Platelet-rich Fibrin With Minocycline Versus Arestin in Non-surgical Periodontal Therapy: A Split-Mouth Randomized Controlled Clinical Trial
Phase: NA
Conditions: Non-surgical Periodontal Therapy
Sponsor: Center for Advanced Rejuvenation and Esthetics

Official Title: Platelet-rich Fibrin With Minocycline Versus Arestin in Non-surgical Periodontal 
Therapy: A Split-Mouth Randomized Controlled Clinical Trial 
Unique Protocol ID: 12625-NEstrin 
Date of Document: 2/21/2026 
Principal Investigator: Dr. Nathan Estrin 
Brief Title: PRF + Minocycline vs Arestin in Non-surgical Perio Therapy 
Secondary IDs: None 
 
 
Abstract  
Periodontitis is a multifactorial disease drive by a dysbiotic microbiome.1 In a recent 
publication, the American Academy of Periodontology and the European Federation of 
Periodontology introduced a new multidimensional classification of periodontal and peri-implant 
diseases and conditions, segmenting periodontitis by stages (I-IV) based on disease severity and 
management complexity, and grades (A-C) based on risk of progression and treatment response.1 
Non-surgical treatment remains the foundational, first line of defense with scaling and root 
planing, however several adjunctive therapies have shown promise in enhancing outcomes. 
These include platelet-rich fibrin (PRF), 2 and local antibiotics such as minocycline.3 
 
Objective  
This project aims to investigate and compare PRF with minocycline compared to Arestin when 
utilized as adjunctive therapies in the non-surgical management of Stage II or Stage III and 
Grade A or B periodontitis. 
 
Project Design  
This research will be a 6-month randomized trial involving a patient population diagnosed with 
Stage II or III periodontitis. The treatment groups and modalities will all randomly assigned to 
different sites within the same individual. Thus, the subject serves as their own control and not 
assigned to one specific group.  
 
 
Background Information and Scientific Rationale  
Periodontitis is a multifactorial disease caused by a dysbiotic microbiome.1 In a recent 
publication, an organizing committee of the American Academy of Periodontology and the 
European Federation of Periodontology reported a consensus of a new classification of 
periodontal and peri-implant diseases and conditions.1 The 2017 workshop resulted in a new 
classification of periodontitis characterized in a multidimensional staging and grading system. 
The Stages, based on the severity and complexity of management were defined as Stage I: Initial 
periodontitis; Stage II: moderate periodontitis; Stage III: Severe periodontitis with potential for 
additional tooth loss; Stage IV: Severe Periodontitis with potential for loss of dentition.1 The 
grades were based on the evidence of risk of rapid progression and anticipated treatment 
response. Grade A: slow rate of progression, Grade B: moderate rate of progression, Grade C: 
rapid rate of progression.1 
There are many different treatment modalities in assessing periodontal disease. 
Conventionally, the first phase of treatment includes non-surgical therapy with ultrasonic scalers 
and hand instruments. However, evidence is accumulating to support many adjunctive treatment 

modalities to non-surgical therapy. These treatment modalities include the use of growth factors 
such as platelet rich fibrin (PRF)2, as well as local antibiotics3. 
Platelet rich fibrin is a fibrin matrix in which platelet cytokines, growth factors, and cells 
are trapped in a fibrin clot and utilized in various medical and dental specialties including 
periodontics, dermatology, and orthopedics.4 Having been discovered in 1974, platelet 
concentrates are on the forefront of regenerative medicine, and have recently shown impressive 
results in regenerating the periodontal supporting structures.2, 4 Given that the platelets are 
derived from the patient’s own blood draw, there are very little risks involved in using this 
treatment. However, possible risks with PRF including common risks associated with a normal 
blood draw including pain, bleeding, fainting, bruising, and hematoma. To minimize these risks, 
all blood draws in this study will be completed be a qualified member of the research team. 
 
Participant Selection  
 
Participants will receive comprehensive information regarding the treatment procedure, materials 
utilized, and potential risks or complications to ensure full understanding. This research will 
encompass a comprehensive and inclusive patient selection process to ensure a diverse and 
representative sample. Eligible participants will be adults aged 18-65 with diagnosed Stage II or 
III Periodontal Disease. Efforts will be made to include individuals from various racial, ethnic, and 
socioeconomic backgrounds, as well as different genders. Exclusion criteria will be carefully 
defined to maintain the study's integrity while prioritizing inclusivity. If the subject decides to 
participate in the study, subjects will be given ample time to review the consent form and ask any 
questions before signing. Subjects will be given a copy of the informed consent for their reference. 
Participation in the study is entirely voluntary and they can withdraw at any time without penalty.  
Women with the potential for childbearing will be asked to complete a pregnancy test during the 
screening process. Throughout the study, it is a requirement for female participants to use an 
approved method of birth control. Acceptable methods include abstinence, oral contraceptives, 
contraceptive injections, intrauterine devices, double barrier methods, contraceptive patches, or 
male partner sterilization. Importantly, women with childbearing potential will not face exclusion 
from participation in the study.  
 
