Nanodiamond Modified Gutta Percha (NDGP) Composite for Non-surgical Root Canal Therapy (RCT) Filler Material Applied by Vertical Condensation Obturation Procedure
Phase: NA
Conditions: Dental Pulp Diseases, Dental Pulp Necrosis, Nerve Root Pain Nec
Sponsor: University of California, Los Angeles

 
 
 
 
 
Nanodiamond Modified Gutta Percha (NDGP) Composite for 
Non-surgical Root Canal Therapy (RCT) Filler Material 
 
 
 
 
 
 
 
NCT02698163 
 
 
Study Protocol in Submitted UCLA IRB#15-002015 (March 4th, 2020) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Summary: 
 
Non-surgical root canal therapy (RCT) represents a standard of treatment that 
addresses infected pulp tissue in teeth and protects against future infection while 
preserving the tooth for the patient. RCT involves removing dental pulp comprising 
blood vessels and nerve tissue, followed by the placement of filler material to occupy 
the naturally occurring space where the pulp was removed. Currently, standard of care 
treatment for RCT utilizes gutta-percha (GP) as the root canal filling material. Tooth 
extraction is necessary if the RCT fails or if the tooth fractures. The need for extraction 
after failed RCT might be reduced by increasing the strength of the canal filling material 
closer to that of dentin. Nanodiamonds (NDs) may offer unique advantages due to their 
favorable properties, particularly for dental applications. In this prospective pilot study, 
we will utilize gutta-percha modified with nanodiamonds 5 wt % (NDGP) as the root 
canal filling material. Our research group has previously demonstrated NDGP’s 
improvement in tensile strength compared to those of gutta-percha. We hypothesize 
that NDGP will not have a negative effect on clinical outcome for the patient compared 
to the GP. Additional potential positive benefits include decrease in void space and 
better clinician handling of NDGP during the canal filling procedure. NDGP with its 
increased mechanical properties, potential decrease in void space between the NDGP 
and the tooth's root, and the ease of handling by clinician of NDGP during vertical 
obturation procedure may result in a decrease in the pain experienced by the NDGP 
patients compared to those experienced by the control (GP) patients. Patients will be 
recruited and randomized into two RCT filler material patient groups for this study: 15 
patients for the control, 15 patients with NDGP. For all the patients into the control arm 
of the study, the root canals will be filled with GP at the bottom third up to and including 
the top third, using a standard procedure involving vertical condensation obturation. For 
all the patients into the treatment arm of the study, the root canals will be filled with GP 
at the bottom third, NDGP in the middle third, and again with GP at the top third, using 
the vertical condensation obturation technique. The tooth will be restored with a crown 
for posterior teeth, or a composite filling for anterior teeth. There will ideally be a total of 
four visits: consultation appointment (~1 hour), RCT appointment (~2-3 hours), 6 month 
follow-up appointment (~1 hour), and 1 year follow-up appointment (~1 hour). Additional 
follow-up appointments (~1 hour) prior to the 6 month and 1 year follow-up 
appointments may be required in the event of infection or persistent pain of the root 
canal. Patient data will be categorized by age, weight, gender, and use of other drugs 
which may alter the pain assessment and pilot study success indicators. This study 
investigates a new type of filler, gutta-percha modified by the addition nanodiamond 
material (NDGP), which may be stronger and prevent complications of RCT such as 
tooth fracture to improve treatment outcomes. 
 
Study Protocol: 
Dr. Kang will recruit the patient for this study after the patient’s referral to the 
UCLA endodontics department for root canal therapy. Informed consent will be obtained 
by Dr. Kang from all the patients that will be able to be taken home for patients to 
consider being part of this pilot study. We will stress to the patient that there will be an 
intended benefit and that we will be providing an incentive for joining this study (parking 
vouchers).  The sample population will be screened and collected Dr. Mo Kang, M.S., 

