Clinical trial NCT03762915
Conditions: SRP Minocycline HCl Microspheres Biomarkers
Sponsor: University of Minnesota
Start date: 2019-05-20; Completion date: 2022-04-01
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary goal of this study is to investigate the qualitative and quantitative effects of scaling and root planing (SRP) with and without minocycline HCL microspheres, 1 mg on periodontal pathogens and overall bacterial load.

A randomized controlled clinical trial of a control (SRP) group and an experimental (SRP with minocycline HCl microspheres, 1 mg) group is planned.

Specific Aim 1: Evaluate the cumulative oral periodontal bacterial burden in both control and test groups over a six month period.

Specific Aim 2: Assess gingival crevicular fluid (GCF) and serum biomarkers of inflammation.

Detailed description:
A randomized controlled clinical trial of a control (SRP) group and an experimental (SRP with minocycline HCl microspheres, 1 mg) group is planned.

The intervention of minocycline HCl microspheres, 1 mg will be administered in the experimental group at baseline and the three month periodontal maintenance visit. Saliva samples, GCF, and blood serum will be collected at four time points (baseline, 1, 3, and 6 month follow up). Saliva will be analyzed for overall pathogen burden. GCF will be analyzed for Interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-α). Serum will be analyzed for C-reactive protein (hsCRP), haptoglobin (Hp), hemoglobin A1c (Hgb A1c), IL-1, IL-6, and TNF-α.

Arms: arm 1: The intervention of minocycline HCl microspheres, 1 mg will be administered in the experimental group at baseline and the three month periodontal maintenance visit. arm 2: The control group will not have minocycline HCl microspheres, 1 mg administered.
Interventions: intervention 1: minocycline HCl microspheres
Intervention descriptions: intervention 1: Minocycline HCl microspheres, 1 mg are approved by the Food and Drug Administration (FDA) as an adjunct to SRP procedures for reduction of pocket depth in patients with adult periodontitis.

Protocol documents:
ICF_005.pdf: 
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Title of Research Study: Effect of Non-Surgical Periodontal Therapy With and Without Minocycline 
HCl Microspheres, 1 mg on Bacterial Load and Systemic Markers of Inflammation 
 
Investigator Team Contact Information: Michelle Arnett, RDH, BS, MS 
For questions about research appointments, the research study, research results, or other 
concerns, call the study team at:  
Investigator Name: Michelle Arnett 
Investigator Departmental Affiliation: School 
of Dentistry, Division of Dental Hygiene  
Phone Number:612-624-3457 
Email Address:marnett@umn.edu 
Study Staff: 
Danna Hickey 
School of Dentistry, Division of Dental 
Hygiene  
Phone Number: 612-626-4744 
Email Address: hicke097@umn.edu 
 
Supported By: This research is supported by Bausch Health Companies, Inc. 
 
 
 
 
 


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Key Information About This Research Study 
 
The purpose of this study is to investigate scaling and root planning (SRP) with and without 
minocycline HCl microspheres, 1 mg for the management of periodontal disease (gum disease) 
and the impact on bacteria in the saliva  and  inflammatory markers in the blood.  
SRP is known as a “deep cleaning” to treat gum disease. Minocycline HCl microspheres, 1 mg is 
an antibiotic. The antibiotic is in a powder form and is placed in a pocket of the gums. The 
antibiotic (minocycline HCl microspheres, 1 mg) is approved by the Food and Drug 
Administration (FDA) as an adjunctive therapy to treat gum disease.  
Participants in this study will be randomized to one of two groups. The group participants are 
placed by chance, like flipping a coin. Neither the participant nor the study members will 
choose what group participants are in. One group will have deep cleaning  and the other will 
have a deep cleaning  with the powder antibiotic placed in the pockets of their gums.  
Both groups will have saliva, fluid samples around teeth, blood collected, and their gums 
measured at four different times. For saliva collection, you will rinse with a solution and spit in 
a tube. The fluid around your teeth will be collected by a paper strip that is placed between 
your gums and your teeth. Neither of the methods of fluid collection are painful. Blood will be 
collected just like a regular blood draw at a doctor’s appointment. The measurement of your 
gums is the same as a dental exam.  
What is research?  
 
Doctors and investigators are committed to your care and safety. There are important differences 
between research and treatment plans: 
 
 
 
 
 
 
 
● The goal of research is to learn new things in order to help groups of people in the future. 
Investigators learn things by following the same plan with a number of participants, so they do 
not usually make changes to the plan for individual research participants. You, as an individual, 
may or may not be helped by volunteering for a research study.   
● The goal of clinical care is to help you get better or to improve your quality of life. Doctors can 
make changes to your clinical care plan as needed. 
 
