files 
to at least a size 20.04 canal size and to within 0.5 to 1 mm short of the 
apical terminus. Appropriate final canal size will be determined by the 
clinician treating the patient.  Between each file, 5.25% NaOCl will be 
 
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used to disinfect and wash the canals of debris. After the canal has 
been cleaned and shaped to 20.04, sodium hypochlorite will be 
passively activated using an ultrasonic instrument for 30 seconds per 
canal. Next, each canal will soak in 17% EDTA for 1 minute, will be 
rinsed in 5.25% NaOCl, and finally undergo a final rinse of 95% 
ethanol. Canals will be filled with Ca(OH)2 and a temporary 
restora0on will be placed with a coUon pellet and restora0ve material 
of the clinician’s choice. All of these steps make up our standard 
protocol and would be performed whether research is being conducted 
or not. 
•
For the Gentlewave treatment group, the standard protocol will be 
followed until working lengths are determined. Each canal will be 
shaped to a canal size of 20.04 or 20.06 and to 1mm short of the apical 
terminus. An occlusal platform will be prepared to allow Gentlewave 
treatment of the tooth using the Kool-dam material recommended by 
Sonendo. The Gentlewave system will be held on the tooth by the 
clinician and will cycle through five minutes of 3% sodium 
hypochlorite, two minutes of 8% EDTA, and a final rinse of distilled 
water. Canals will be filled with Ca(OH)2 and a temporary restora0on 
will be placed with a coUon pellet and restora0ve material of the 
clinician’s choice. If the research were not conducted, these patients 
would be treated using the standard protocol as above. 
•
Pain Management: As both arms include standard of care treatment, 
pain management will be the same recommendation as our standard, 
non-research related treatment. Recommendations for pain 
management include: 600mg Ibuprofen every 6 hours for pain. If 
additional pain relief is needed, patients are instructed to add 
500-650mg Acetaminophen every 6 hours. If these medicines are 
necessary, participants will be instructed to record which medicines 
were taken, the amount, at which times, and how often. This will be 
returned along with the NRS pain assessment. 
•
Following the first  and final appointment, regardless of procedure, 
participants will be given the same NRS pain assessment from 
pretreatment to take home and asked to record their level of pain at 6, 
24, 72, and 168 hours post-treatment.  Participants will be given an 
envelope with prepaid postage to return the pain assessment form to 
the graduate endodontics office. 
•
Should a participant’s pain assessment form not be returned, a phone 
call will be placed to remind the participant to return the form. 
 
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•
The Gentlewave system is a FDA cleared root canal irrigation device 
that is used to remove necrotic tissue, debris, biofilm, and bacteria 
while leaving dentin intact and preserving tooth structure. The 
Gentlewave irrigation replaces the NaOCl ultrasonic activation and 
EDTA steps of the standard protocol. 
•
The data to be collected include patient demographics, pretreatment/
posttreatment NRS pain assessment recordings, anesthetic technique/
amount, cleaning and shaping instruments, irrigation technique 
(standard vs Gentlewave), and obturation method/material will be 
recorded. The occurrence of over-instrumentation or overfill of 
obturation material will also be recorded. 
•
The total time commitment for all participants, regardless of arm 
assignment, will 4+ hours of treatment time and 5 minutes a day for 14 
days to record pain levels.  
5.3. Study Duration:  
•
The anticipated duration for enrolled participants is the amount of 
time to complete treatment (multiple visit treatment) and the 14 days 
(7 days after 1st visit and 7 days after final visit) following treatment 
during self-evaluation of post-operative pain. 
•
The anticipated time to complete all study procedures, follow-up, and 
data analysis is projected to be 12-15 months.  
5.4. Individually Identifiable Health Information: The study will involve access 
to individually identifiable health information. The purpose of access is to 
ensure patients are treated safely and are not administered any medication/
anesthetic the patient may be allergic to or that may be contraindicated for 
use with any medication they may be currently taking.  
5.5. Use of radiation: The study will involve the use of radiation in the 
completion of endodontic treatment. This involves taking multiple periapical 
radiographs and possibly limited field of view cone beam computed 
tomography. 
5.6. Use of Center for Magnetic Resonance Research: N/A  
6.
Data and Specimen Banking N/A 
7.
Sharing of Results with Participants N/A 
8.
Study Population 
8.1. Inclusion Criteria: The target population of the study includes patients 
needing endodontic treatment in the University of Minnesota Graduate 
Endodontics clinic, ages 18+. Those with an apical diagnosis of 
symptomatic apical periodontitis. Vulnerable populations that will be 
 