Inclusion Criteria  
• Male and Female subjects age 18-85 with Stage II or III Periodontitis according to the 2017 
periodontal classification. 
• Validation of diagnosis through periodontal charting and necessary radiographs 
 
Exclusion Criteria  
• Previously treated periodontal disease (within the last 6 months) 
• Stage I or Stage IV Periodontitis 
• Patients with a plaque score greater than 30% 
• Radiation or immunosuppressive therapy 
• Neurologic disease or disorder  
• Major mechanical obstruction to the mouth opening  
• Acute capsulitis  
• Bone metabolic disease 
• Current systemic antibiotic treatment or within 3 months prior to the study 
• Drug addiction or alcohol abuse 

• Pregnancy, planning to become pregnant and or nursing  
• Type 2 uncontrolled diabetics 
 
Enrollment  
This multi-site study is expected to enroll a total of up to 20 subjects. 
 
Site Recruitment  
A periodontist practicing at Lakewood Ranch dental will be the target site of the study.  
 
Data Analysis and Interpretation  
All collected data, including personal and medical information, is handled with the highest level 
of security and confidentiality to uphold the privacy and rights of the participant. The informed 
consent process, a key component of the protocol, clearly communicates to participants how their 
data will be treated, emphasizing the commitment to confidentiality. Data collection, storage, and 
transmission procedures incorporate high-security measures, including encryption and password 
protection, to prevent unauthorized access. Personally identifiable information is carefully 
managed, with a focus on anonymization or de-identification wherever possible to minimize the 
risk of participant identification. The research team is granted access only on a need-to-know basis, 
and strict access controls are implemented. Regular monitoring, audits, and compliance checks are 
conducted to ensure that data confidentiality measures are consistently followed throughout the 
study, promoting trust among participants and maintaining the integrity of the study. Safeguarding 
data confidentiality is of utmost importance to uphold the privacy and rights of study participants.  
This study will undertake a comprehensive analysis to compare outcomes across distinct treatment 
groups. The primary focus will involve the improvement in periodontal parameters within these 
groups on the same subject. Additionally, a meticulous assessment of the safety profile associated 
with the treatment groups will be conducted, considering any reported adverse events. The goal is 
to draw conclusive findings including the efficacy and safety of the varying treatment groups in 
treating periodontal disease. 
 
Compensation to Participants  
Participants will not receive any type of compensation or payment for their participation in the 
study.  
 
Financial Responsibility  
In our commitment to making research accessible and inclusive, there will be no cost associated 
with participation in this study. This means that there will be no fees, charges, or expenses incurred 
by participants throughout the study. Our goal is to ensure that everyone interested in contributing 
to the advancement of knowledge can do so without financial constraints. Participation is not only 
crucial to the success of our research but also contributes to creating a more equitable and 
accessible research environment for all.  
In the case of an adverse event (AE) or severe adverse event (SAE) directly associated with the 
study, participants will not be financially responsible for any consequences resulting from their 
participation in the study. Should a serious AE occur, any associated medical expenses or required 
interventions will be covered by the research team. We are fully committed to providing support 
and resources to manage and address any unexpected challenges that may arise, reaffirming our 
commitment to the ethical and responsible conduct of research.  

 
Adverse Event Reporting  
Adverse event reporting aims to ensure participant safety, facilitate the evaluation of the 
intervention's safety profile, and contribute to the overall understanding of potential risks 
associated with the treatment groups and non-surgical treatment of periodontal disease. When an 
adverse event (AE) or severe adverse event (SAE) occurs, it will be promptly and accurately 
documented. The AE or SAE will be classified in nature, severity and relation to laser therapy and 
the other adjunctive applications. It will be reported to all parties including the regulatory authority 
and ethics committee. The subject will be closely followed until the AE or SAE has been resolved. 
Timely and transparent reporting is essential for maintaining the integrity of the study, protecting 
participant welfare, and informing regulatory decisions to ensure the ongoing safety and efficacy 
of medical interventions. 
 
Principle Investigator Safety Monitoring  
 
1.) Adverse Event Monitoring:  
a. Evaluation of any adverse events (AEs) or serious adverse events (SAEs), 
which are unfavorable or unintended medical occurrences, to determine their 
nature, severity, and relationship to the intervention.  
 