Research and clinical care are often combined. One purpose of this informed consent document 
is to provide you clear information about the specific research activities of this study.  
 
 
Why am I being asked to take part in this research study? 
We are asking you to take part in this research study because you either need SRP or localized SRP.  
 
 


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What should I know about a research study? 
● Someone will explain this research study to you. 
● Whether or not you take part is up to you. 
● You can choose not to take part. 
● You can agree to take part and later change your mind. 
● Your decision will not be held against you. 
● You can ask all the questions you want before you decide. 
 
Why is this research being done? 
 
The research is being done to compare the changes of bacteria in saliva, bacteria in the fluid around 
teeth, and inflammatory markers in the blood with the treatment of SRP with and without minocycline 
HCl microspheres, 1 mg. 
 
In this study, we want to know if SRP with and without minocycline HCl microspheres, 1 mg will 
decrease bacteria levels in the saliva and in the fluid around the teeth. Collecting saliva and fluid around 
the teeth is a non-invasive way to determine the effectiveness of SRP with and without minocycline HCl 
microspheres, 1 mg. We also want to know if SRP with and without minocycline HCl microspheres, 1 mg  
decreases inflammatory markers in the blood. Minocycline HCl microspheres, 1 mg is Food and Drug 
Administration (FDA) approved to use with SRP and is commonly practiced at a regular dental visit.   
 
Oral health impacts general health. There is evidence that inflammation in the mouth increases 
inflammation in the body. This study may benefit others by providing information on how to manage 
gum disease. In addition, determine early onset and management of chronic inflammatory diseases. 
 
How long will the research last? 
We expect that you will be in this research study for six months. There are four visits total. Visits will 
range from 1-3 hours in time.  
 
What will I need to do to participate? 
You will be asked to participate in four research visits. You will have SRP completed one time with or 
without minocycline HCl microspheres, 1 mg. You will be asked for four saliva and blood samples. The 
fluid around your teeth will be collected and measurements of your gums will be recorded four times as 
well. During two of the four visits, you will also have your teeth cleaned.  
More detailed information about the study procedures can be found under “What happens if I say yes, I 
want to be in this research?” 
Is there any way that being in this study could be bad for me? 
There are no known risks for SRP with or without minocycline HCl microspheres, 1 mg different than 
having this procedure completed at your regular dental visit.  
The collection of saliva, fluid around your teeth, or measurements of your gums is non-invasive and 
similar to a regular dental visit. In addition, having your blood drawn poses no more risk than having 
your blood drawn at a regular medical visit. 


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More detailed information about the risks of this study can be found under “What are the risks of this 
study?  Is there any way being in this study could be bad for me? (Detailed Risks)” 
Will being in this study help me in any way? 
We cannot promise any benefits to you or others from your taking part in this research. However, 
possible benefits include treatment of your gum disease with SRP (with or without minocycline HCl 
microspheres, 1 mg) and two periodontal maintenances (teeth cleanings) over a six month period at no 
cost. After participation of this study, treatment for your gum disease is your responsibility.  
Doctors, researchers, and the public may benefit from this study by having information to manage gum 
disease. In addition, this study may provide information on the identification, onset, and management 
of oral and systemic chronic diseases.     
What happens if I do not want to be in this research? 
Research is completely voluntary and you do not have to participate if you do not want to. Instead of 
being in this research study, your choices may include having your gum disease treated at the University 
of Minnesota (UMN) School of Dentistry (SoD) or your dental home at your own cost.  
 
Detailed Information About This Research Study 
The following is more detailed information about this study in addition to the information listed above. 
How many people will be studied? 
We expect about 60 people will be in this research study.  
 
Who can take part in this study?  
To participate in this study, you must:  
• Be at least 21 years of age 
• Have gum disease and need a deep cleaning 
• Have eight sites with pockets ≥5mm with bleeding on probing (any quadrant) 
 
You cannot participate in this study, if you:  
• Are unable to comply with study protocol 
• Had a deep cleaning within the last 6 months 
• Have smoked cigarettes within the last year 
• Have taken antibiotics ≥2 weeks or taken antibiotics in the last six weeks.  
• Are pregnant, planning to become pregnant, or unsure of pregnancy status (self- reported) and 
mothers who are breastfeeding.  
• Have cardiac (heart) conditions  
• Have any uncontrolled medical condition or immunocompromised that may impact the study 
(uncontrolled diabetes HbA1c > 7, HIV, etc.) 
• Have a tetracycline allergy 
• Are taking any medications that may impact periodontal conditions (Phenytoin, calcium antagonists, 
cyclosporin, warfarin, or NSAIDS) 
 