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included in the study are members of the military and those individuals from 
an undervalued or disenfranchised social group.  
8.2. Exclusion Criteria: Patients with teeth that have root apices in the maxillary 
sinus, teeth with immature root apices, and teeth with insufficient coronal 
tooth structure will be excluded. For the purposes of this study children, 
pregnant women, prisoners, and adults lacking the capacity to consent will 
be excluded.  
8.3. Screening: Screening will be completed during the participant’s consultation 
appointment for endodontic treatment.  
9.
Vulnerable Populations 
9.1. Vulnerable Populations:  
☐ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ Adults lacking capacity to consent and/or adults with diminished capacity 
to consent, including, but not limited to, those with acute medical 
conditions, psychiatric disorders, neurologic disorders, developmental 
disorders, and behavioral disorders 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
☒ Undervalued or disenfranchised social group 
☒ Members of the military 
☒ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☐ None of the above 
9.2. Additional Safeguards: Inclusion of these selected groups does not represent 
any additional safety issues. There would be no medical or dental safety 
issue that would warrant their exclusion. The safeguard in place to protect 
 
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their rights includes nondiscriminatory practices and equal presentation of 
study participation and treatment options.  
10.
Local Number of Participants 
10.1. Local Number of Participants to be Consented: The approximate number of 
participants requested is 150. 34, or 17 per treatment group, is the lowest 
number that will give an 80% power to detect a mean difference between the 
two groups of 1 standard deviation. (Dr Heyse and Dr Dale will each 
analyze a subcategory of symptomatic patients: Necrotic symptomatic teeth 
or Vital symptomatic teeth). Requesting 150 participants allows for greater 
clinical meaningfulness and accounts for possible dropouts.  Randomization 
order for each arm of the study will be 1 to 1. 
11.
Local Recruitment Methods 
11.1. Recruitment Process: Participants will be recruited during their consultation 
appoint at the University of Minnesota Graduate Endodontics clinic. 
Advertisements will not be publicly posted.  
11.2. Identification of Potential Participants: Potential participants will be 
recruited from the Graduate Endodontics patient population and will be 
identified on their consultation exam and rightness of fit based on their 
demographics and tooth morphology and anatomy. Supplemental 
investigators will make the initial contact and upon participant signage of 
consent forms will be made known to the primary investigator.  
Confirmation of participation will be known when the patient signs a 
consent form.  
11.3. Recruitment Materials: After being identified by a member of the research 
team, the potential participant will be given recruitment material which is a 
FAQ sheet that they can take home and read should they need more time to 
consider the invitation to participate.  
11.4. Payment: No gifts, payments, compensation, reimbursement, or services 
without charge will be provided to the participants for participating in the 
research. 
12.
Withdrawal of Participants 
12.1. Withdrawal Circumstances: Should patients have an occurrence that will 
eliminate their eligibility for root canal therapy, i.e. an unforeseen crack or 
fracture.  
12.2. Withdrawal Procedures: For research in which it is determined to be 
appropriate to document the withdrawal of a subject, such documentation 
could specify: 
 