Ph.D., D.D.S. All of the patients must be over 18 years of age when the treatment 
commences. Teeth will be excluded from this study if they had preoperative periodontal 
disease, prior non-surgical and surgical endodontic treatment, or if the apex/apices 
under investigation is/are not discernible in any of the periapical radiographs. The teeth 
that will be excluded from the analysis of the ‘periapical status following treatment’ are 
if: (1) they were not followed-up for at least 6 months, (2) if they were extracted for 
reasons not related to endodontic problems (for e.g. periodontal disease), (3) 
information on the periapical status during the time of extraction was not available. 
Patients will be excluded if they are currently taking medications used to treat 
osteoporosis or currently taking any form of IV bisphosphonates, allergic to dental 
materials, have dental phobia, have MD consult/medically compromised/prophylaxis 
needed, 
have 
any 
developmental/congenital 
disorders, 
have 
mentally 
unstable/psychological issues, have any craniofacial disorder/syndromic cases or have 
a low pain tolerance/inquire about past dental experience. Patients will be also excluded 
if they had any of the following periodontal complications: current moderate to severe 
periodontitis (history is ok), greater than 4mm pocket depths, mobility of the tooth, 
furcation involvement, less than 4 month recall status, periodontal surgery needed and 
poor periodontal diagnosis around tooth of concern (ie. tooth may need to be extracted). 
Patients will also be excluded if they had any of the following restorative complications: 
tooth is non-restorable, has severe abfraction, has severe attrition, severe bruxism or 
history of severe bruxism and insufficient tooth structure (ie. post is needed). Patients 
will be excluded if they have any of the following endodontic complications: endodontic 
treatment needed on third molars, open apices, complicated root canal anatomy 
including sharp curvature, C-shaped canal, pulp stones/calcification, previous 
RCT/initiated pulp therapy, previous apical surgery, lateral lesion, root fracture, severe 
crown fracture (requiring post), perforations, non-endodontic related pathology, 
periapical radiolucency (minimum size to be determined by Dr. Kang), external/internal 
root resorption and surgical root canal procedure. Patients will be excluded if they have 
poor oral hygiene, diet, history or current drug use, and complicated dental history. 
The main operator will be Dr. Zhangrui Liang, DDS. He is a Resident in the 
Section of Endodontics. Eric C. Sung, D.D.S. will be an advisor to the study. He is a 
Professor of Clinical Dentistry and Chair of the Section of Special Patient Care and is 
the Vice Chair of the Division of Advanced Prosthodontics. Dr. Sung is the Program 
Director of the General Practice Residency Program at UCLA. He also received his 
undergraduate at UC Berkeley, and he received his dental and GPR degrees from 
UCLA. 
Primary root canal treatment will be provided to teeth that did not have prior non-
surgical and surgical endodontic treatment. Standard principles of primary RCT 
consistent with the American Dental Association Guidelines will be followed, and the 
treatment protocol will be consistent with UCLA Department of Endodontics treatment 
protocol. All treatments will be performed under both local anesthesia and rubber dam 
isolation to ensure absence of saliva leakage. Sodium hypochlorite solution will be used 
as an irrigant during the whole procedure. The location of the apical terminus will be 
aided by an electronic apex locator. The initial working length will be determined by 
taking a radiograph with the diagnostic file placed at the maximal extent achievable with 
the smallest file. The initial size of the file (recorded as Initial Apical File (IAF)) will be 

the largest that could reach the radiographic apex without force to ensure good 
electrical contact and stability when taking the radiograph. The apical instrumentation 
will be determined by the operator as a distance equal or slightly shorter (<0.5mm) than 
the working length. 
The operator, Dr. Zhangrui Liang, DDS will be choosing his own various types of 
instruments and techniques for canal negotiation and shaping. The instruments 
available for use include: (i) K-flex files (Dentsply Maillefer, Ballaigues, Switzerland), (ii) 
Flex-O-files (Dentsply Maillefer), (iii) Hedström files (Dentsply Maillefer), (iv) GT hand 
instruments (Dentsply Maillefer), (v) ProTaper hand instruments (Dentsply Maillefer), 
(vi) rotary GT instrument system (Dentsply Maillefer), (vii) rotary ProFile instrument 
system (Dentsply Maillefer), (viii) rotary ProTaper instrument system (Dentsply 
Maillefer) and (ix) rotary K3 instrument system (SybronEndo). The stainless steel 
instruments will be used in push-pull filing (Abou-Rass et al. 1980), stem-winding 
(Backman et al. 1992) or balanced-force (Roane et al. 1985) motions. Patency will be 
maintained during canal shaping and filing by placing a small file of size 8 or 10 
passively to 0.5 mm beyond the apex, between each instrumentation step during the 
canal enlargement. The recommended minimum or optimal apical size of canal 
preparation is a size 30 with a taper of 0.06. 
        5.25% Sodium hypochlorite (NaOCl) solution will be the standard root canal 
irrigant. Root canal preparation cream (Premier, Plymouth Meeting, PA, USA) will be 
used as an intracanal lubricant if needed. Calcium hydroxide (Ca(OH)2) will be the 
standard interappointment medicament for teeth with acute pulpitis if removal of pulp 
tissues at the first visit was incomplete. 
 