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What happens if I say “Yes, I want to be in this research”? 
If you decide to take part in the study, you will be randomized to one of two groups. The group you will 
be in is by chance, like flipping a coin. Neither you nor the study members will choose what group you 
are in. One group will have SRP and the other will have SRP with minocycline HCl microspheres, 1 mg.  
All study visits will be in the Oral Health Clinical Research Clinic (OHCRC) at the UMN SoD. Blood draws 
will be collected at the M Health Clinical Research Unit (CRU). You will be escorted there by a study team 
member and can get there by the second floor of the UMN SoD. 
Screening (V0) 
The study details, risks, benefits, and time commitment will be discussed with you. You will have time to 
read the informed consent form (ICF) and have the opportunity to ask a study team member questions. 
If you elect to sign the ICF to participate, we will have a study team member confirm inclusion and 
exclusion criteria before research activities begin. You may proceed to the baseline (BL) visit 
immediately if you elect. This visit will take approximately 1-2 hours. 
 
Enrollment/Baseline (V1) 
Your demographic information including age, gender, ethnicity, and education level will be collected. 
Your medical history will be reviewed and your vitals will be recorded (blood pressure and heart rate). 
Saliva, fluid around your teeth, and measurements of your gums will be collected.  You will be escorted 
to CRU by a study team member to have your blood drawn. After the blood draw, you will have SRP or 
SRP with minocycline HCl microspheres, 1 mg depending on your assigned group. Both groups will have 
a standard of care treatment for gum disease. Minocycline HCl microspheres, 1 mg is Food and Drug 
Administration (FDA) approved to use with SRP and is commonly practiced at a regular dental visit.   This 
visit will take approximately 2.5-3 hours. 
 
1 month follow-up (V2)  
Your medical history will be reviewed and your vitals will be recorded (blood pressure and heart rate). 
Saliva, fluid around your teeth, and measurements of your gums will be collected.  You will be escorted 
to CRU by a study team member to have your blood drawn. At the conclusion of V2 you will get a $50 
gift card.  This visit will take approximately 1-1.5 hours. 
 
3 month follow-up (V3) 
Your medical history will be reviewed and your vitals will be recorded (blood pressure and heart rate). 
Saliva, fluid around your teeth, and measurements of your gums will be collected.  You will be escorted 
to CRU by a study team member to have your blood drawn. After the blood draw, a periodontal 
maintenance (teeth cleaning) will be completed for both groups. The test group will have minocycline 
HCl microspheres, 1 mg placed in the same sites as the BL visit. At the conclusion of V3 you will get a $50 
gift card.   This visit will take approximately 1.5-2 hours 
 
6 month follow-up (V4) 
Research activities will be the same as V2. In addition, both groups will have a periodontal maintenance 
(teeth cleaning). At the conclusion of V4 you will get a $100 gift card for completing ALL research visits. 
You may also elect a portfolio of your oral pathogenic bacteria and inflammatory markers identified 
during the study. These visits will take approximately 1.5-2 hours 


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What are my responsibilities if I take part in this research? 
If you take part in this research, you will be responsible for:  
• 
Complying with the study protocol and research activities 
• 
Attending your research visits that will be scheduled in advance 
• 
Being on time for your research visits 
• 
Giving advance notice if you need to reschedule within your research window for each visit.  
What happens if I say “Yes”, but I change my mind later? 
You can leave the research study at any time and no one will be upset by your decision.   
 
If you decide to leave the research study, contact the investigator so that the investigator can properly 
store your research information.  
 
Choosing not to be in this study or to stop being in this study will not result in any penalty to you or loss 
of benefit to which you are entitled. This means that your choice not to be in this study will not 
negatively affect your right to any present or future dental care, your academic standing as a student, or 
your present or future employment. 
 
What are the risks of being in this study?  Is there any way being in this study could be 
bad for me? (Detailed Risks) 
 
Risk associated with SRP, clinical measurements and  teeth cleaning 
You should experience no more discomfort related to having SRP, clinical measurements of your gum 
tissue, having your teeth cleaned, or having minocycline HCl microspheres, 1 mg placed than you would 
compared to your regular dental visit. The researchers will try to minimize these risks by utilizing 
standard of care methods.  
 
Risks associated with saliva, fluid around teeth, and blood draw 
Saliva and fluid around your teeth is non-invasion and not painful. You should experience no more 
discomfort or risks related to having your blood drawn than you would compared to any other medical 
appointment. You may experience bruising, dizziness, faintness, or on a rare occasion an infection.  
 