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• Documentation of whether the withdrawal of the participant resulted from 
a decision by the participant or by the investigator, and the reasons for the 
withdrawal, if known. 
• Whether the withdrawal was from all components of the research study or 
just the primary interventional component.  
• Should any participant want to withdraw from procedures, the participant 
will be debriefed on which arm of the procedure they were assigned to. An 
offer to complete treatment via other standard treatment options will be 
extended. Also, following treatment the participant will not be asked to 
complete the pain scale assessment, but will have the standard 6 month 
recall to assess healing. The Office of Human Research Protections also 
recommends that the investigator explain to the participant the importance 
of obtaining follow-up safety data about the participant.  If the participant 
agrees, research activities involving these other types of participation for 
which the participant previously gave consent will continue. Should a 
participant wish to seek treatment elsewhere, a list of possible 
endodontists will be furnished. Data collection will terminate at the point 
of withdrawal.  
12.3. Termination Procedures: Procedures will be terminated should the patient 
want to withdraw or if there is a pathological discovery that would deem the 
tooth in question non-restorable, after treatment has begun. Should a 
participant wish to seek treatment elsewhere, a list of possible endodontists 
will be furnished. Should the tooth be deemed non-restorable, referral to the 
University’s Oral & Maxillofacial Surgery graduate clinic will be provided. 
Data will not be used following termination.  
13.
Risks to Participants 
13.1. Foreseeable Risks:  
All risks listed below are associated with both arms of the study. 
• Post-operative discomfort or sensitivity: Recommendation of 600mg 
ibuprofen or a combination of 600mg ibuprofen plus 1000mg 
acetaminophen every 6 hours (Menhinick) 
• Restrictive mouth opening: Recommendation of home remedies for 
limited mouth opening and trismus following extended periods of mouth 
opening. 
• Jaw muscle spasm or cramps: This risk can be lessened by using post-
procedure massages, heat and ice packs, as well as anti-inflammatory 
analgesics.  
 
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• Temporomandibular joint difficulty: This risk can be lessened by using 
post-operative massages, heat and ice packs, as well as anti-inflammatory 
medicines.  
• Non-healing of the tooth: Following treatment, the tooth and 
symptomatology will be monitored for resolution. Should symptoms not 
resolve, the next phase of treatment (i.e. root end resection) will be 
discussed with the participant. 
• Damage to restorations: If a restoration is damaged beyond the 
investigator’s ability to repair, the proper referral will be made.  
• Reaction to local anesthetic: Correct administration technique and 
continual evaluation 
• Uncontrollable Bleeding: All attempts will be made to arrest bleeding. If 
bleeding cannot be controlled then a Ca(OH)2 medicament can be placed in 
the tooth and temporary restoration material placed. A subsequent 
appointment will be scheduled. 
• Separation of instruments within root canals: Every attempt will be 
made to remove the separated instrument. If it cannot be removed then an 
attempt will be made to disinfect and obturate beyond it. The participant 
will be monitored for healing. 
• Over-instrumentation or over-obturation of root canals: The working 
length of the canals will be determined by electronic apex locators and 
verified using periapical radiographs.  
• Numbness or paresthesia: The local anesthetic agents used to gain 
anesthesia have relatively low risk of causing numbness or paresthesia. 
Risk specific to Gentlewave treatment 
•
Increased sensitivity due to backpressure during machine operation: 
Profound anesthesia, and adequate access opening preparation to 
eliminate possible back pressure during operation.  
13.2. Reproduction Risks: N/A 
13.3. Risks to Others: N/A 
14.
Potential Benefits to Participants 
14.1. Potential Benefits: No direct benefit to individual participants, other than 
necessary root canal treatment 
15.
Statistical Considerations 
15.1. Data Analysis: To examine the research question, a two-sample t test will be 
conducted to determine if mean differences exist on post-operative pain 
 