Patients will be randomized according to a predetermined order created by Dong 
Keun and Theodore Kee via Matlab. 30 patients will be assigned a number 1-30 
according to the order of recruitment for this study 1 being assigned to the first patient 
recruited and 30 to the last patient recruited for this study. The randperm(30,15) 
function will be used to create a list of 15 numbers from the 30 (recruitment order 
number). This list of 15 numbers (recruitment order numbers) will be the Nanodiamond 
gutta percha (NDGP) group to receive the NDGP filler material. The remaining 15 
numbers will be given the standard of care gutta-percha filler material. This list will be 
arranged accordingly for the clinicians’ reference. 
        For all the patients into the control arm of the study, the root canals will be filled 
with gutta percha at the apical third up to and including the coronal third, using the 
vertical condensation obturation technique, also known as the modified Schilder’s warm 
vertical compaction technique (Van Zyl et al. 2005). The root canal sealer used will be 
zinc oxide-eugenol (Kerr Corporation, Orange, CA, USA). After the root canal treatment 
is done, the patient will be treated by Dr. Eric Sung, a general dentist for the restorative 
aspect of the procedure. Depending on how much tooth structure is left, he will decide 
which kind of build-up material to use and if a post is needed. The tooth will be restored 
with a crown for posterior teeth, or a composite filling for anterior teeth. 
For all the patients into the treatment arm of the study, the root canals will be 
filled with gutta percha at the apical third, Nanodiamond gutta percha (NDGP) in the 
middle third, and again with gutta percha at the coronal third, using the vertical 
condensation obturation technique, also known as the modified Schilder’s warm vertical 
compaction technique (Van Zyl et al. 2005). The root canal sealer used will be zinc 

oxide-eugenol (Kerr Corporation, Orange, CA, USA). After the root canal treatment is 
done, the patient will be treated by Dr. Eric Sung, a general dentist for the restorative 
aspect of the procedure. Depending on how much tooth structure is left, he will decide 
which kind of build-up material to use and if a post is needed. The tooth will be restored 
with a crown for posterior teeth, or a composite filling for anterior teeth.     
The goal is to follow-up all treated teeth 6 months and 1 year post-RCT. 
Appointment letters will be mailed to the patients 1 month prior to the follow-up dates. 
Patients, who failed to attend for recall, will be contacted with a personal courtesy call 
by the study team member (dentist on study team) and a more detailed explanation 
letter will be mailed to encourage them to attend follow-up appointments. If patients 
continue to not attend for recall, then the reasons provided by each patient (if provided) 
will be recorded. Recall appointments can be made as necessary other than the 6-
month and 1-year follow-up appointments. Recall appointments will have their own 
specific form detailing the patient’s reason and required procedure. Possible 
complications will be communicated to the patient prior to the study and will be dealt 
with on a case by case basis.  
Follow-up examination consists of updating the general and endodontic history of 
the treated teeth upon clinical and radiographic examination. All patients will be 
interviewed and examined by one individual from the study team to remain consistent 
and reduce sources of bias from involving multiple individuals. Extraoral examination 
will be performed, which includes palpation of masticatory, neck and shoulder muscles, 
lymph nodes, and palpation of the temporomandibular joint for tenderness or any 
abnormalities. Clinical examination of the treated teeth will be carefully noted in detail, 
including the following details: (1) tenderness to percussion of the tooth, (2) tenderness 
to palpation of adjacent soft tissues, (3) presence of sinus tract or abscess, (4) 
periodontal probing depths around the tooth, (5) type/presence of coronal seal and 
restoration. Further examination of the restoration will be done and classified into the 
following three categories: (A) visual or tactile exposure of root filling material, (B) 
clinical or radiographically detected marginal discrepancy but without visual or tactile 
exposure of root filling to the oral cavity, (C) satisfactory coronal restoration with good 
retention and margins. 
The radiographs will be taken digitally with size 1 or 2 XDR Digital Intraoral 
sensors (XDR Radiology, Los Angeles, CA, USA). The images will then be transmitted 
and analyzed by the XDR program. 
        If the patient feels persistent discomfort from the treated tooth at follow-up, 
periapical radiographs at different horizontal angles will be taken to detect any 
radiolucent pathology that may be superimposed upon the root. If the patient is 
pregnant at the time of the follow-up appointment, the radiographic examination will be 
deferred until after delivery. 
All the preoperative, immediate post-obturation, and follow-up radiographs will be 
viewed on the computer screen with the “caries” and “endo” detection feature and 
magnifying viewer tools in the XDR program as needed. The preoperative periapical 
status of each root will be classified into three categories: (1) intact periodontal 
ligament, (2) widened periodontal ligament or (3) periapical lesion. The diameter of the 
lesion preoperatively and at follow-up was measured using the measuring ruler tool in 
the XDR program. The diameter for widened periodontal ligament will be recorded as 