Risks of placement of minocycline HCl microspheres, 1 mg 
You should experience no more discomfort related to having minocycline HCl microspheres, 1 mg placed 
than you would compared to your regular dental visit. The researchers will try to minimize these risks by 
utilizing standard of care methods. The following side effects have been reported with minocycline 
products: swelling, rash, papules, reddening, difficulty breathing, or other signs and symptoms of 
possible hypersensitivity may occur.  
There are additional risks for pregnant women and mothers who are breastfeeding; therefore these 
individuals will not be eligible to participate in this study.  
 
As with any research study, there may be additional risks that are unknown or unexpected. 


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Will it cost me anything to participate in this research study? 
Taking part in this research study will not lead to any costs to you. If you are enrolled in the study, you 
will get a parking pass for the Washington Avenue parking ramp.  
 
You and your insurance company will be charged for the health care services that you would ordinarily 
be responsible to pay. In some cases, insurance will not pay for services ordinarily covered because 
these services are performed in a research study. You should check with your insurance to see what 
services will be covered by your insurance and what you will be responsible to pay. 
 
What happens to the information collected for the research? 
Efforts will be made to limit the use and disclosure of your personal information, including research 
study and dental records, to people who have a need to review this information. We cannot promise 
complete confidentiality. Organizations that may inspect and copy your information include the 
Institutional Review Board (IRB), the committee that provides ethical and regulatory oversight of 
research, and other representatives of this institution, including those that have responsibilities for 
monitoring or ensuring compliance. Other organizations that will have access to your information 
include Fairview clinical laboratory, Access Genetics laboratory, and Bausch Health Companies, Inc.    
 
Data or Specimens Collected 
Your information or de-identified data as part of this research may be used  for future research studies. 
Samples that are collected will not be distributed.  
 
The sponsor, monitors, auditors, the IRB, the UMN Compliance Office and other University compliance 
units, the US Office of Research Integrity (ORI), the US Office for the Protection of Human Research 
Protections (OHRP), the US Food and Drug Administration (FDA) may be granted direct access to your 
medical records to conduct and oversee the research. By signing this document you are authorizing this 
access. We may publish the results of this research. However, we will keep your name and other 
identifying information confidential. 
 
A description of this clinical trial will be available at http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time. 
 
Genetic Information 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal for 
health insurance companies, group health plans, and most employers to discriminate against you based 
on your genetic information. This law generally will protect you in the following ways: 
• 
Health insurance companies and group health plans may not request your genetic information 
that we get from this research. 
• 
Health insurance companies and group health plans may not use your genetic information when 
making decisions regarding your eligibility or premiums. 
• 
Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms of 
your employment. 
• 
Be aware that this federal law does not protect you against genetic discrimination by companies 


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that sell life insurance, disability insurance, or long-term care insurance. 
 
Will I receive research test results? 
Most tests done on samples in research studies are only for research and have no clear meaning for 
health care.  If the research with your identifiable information or samples gives results that do have 
meaning for your health, the investigators will contact you to let you know what they have found. You 
will have the choice of receiving a portfolio of your oral pathogenic burden after the last study visit for 
completing all study visits.    
 
Whom do I contact if I have questions, concerns or feedback about my experience? 
This research has been reviewed and approved by an IRB within the Human Research Protections 
Program (HRPP). To share feedback privately with the HRPP about your research experience, call the 
Research Participants’ Advocate Line at 612-625-1650 or go to 
https://research.umn.edu/units/hrpp/research-participants/questions-concerns. You are encouraged to 
contact the HRPP if:  
● Your questions, concerns, or complaints are not being answered by the research team. 
● You cannot reach the research team. 
● You want to talk to someone besides the research team. 
● You have questions about your rights as a research participant. 
● You want to get information or provide input about this research. 
 
Will I have a chance to provide feedback after the study is over?  
The HRPP may ask you to complete a survey that asks about your experience as a research participant. 
You do not have to complete the survey if you do not want to. If you do choose to complete the survey, 
your responses will be anonymous.   
If you are not asked to complete a survey, but you would like to share feedback, please contact the 
study team or the HRPP. See the “Investigator Contact Information” of this form for study team contact 
information and “Whom do I contact if I have questions, concerns or feedback about my experience?” of 
this form for HRPP contact information. 
Can I be removed from the research? 
The person in charge of the research study or the sponsor can remove you from the research study 
without your approval. Possible reasons for removal include: 
• The researcher believes that it is not the best interest of the participant to stay in the 
study 
• If the participant becomes ineligible to participate based on the exclusion 
criteria 
• If the participant’s medical condition requires interventions which preclude 
involvement in the study (antibiotic therapy or diagnosis of cardiac condition) 
• If the participant does not follow study related instructions 
• The study is suspended or canceled 
We will tell you about any new information that may affect your health, welfare, or choice to stay in the 
research. 
 