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following treatment with the Gentlewave system and post-operative pain 
following standard endodontic treatment. Two-sample t test, with a 
significance level of 0.05, is an appropriate statistical analysis if each of the 
two samples can be matched on the pain measurements at 6, 24, 72, and 168 
hours following the completion of treatment. A linear mixed effects model 
will be used to compare the groups across time. Also, descriptive statistics 
will be used for patient demographics and characteristics. 
15.2. Power Analysis: A sample size of 17 per group will give an 80% power to 
detect a mean difference between the two groups of 1 standard deviation. 
This sample size selection and power analysis is based off of previous 
studies 
15.3. Statistical Analysis: A two-sample t-test will be used with a significance 
level of 0.05 for pain measurements recorded at 6, 24, 72, and 168 hours. A 
linear mixed effects model will be used to compare the groups across time. 
Also, descriptive statistics will be used for patient demographics and 
characteristics. 
15.4. Quality control of the collected data will be overseen by the principal 
investigator. 
16.
Confidentiality 
16.1. Data Security:  
• Data access will be limited to the principal and additional investigators. 
Data will be de-identified including names, geographic subdivisions, all 
elements of dates (except the year), telephone numbers, fax numbers, 
electronic mail addresses, social security numbers, medical record 
numbers, health plan beneficiary numbers, account numbers, certificate/
license numbers, and any other unique identifying number, characteristic, 
or code. Data will be secured on password protected computer consoles 
and AHC-IS servers and an AHC-IS supported desktop computer. 
• AHC-IS Supported Desktop Device #: 20130133 
17.
Provisions to Monitor the Data to Ensure the Safety of 
Participants 
Although the procedures included within this study is of minimal risk, the 
program director/ principal investigator will monitor the data integrity and safety 
of the participants. The principal investigator will ensure that study is conducted, 
recorded, and reported in accordance with the protocol, standard operating 
procedures, and applicable regulatory requirements. 
17.1. Data Integrity Monitoring. 
 
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•
Because the procedures included within this study are of minimal risk, 
the program director/ principal investigator will monitor the data 
integrity, study design, study milestones and study endpoints and 
outcomes.  
•
The principal investigator will ensure that study is conducted, 
recorded, and reported in accordance with the protocol, standard 
operating procedures, and applicable regulatory requirements. 
17.2. Data Safety Monitoring.  
•
Oversight of the trial is provided by the Principal Investigator, Dr. 
Ronald Ordinola-Zapata. Confidentiality throughout the trial will be 
maintained by the Graduate Endodontics residents.  
•
A cumulative review of data will be conducted monthly throughout the 
entirety of the study and data collection. During the review safety data, 
efficacy data, data accuracy and untoward events will be discussed.  
•
Safety information will be collected with case report forms and via 
monthly in-person meetings with the principal investigator. 
•
Dr. Ronald Ordinola-Zapata, the principal investigator and Dr. Jeffrey 
Heyse will monitor the data.  
•
The only condition that should warrant immediate suspension of the 
study is if the department Gentlewave machine stops functioning 
properly and is in need of service.  
18.
Provisions to Protect the Privacy Interests of Participants 
18.1. Protecting Privacy: Participant privacy will be protected by removing any 
identifiable information from the research data 
18.2. Access to Participants: The research team is permitted to access private 
information about participants if they are patients of record at the University 
of Minnesota School of Dentistry. This information may be needed to 
determine if any treatment or medication precautions need to be followed to 
safely treat the participant.  
19.
Compensation for Research-Related Injury 
19.1. Compensation for Research-Related Injury: Compensation for Research-
Related Injury: In the event that this research activity results in an injury, 
treatment will be available, including first aid, emergency treatment and 
follow-up care as needed. Care for such injuries will be billed in the 
ordinary manner to you or your insurance company. If you think that you 
have suffered a research related injury, let the study doctors know right 
away. 
 
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20.
Consent Process 
20.1. Consent Process (when consent will be obtained): 
•
Consent will take place during the consultation appointment, after the 
research participation offer has been extended. 
•
If the potential participant needs time to consider the research 
invitation, a time period of half the time until their treatment initiation 
appointment will be given for the participant to consider the offer. This 
time frame allows the participant to make an informed decision and 
allows the clinic staff time to schedule and plan treatment with the 
Gentlewave system should it be necessary.  
•
It will be the duty of the treating clinician to make sure the participant 
understands the information provided. 
20.2. Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A 
20.3. Non-English speaking Participants: 
•
The University of Minnesota School of Dentistry Graduate 
Endodontics clinic sees a diverse population of patients whom speak 
a variety of languages other than English. Oral information will be 
provided through the use of an interpreter, and written information 
will be provided once it is determined which specific language 
translations are needed.  
•
Interpreters are required by the University of Minnesota to be present 
for any patient interaction for patients who do not speak English. If a 
patient qualifies for recruitment, the interpreter will be available at 
the time of consult and recruitment to present the research 
opportunity and obtain consent. HRP-507 Short form for consent will 
be used. The interpreter is also required to be present during any 
treatment and follow-up visits as well. 
20.4. Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): 
•
Only adults ages 18 years or older will be recruited for research 
participation 
20.5. Adults Unable to Consent: 
•
Adults unable to consent will not be recruited for the study.  
21.
Setting 
21.1. The site of the research will be the University of Minnesota School of 
Dentistry Graduate Endodontics clinic. Research procedures will be 
 