2.) Data Collection and Analysis:  
a. Continuous collection and analysis of safety-related data including 
participant health status and reported symptoms, to identify any patterns or 
trends that may indicate safety concerns.  
b. Data collection will take place at the second maintenance visit (6 months after 
the non-surgical therapy and will mark conclusion of study) 
 
3.) Regular Assessments:  
a. Assessment will be conducted at each visit to monitor for potential side 
effects, complications, or changes in health status related to the intervention.  
b. Each maintenance visit will include a supragingival cleaning.  
 
4.) Compliance with Protocols:  
a. All treatment protocols will be followed, including adherence to safety 
procedures and guidelines outlined in ethical standards and regulatory 
requirements.  
 
5.) Communication:  
a. Clear communication with the principal investigator, research staff, and 
participants to promptly report and address any safety concerns or adverse 
events.  
 
6.) Ethical Oversight:  

a. Ethical principles and guidelines will be followed to prioritize participant 
safety and ensure that the research is conducted with the highest standards 
of integrity.  
 
7.) Regulatory Reporting:  
a. Reporting and monitoring of any adverse events and safety-related data 
directly to the institutional review boards (IRB) and all related parties.  
 
8.) Risk-Benefit Assessment:  
a. Continued assessment of the overall risk-benefit profile of the intervention to 
determine whether the potential benefits outweigh the risks and whether any 
modifications to the study protocol are necessary.  
 
9.) Documentation:  
a. Through documentation of all safety-related information, including adverse 
events, their resolution, and any actions taken to address safety concerns.  
 
Data Collection  
Ensuring data confidentiality is paramount in a research protocol to protect the privacy of 
participants and maintain the integrity of the study. The protocol outlines rigorous measures to 
safeguard all collected data, including personal, medical, and potentially sensitive information 
related to periodontal disease. Key considerations for data confidentiality in a research protocol 
include: 
 
Informed Consent Process:  
Clearly articulate to participants how their data will be handled, emphasizing the importance of 
confidentiality during the informed consent process. Verbalize the extent to which their 
information will be anonymized or de-identified to protect their identity.  
 
Resources Available  
This study will be facilitated by Dr. Richard Miron and Dr. Nathan Estrin, both are trained in GCP, 
HSR, and HIPPA. Staff is also trained in data collection, documentation, and storage.  
 
Early Withdrawal of Subjects  
Ideally, each participant should stay engaged in the study until the mandated follow-up period 
concludes. Nevertheless, participation in any study is entirely voluntary, and participants retain the 
right to withdraw at any time without facing penalties or loss of benefits. Possible reasons for 
discontinuation may encompass but are not restricted to, the following:  
• 
Unacceptable adverse experience  
• 
The subject is lost to follow-up  
• 
The subject becomes pregnant or wishes to become pregnant  
• 
Subjects withdraw consent for any reason  
• 
Investigators withdraw in the best interest of the subject(s)  
• 
Replacement of Screen Fails and Early Termination  
• 
Study Termination  

For those subjects who discontinue participation early, each subject will be followed for 30 days 
for adverse event monitoring (serious adverse reactions will be monitored for 90 days) after 
discontinuation. Monitoring of adverse reactions may be done by telephone at the study site 
director's discretion. 
 
Interventions  
 
All subjects will undergo scaling and root planing with a cavitron, lasers, and 
conventional curettes at all sites and receive oral hygiene instructions (OHI). After non-surgical 
periodontal therapy, one interproximal site will be assigned to receive PRF + minocycline while 
another interproximal site will receive Arestin as adjunctive therapies. Assignment of the 
treatment groups to the patient’s dentition will be randomly selected by a member of the research 
team.  
 
A detailed breakdown of the treatment groups is listed below: 
 
1) PRF mixed with Minocycline 
2) Arestin 
 
Participants diagnosed with Stage II or III periodontitis who wish to participate in this study. 
These treatment groups and modalities are all completed at different sites within the same 
individual. Thus, the subject serves as their own control and not assigned to one specific group.  
 
Methods  
Once patients are placed in their corresponding group, they will undergo scaling and root planing 
(SRP) to be completed in one visit. After completion of the second scaling and root planing, the 
adjunctive treatment will be performed in the same visit. The patient will return two-weeks post-
operatively to review home care. They will have a supragingival periodontal maintenance 
appointment at 3-months after the SRP visit and again at 6-months. At the 6-month periodontal 
maintenance, periodontal parameters will be recorded. 
 