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What happens if I am injured while participating in this research? 
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 physicians know right away.   
Will I be compensated for my participation?  
If you agree to take part in this research study, you will receive a $50 gift card after completion of the 1 
month and 3 month visits. You will also get a $100 gift card for completing ALL research visits and for 
your time and effort after the 6 month visit. The total you could receive is $200 for all research visits.  
 
Payment you receive as compensation for participation in research is considered taxable income. If 
payment to an individual equals or exceeds $600 in any one calendar year, the UMN is required to 
report this information to the Internal Revenue Service (IRS). Research payments to study participants 
that equal or exceed $600 during any calendar year will result in a FORM 1099 (Miscellaneous Income) 
being issued to you and a copy sent to the IRS. 
 
Use of Identifiable Health Information 
We are committed to respecting your privacy and to keeping your personal information confidential.  
When choosing to take part in this study, you are giving us permission to use your personal health 
information which includes health information in your medical records and information that can identify 
you. For example, personal health information may include your name, address, phone number or social 
security number. Those persons who get your health information may not be required by Federal 
privacy laws (such as the 1099 Rule) to protect it. Some of those persons may be able to share your 
information with others without your separate permission. Please read the HIPAA Authorization form 
that we have provided and discussed.  
 
The results of this study may also be used for teaching, publications, or for presentation at scientific 
meetings.   
 
Optional research activity 
The research study that you are participating might have optional research activities associated with it, 
meaning that you do not have to agree to these activities in order to participate in the research study.  
Please indicate your willingness to participate in these optional activities and authorize use of your 
information from these optional activities as described below by placing your initials next to each 
activity.    
 
Yes, 
 
No, 
I agree  
I disagree 
☐ 
☐ 
  
 
The investigator for this research may contact me in the future to see whether I am interested in 
participating in other research studies by the investigator. 
 
 


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Your signature documents your permission to take part in this research.  You will be provided a copy of 
this signed document. 
 
_______________________________________________      __________________ 
Signature of Participant                                                                   Date 
 
_______________________________________________ 
Printed Name of Participant 
 
 
____________________________________________            __________________ 
Signature of Person Obtaining Consent                                       Date 
 
______________________________________________________ 
Printed Name of Person Obtaining Consent 

Prot_004.pdf: 
PROTOCOL TITLE: Effect of Non-Surgical Periodontal Therapy With and Without 
Minocycline HCl Microspheres, 1 mg on Bacterial Load and Systemic Markers of 
Inflammation 
VERSION DATE: September 26, 2022 
 
Page 1 of 13 
Template Revised On: 7/26/2018 
 
 
 
 


PROTOCOL TITLE: Effect of Non-Surgical Periodontal Therapy With and Without 
Minocycline HCl Microspheres, 1 mg on Bacterial Load and Systemic Markers of 
Inflammation 
VERSION DATE: September 26, 2022 
 
Page 2 of 13 
Template Revised On: 7/26/2018 
PROTOCOL COVER PAGE 
 
 
 
 
Protocol Title 
Effect of Non-Surgical Periodontal Therapy With and Without 
Minocycline HCl Microspheres, 1 mgon Bacterial Load and 
Systemic Markers of Inflammation 
Principal 
Investigator/Faculty 
Advisor 
Name: Michelle Arnett (PI) and Christine Blue (Co-PI) 
Department: School of Dentistry, Primary Care 
Telephone Number: 612-624-3457 
Email Address: marnett@umn.edu 
Student 
Investigator 
Name: N/A 
Current Academic Status (Student, Fellow, Resident): N/A 
  
Department: N/A 
Telephone Number: N/A 
Institutional Email Address: N/A 
Scientific 
Assessment 
HRPP facilitated scientific assessment 
IND/IDE # (if 
applicable) 
N/A 
IND/IDE Holder 
N/A 
Investigational Drug 
Services # (if 
applicable) 
N/A 
Version 
Number/Date: 
Version 1.4 
April 8, 2020  
 


PROTOCOL TITLE: Effect of Non-Surgical Periodontal Therapy With and Without 
Minocycline HCl Microspheres, 1 mg on Bacterial Load and Systemic Markers of 
Inflammation 
VERSION DATE: September 26, 2022 
 