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performed by resident dentists who will be overseen by certified 
endodontists on faculty at the school of dentistry.  
21.2. International Research: N/A 
22.
Multi-Site Research 
N/A 
23.
Resources Available 
23.1. Resources Available:  
•
The study will be conducted by a student investigator and co-residents, 
the faculty advisor will be available for assistance should there be any 
needed. There are also faculty clinicians trained on the usage of the 
Gentlewave device should any issues arise.  
•
Patient consultations for treatment occur daily, either through normal 
treatment scheduling, or through emergency scheduling. These patient 
pools should contain more than a sufficient number of necessary 
participants.  
•
The research treatment, data collection, and data analysis should 
require no more than 12-15 months. 
•
The facilities include 9 dental operatories and a surgical suite equipped 
with all necessary equipment and instruments to perform standard root 
canal treatment, including dental operating microscopes. There is one 
Gentlewave machine, with necessary treatment fluids and hand pieces 
for all research patient cases. 
•
Should participants have a medical emergency, we have a first aid kit, 
ambu bag, oxygen, and AED available. As well as a nearby hospital 
and fast access to emergency responders.  
•
All Graduate endodontics faculty, residents, and assistants have been 
trained on how to properly operate and troubleshoot the Gentlewave 
device. Prior to starting the research, each participating resident will 
be given verbal and written instruction on the consent process, the 
protocol for conducting treatment, and which information needs to be 
collected from each participant. 
24.
References 
•
Schilder H. Cleaning and shaping the root canal. Dent Clin North AM 1974; 18: 
269-96 
•
Peters OA, Peters CI, Basrani B. Cleaning and shaping the root canal system. In: 
Hargreaves KM, Berman LH, EDS. Cohen’s pathway of the pulp. 11th ed. St. 
Louis: Mosby, Inc. 2016: 209-279 
•
Siqueira JF. Microbial causes of endodontic flare-ups. Int Endod J 2003; 36: 
453-63 
 
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•
Gotler M, Bar-Gil B, Ashkenazi M. Postoperative pain after root canal treatment: 
A prospective cohort study; Int J of Dent, vol. 2012, 310467 
•
Haapasalo M, Shen Y, Wang Z, Gao Y. Irrigation in endodontics. British Dental 
Journal 2014; 216: 299-303 
•
Dunter J, Mines P, Anderson A. Irrigation trends among American association of 
endodontists members: A web-based survey. Journal of Endodontics 2012; 19: 
180-2 
•
Hulsmann M, Rodig T, Nordemeyer S. Complications during root canal irrigation. 
Endod Topics; 16: 27-63 
•
Pontes F, Pontes H, Adachi P, Radini C, Ameida D, Pinto D. Gingival and bone 
necrosis caused by accidental sodium hypochlorite injection instead of anesthetic 
solution. Int Endod J 2008; 41: 267-70 
•
Sonendo. The Gentlewave system procedure guide. 2017 
•
Mattscheck DJ, Law AS, Noblett WC. Retreatment versus initial root canal 
treatment: Factors affecting posttreatment pain. Oral Surg Oral Med Oral Pathol 
2001; 92: 321-4 
•
Menhenick KA, Gutmann JL, Regan JD, Taylor SE, Buschang PH. The efficacy 
of pain control following nonsurgical root canal treatment using ibuprofen or a 
combination of ibuprofen and acetaminophen in a randomized, double-blind, 
placebo-controlled study. Int Endod J 2004; 37(8): 531-41 
•
Sigurdsson A, Garland RW, Le KT, Rassoulian SA. Healing of periapical lesions 
after endodontic treatment with the gentlewave procedure: a prospective 
multicenter clinical study. J Endod 2018; 44:510-517. 
 
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