0.5 mm. The quality of previous treatment will be judged satisfactory if a well-condensed 
root filling extends to within 2 mm of the radiographic root apex. 
Treatment success will be evaluated based on two outcome measurements: (1) 
absence of apical periodontitis via clinical and radiographic evaluation, (2) tooth 
survival. 
The assessment of treatment success will strictly be defined as absence of pain, clinical 
signs of inflammation or swelling, and radiographic measures of complete healing (i.e. 
presence of normal periodontal ligament space, intact lamina dura, etc). A potential 
consideration for treatment success will also include aspects from the patient such as 
the absence of pain and/or clinical signs of inflammation or swelling and radiographic 
measures of complete healing or incomplete healing (i.e. reduced size of periapical 
lesion without normal periodontal ligament space width).  
In some of these cases where the failure is not due to an iatrogenic perforation, a 
secondary RCT, also called non-surgical endodontic retreatment, might be indicated to 
resolve any pulp tissue that may have been left behind. A secondary RCT may also be 
necessary if there is failure of primary RCT due to narrow or curved canals were not 
treated during the initial procedure, complicated canal anatomy went undetected in the 
first procedure, placement of the crown or other restoration was delayed following the 
endodontic treatment, inadequate seal during primary RCT and a radiolucency that still 
persists or expands. Furthermore, a secondary RCT is indicated if any infection from 
primary RCT causing persistent pain and or periapical lesion seen in the radiograph. 
This secondary RCT will still be done with NDGP in the middle third of the root, as the 
cause of failure in the first place would have been because of regular in-tact gutta 
percha extruding from the apex or insufficient instrumentation.  
The root canal therapy (RCT) procedure has potential risks and complications 
associated with the procedure: possible pain swelling, separation of instrument, 
perforation, fracture/crack, requirement for permanent restoration, and extraction of 
tooth if persistent infection is observed. If the tooth is indicated for an extraction instead, 
the extracted tooth will be evaluated for other potential causes of failure (eg. cracked 
tooth, missed extra canals, difficult canal anatomy, etc.). Extractions should be 
considered upon the identification of a fractured and cracked tooth during an 
apicoectomy. After the root canal therapy, if pain or pressure persists for more than a 
few days after the RCT, the endodontist would need to evaluate the prognosis of the 
tooth and determine whether the tooth is viable or needs extraction due to inadequate 
infection control of the canal or damage to tooth structure during the RCT. An extraction 
may also be indicated several years after the RCT due to persistent infectious bacteria 
or microleakage of the endodontically treated tooth. Other indications for extractions 
include perforations, coronal breakdown, or periodontal disease. If a tooth were to be 
extracted due to endodontic problems, such as persistent pain, swelling, sinus or 
periapical lesion, the treatment will be considered as a failed outcome. Tooth extraction 
without any information on postoperative periapical status will be excluded from 
analysis.  We have to keep in mind that even conventional RCTs do not have a 100% 
success rate. Most studies say that primary RCTs have about a 86% success rate - so 
when taking that into consideration, we cannot assume that if the procedure fails, it is 
due to the NDGP material.         

Customized forms, recorded by endodontic postgraduate students, will be used 
for recording follow-up information and radiographic assessments. The patient’s medical 
conditions will be self-reported onto a standard medical history form at the first 
appointment and will be verified and updated by interview prior to the both arms of 
control and treatment and at the follow-up appointment. While all conditions reported by 
the patient will be recorded, only those that will be common among the patients or 
previously reported to have significant association with treatment outcome will be further 
analyzed. 
        Relevant demographic data, medical history, preoperative pain history, 
diagnostic and treatment details of the tooth were recorded on collection forms and then 
entered electronically into a database (Microsoft Office Access software). Handling of 
patients’ personal data will accordingly conform to the Data Protection Act 1998. All 
data will be made anonymous on the database. 
Nanodiamonds (5 nm) will be purchased from the NanoCarbon Research 
Institute Co., Ltd. (Nagano, Japan) prepared as a 50 mg/mL aqueous ND stock solution. 
Unmodified gutta-percha points will be purchased from SybronEndo (Glendora, CA, 
USA). 
Dean Ho's lab personnel (Dong-Keun Lee and Theodore Kee) will prepare the 
NDGP. First, the nanodiamond (ND) stock solution will be sterilized. The ND stock 
solution will then be mixed with ethanol. In a separate beaker, the unmodified gutta-
percha tips will be dissolved in eucalyptol. Next, the previously prepared ND solution will 
be mixed with the eucalyptol solution containing the dispersed gutta-percha. This final 
solution will then be sonicated for 5-15 min to mix the ND with the gutta-percha in the 
solution. Next, the solution will be lyophilized overnight to get rid of all the solvents in 
the solution. After lyophilization, solid NDGP composite filler material will be heated at 
70-90C allowing the NDGP to be manually rolled into the cylinder shape of the standard 
of care gutta-percha filler material used in non-surgical RCT vertical condensation 
obturation. 
 
Statistical Analysis: 
 
For the analysis of the elastic moduli, tensile strength, and percentage of elongation 
properties of the NDGP, a two-tailed Student’s t test was used. α was set at 0.05, and P 
values <0.05 were considered statistically significant. All tests were performed in 
triplicate, and statistical analyses were conducted using MATLAB R2014a (MathWorks 
Inc.).