Page 3 of 13 
Template Revised On: 7/26/2018 
REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
1.2 
September 8, 
2019 
Page 9 was revised to state patient 
charts that are pre-screen and 
have a email address will be 
emailed to subjects instead of sent 
by mail. Page 9 was also revised to 
state the study information will be 
posted on the U of M OHCRC 
website. 
No 
1.3 
February 21, 
2020 
Page 7 was revised to include the 
use of de-identified data for future 
research.  
Yes 
1.4 
April 8, 2020 
COVID-19 plan to mitigate risks on 
page  
No 
1.5 
September 8, 
2022 
Add MMP-8 to GCF and serum 
biomarkers 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PROTOCOL TITLE: Effect of Non-Surgical Periodontal Therapy With and Without 
Minocycline HCl Microspheres, 1 mg on Bacterial Load and Systemic Markers of 
Inflammation 
VERSION DATE: September 26, 2022 
 
Page 4 of 13 
Template Revised On: 7/26/2018 
Table of Contents 
 
1.0 
Study Intervention(s)/Investigational Agent(s) ....................................................... 6 
2.0 
Local Procedures Involved and Local Requirements ............................................... 7 
3.0 
Provisions to Monitor the Data to Ensure the Safety of Participants ..................... 7 
4.0 
Data and Specimen Banking .................................................................................... 7 
5.0 
Sharing of Results with Participants ........................................................................ 8 
6.0 
Local Study Population............................................................................................. 8 
7.0 
Vulnerable Populations ............................................................................................ 8 
8.0 
Local Number of Participants................................................................................... 9 
9.0 
Local Recruitment Methods ..................................................................................... 9 
10.0 Withdrawal of Participants .................................................................................... 10 
11.0 Risks to Participants ............................................................................................... 10 
12.0 Potential Benefits to Participants .......................................................................... 11 
13.0 Confidentiality ........................................................................................................ 11 
14.0 Provisions to Protect the Privacy Interests of Participants ................................... 11 
15.0 Compensation for Research-Related Injury ........................................................... 11 
16.0 Consent Process ..................................................................................................... 11 
17.0 Setting .................................................................................................................... 12 
18.0 Multi-Site Research ................................................................................................ 12 
19.0 Resources Available ............................................................................................... 12 
 


PROTOCOL TITLE: Effect of Non-Surgical Periodontal Therapy With and Without 
Minocycline HCl Microspheres, 1 mg on Bacterial Load and Systemic Markers of 
Inflammation 
VERSION DATE: September 26, 2022 
 
Page 5 of 13 
Template Revised On: 7/26/2018 
ABBREVIATIONS/DEFINITIONS 
AE 
Adverse Event/Adverse Experience 
FDA 
Food and Drug Administration 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SCR 
Scheduled Continuing Review 
US 
United States 
SRP 
Scaling and Root Planing 
GCF 
Gingival Crevicular Fluid 
hsCRP 
High Sensitivity C-Reactive Protein 
Hp 
Haptoglobin 
Hgb Alc 
Hemoglobin A1c 
MMP-8 
Matrix metalloproteinase-8 
TNF-α 
Tumor Necrosis Factor alpha  
IL-1 
Interleukin 1 
IL-6 
CVD 
Interleukin 6 
Cardiovascular disease 
U of M 
University of Minnesota 
School of Dentistry 
SoD 
 
 


PROTOCOL TITLE: Effect of Non-Surgical Periodontal Therapy With and Without 
Minocycline HCl Microspheres, 1 mg on Bacterial Load and Systemic Markers of 
Inflammation 
VERSION DATE: September 26, 2022 
 
Page 6 of 13 
Template Revised On: 7/26/2018 
1.0 
Study Intervention(s)/Investigational Agent(s) 
1.1 Description:  
The primary goal of this study is to investigate the qualitative and 
quantitative effects of SRP with and without minocycline HCL 
microspheres, 1 mg on periodontal pathogens and overall bacterial load. 
A randomized controlled clinical trial of a control (scaling and root planing) 
(SRP)) group and an experimental (SRP with minocycline HCl microspheres, 
1 mg) group is planned. 
 
The intervention of minocycline HCl microspheres, 1 mg will be 
administered in the experimental group at baseline and the three month 
periodontal maintenance visit. Saliva samples, gingival crevicular fluid 
(GCF), and blood serum will be collected at four time points (baseline, 1, 3, 
and 6 month follow up). Saliva will be analyzed for overall pathogen 
burden. GCF will be analyzed for IL-1, IL-6, TNF-α, MMP-8. Serum will be 
analyzed for C-reactive protein (hsCRP), haptoglobin (Hp), hemoglobin 
(Hgb) Alc,  IL-1, IL-6, TNF-α, and MMP-8.  
 