Therapeutic Material Preparation  
Blood will be collected through an aseptic technique. Using a butterfly needle set and vacutainer 
tubes before centrifuged. Minocycline will be retrieved from Apothecare Pharmacy and a dose of 
2mg will be mixed in with the PRF. 
 
Scaling and Root-Planing Protocol 
Patients will undergo scaling and root planing by a study personnel utilizing a combination of hand 
instruments and ultrasonic device to remove all calculus. An ODU-11/12 explorer will be utilized 
to ensure complete removal of calculus and smooth root surfaces. Left and right sides will be 
completed at the same visit according to standard dental protocols.  
 
Oral Hygiene Visit 
Patients will be re-evaluated 2 weeks after the second scaling and root planing visit to review 
proper oral hygiene and ensure no post-operative complications.   
 
Periodontal Maintenance Treatment 

Patients will be placed on a 3-month periodontal maintenance with data collection occurring at the 
second maintenance (6-months). They will also have supragingival scaling completed with 
curettes and ultrasonic device completed by a trained study personnel. The first maintenance will 
begin 3 months after the scaling and root planing visit until the 6-year conclusion of the study (2 
periodontal maintenance visits).  
 
Study Timeline  
Visit 1 - Screening/Baseline  
• 
Informed Consent  
• 
Medical History  
• 
HIPPA Form  
• 
Urine HCG test if applicable  
• 
Inclusion/Exclusion Criteria  
• 
Periodontal charting 
• 
Fasting blood draw 
 
Visit 2- Treatment  
• 
Treatment (Scaling and Root Planing both sides with adjunctive treatment groups) 
 
Visit 3- 2 week Evaluation  
• 
Review oral hygiene instructions.  
 
Visit 4- Three-month Periodontal maintenance 
• 
Supragingival scaling  
• 
Review oral hygiene instructions 
 
Visit 5- six-month Periodontal maintenance 
• 
Supragingival scaling  
• 
Complete periodontal charting 
 
 
 

Periodontal Examination - Measurements in mm - absent (0) / present (1)  Date:…./…./…. Clinical parameters: Probing Depth (PD), 
Gingival Bleeding (GB), Recession (Rec), Clinical Attachment Loss (CAL), Missing teeth (MT) 
 
Facial Surface of Maxilla 
 
 
PD 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
D B M D B M D B M D B M D B M D F M D F M D F M M F D M F D M F D M B D M B D M B D M B D M B D 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rec 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Palatal Surface of Maxilla 
 
 
PD 
16 
15 
14 
13 
12 
11 
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
D B M D B M D B M D B M D B M D F M D F M D F M M F D M F D M F D M B D M B D M B D M B D M B D 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rec 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Facial Surface of Mandible 
 
 
PD 
32 
31 
30 
29 
28 
27 
26 
25 
24 
23 
22 
21 
20 
19 
18 
17 
D B M D B M D B M D B M D B M D F M D F M D F M M F D M F D M F D M B D M B D M B D M B D M B D 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rec 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lingual Surface of Mandible 
 
 
PD 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
D B M D B M D B M D B M D B M D F M D F M D F M M F D M F D M F D M B D M B D M B D M B D M B D 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rec 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Publication Upon the conclusion of the study, Dr. Richard Miron BMSc, MSc, PhD, DDS will 
author and publish the research. The scientific article aims to enhance the treatment of patients 
with periodontal disease and diabetes.  
 
Conclusion  
The objective of this project is to compare PRF with Minocycline to Arestin for managing 
periodontal disease in individuals with periodontal disease in Stage I and Stage II periodontal 
patients. The results of this research have the potential to advance the therapeutic choice for 
those experiencing active periodontal disease, ultimately enhancing their quality of life.  

 
References 
 
1. 
Papapanou PN, Sanz M, Buduneli N, et al. Periodontitis: Consensus report of 
workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and 
Peri‐Implant Diseases and Conditions. Journal of periodontology 2018;89:S173-
S182. 
2. 
Preeja C, Arun S. Platelet-rich fibrin: Its role in periodontal regeneration. The Saudi 
Journal for Dental Research 2014;5:117-122. 
3. 
Gopinath V, Ramakrishnan T, Emmadi P, Ambalavanan N, Mammen B. Effect of a 
controlled release device containing minocycline microspheres on the treatment of 
chronic periodontitis: A comparative study. Journal of Indian Society of 
Periodontology 2009;13:79. 
4. 
Naik B, Karunakar P, Jayadev M, Marshal VR. Role of Platelet rich fibrin in wound 
healing: A critical review. J Conserv Dent 2013;16:284-293.