Primary: Investigate the pathogenic burden and overall bacterial load 
utilizing the MyPerioPath® salivary test as a measure of the effect of SRP 
with and without minocycline HCl microspheres, 1 mg. 
 
Secondary: Evaluate the effects of SRP with and without minocycline HCl 
microspheres, 1 mg on serum biomarkers of systemic inflammation, 
including IL-1, IL-6, TNF-α, MMP-8, hsCRP, Hp, and Hgb A1c  and GCF levels 
of IL-, IL-6, TNF-α, MMP-8. 
1.2 Drug/Device Handling:  
Minocycline HCl microspheres, 1 mg are approved by the Food and Drug 
Administration (FDA) as an adjunct to SRP procedures for reduction of 
pocket depth in patients with adult periodontitis. Minocycline HCL, 1 mg is 
a subgingival unit dose of 4 mg of drug containing 1 mg of minocycline and 
3 mg of poly (glycolide-co-dl-lactide) (PGLA). The drug is in a powder form 
and prepackaged in a disposal plastic cartridge tip. The tip is loaded into a 
stainless steel spring- loaded cartridge handle to deliver subgingivally. The 
packaging is clearly labeled for the administration of the drug.  
 
Minocycline HCL, 1 mg will be stored in a locked cabinet in the U of M SoD 
Oral Health Clinical Research Clinic (OHCRC) at room temperature (68o to 
77o F). The product will not be exposed to heat or pressure. 


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The drug is prepackaged and no preparation is required. The prepackaged 
drug is located inside a disposal plastic cartridge tip to ensure exact dosage 
delivered. The tip is loaded into a stainless steel spring-loaded cartridge 
handle to deliver subgingivally.  
 
1.3 Biosafety: N/A 
1.4 Stem Cells: N/A 
 
2.0 
Local Procedures Involved and Local Requirements 
2.1 Local Procedures:  
All study procedures are located on page 14-16 of the protocol.  
2.2 Individually Identifiable Health Information:  
 
Identifiable information from the PHI will be used for recruitment. PHI 
information used for research purposes will be age and gender. See the 
HIPCO Survey and permission to use PHI for research and HIPAA 
authorization form uploaded in ETHOS. Subjects who agree to participate in 
the study will also sign the HIPAA authorization. 
 
2.3 Use of radiation: N/A 
2.4 Use of Center for Magnetic Resonance Research: N/A 
3.0 
Provisions to Monitor the Data to Ensure the Safety of Participants 
3.1 Data Integrity Monitoring.  
The specimen collect, data, and monitoring plan is located on page 21-24. 
Additionally the use of de-identified data for future research. The adverse 
events definitions are located on page 20. Additional information is on 
page 20 under the header ASSESSMENT OF SAFETY.  
3.2 Data Safety Monitoring.  
This study does not include a DSMA or DSMC. However, the data safety 
plan is on page 20-24 of the protocol and can be found on the HIPCO 
Survey. 
3.3     See page 5-6 of the protocol for the plan to mitigate COVID-19 risks. 
 
4.0 
Data and Specimen Banking 


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4.1 Storage and Access: N/A 
4.2 Data: N/A 
4.3 Release/Sharing: N/A 
5.0 
Sharing of Results with Participants 
5.1 The results of this study could be published in an article, but results will  
not be disclosed to participants. If the participants elects a portfolio of their 
oral pathogenic bacteria burden and inflammatory markers a written 
request will be obtained. See page 16 of the protocol.  
6.0 
Local Study Population 
The inclusion and exclusion criteria is on page 9 of the protocol. The premature 
exclusion criteria, handling of participant withdrawals, and premature 
termination or suspension is located on page 11. The screening procedures are 
found on page 14. 
 
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 


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☒ Students of the researcher 
☐ None of the above 
6.1 Additional Safeguards:  
Students and patients of study team members will have equal opportunity 
to participate if they elect to enroll and meet the inclusion criteria. 
7.0 
Local Number of Participants 
7.1 Local Number of Participants to be Consented:  
A sample size of 30 in each group will have 80% power to detect a 
difference in means of 0.736 standard deviations using a two group t-test 
with a 0.05 level of significance. In addition, with an estimated 20% 
attrition rate, we may enroll up to 75 participants. 
8.0 
Local Recruitment Methods 
8.1 Recruitment Methods: 
A U of M Institutional Review Board (IRB) for full or partial waiver of HIPAA 
and protected health information (PHI) will be requested for pre-screening.  
 
As part of the pre-screening process, charts of patients of record at the U 
of M SoD will be reviewed for inclusion criteria. Participants who may be 
eligible to participate will have an invitation letter mailed to them or 
emailed requesting participation.  
 
In addition, a follow-up phone call will me made 1-2 weeks after the 
invitation letter is mailed or emailed. All potential participants will have the 
option to opt out of participation.  
 
Flyers will be posted on each floor of the U of M SoD with study 
participation and contact information. Also, patients currently receiving 
oral healthcare in the dental clinics may be approached by a study team 
member, their assigned student provider, or the attending faculty with a 
flyer inviting them to participate in this study.  
 
Email may be used only after initial contact or with enrolled participant 
permission to use their email for questions or scheduling. Also, email 
communication may be used if an interested person contacts the PI first via 
email from the letter or the flyer.  
The study will also be posted on the U of M Oral Health Clinical Research 
Clinicwebsite. This will allow recruitment of subjects from the surrounding 


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cities near Minneapolis or subjects that may be interested and are not 
patients of record at the U of M SoD. 
See page 9-10 of the protocol.  
 
8.2 Identification of Potential Participants:  
A U of M Institutional Review Board (IRB) for full or partial waiver of HIPAA 
and protected health information (PHI) will be requested for pre-screening. 
A HIPCO survey will be submitted.  As part of the pre-screening process, 
charts of patients of record at the U of M SoD will be reviewed for inclusion 
criteria. Participants who may be eligible to participate will have an 
invitation letter mailed to them requesting participation. In addition, a 
follow-up phone call will me made 1-2 weeks after the invitation letter is 
sent. All potential participants will have the option to opt out of 
participation.  
Interested participants may also self-identify in response to the flyer or 
invitation letter (Page 11 of the protocol).  
• 
Information contained in private/protected records (mailing address) 
will be obtained from AxiUm only after IRB confirm PHI and HIPAA 
waiver to use for recruitment purposes.  
• 
The PI will make initial contact with potential participants. 
 
8.3 Recruitment Materials:  
Recruitment materials are described on page 10 of the protocol and 
uploaded in ETHOS.  
 
8.4 Payment:  
A $50 prepaid ClinCard will be given to each participant at the conclusion 
of the one month and three month follow up visits. At the last visit, a $100 
will be loaded in the ClinCard for completing all study visits. This is noted 
on page 15-16 of the protocol and in the schedule of events on page 29.  
 
9.0 
Withdrawal of Participants 
Participant withdrawal and termination is outline in the premature 
exclusion criteria/participant withdrawal on page 11 of the protocol. 
10.0 Risks to Participants 


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There are no risks greater than the risk of a regular dental visits. Risks are 
described on page of the protocol and in the informed consent form on page 6. 
In addition, research activities are in the protocol on page 14-16. All activities are 
the standard of care and minocycline HCl microspheres, 1 mg will be used in the 
context of the standard of care and FDA approved administration.  
 
11.0 Potential Benefits to Participants 
The potential benefits are on page 5 of the protocol.  
 
12.0 Confidentiality 
 
12.1 Protecting Privacy:  
Protections for confidentiality are on page 22 of the protocol. Protection of 
data are described in the protocol on page 22-24.   
12.2 Access to Participants:  
Having access to dental records of enrolled/consented participants is 
needed to conduct the study and maintain the standard of care.  
13.0 Compensation for Research-Related Injury 
13.1 Compensation for Research-Related Injury:  
This study is not greater than minimal risk, however, details regarding a 
research injury is described on page 8 of the informed consent.  
13.2 Contract Language:  
Below is the language from page 8 of the protocol: 
What happens if I am injured while participating in this research? 
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 physicians know right away. 
14.0 Consent Process 
The consent process is on page 14 of the protocol. The consent process and all 
study visits will take place at the U of M SoD Oral Health Clinical Research Clinic 
(OHCRC).  
 
14.1 Consent Process (when consent will be obtained): N/A 


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14.2 Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A 
14.3 Waiver of Written/Signed Documentation of Consent (when written/signed 
consent will not be obtained): N/A  
14.4 Non-English Speaking Participants: N/A 
14.5 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): N/A 
14.6 Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: N/A 
14.7 Adults Unable to Consent: N/A 
15.0 Setting 
15.1 Research Sites:  
A convenience sample of up to 75 participants from the University of 
Minnesota (U of M) School of Dentistry (SoD) or outside of the university  
(U of M StudyFinder website) will be invited to participate in this study. The 
goal is two groups of 30 participants. Participants in both groups will have 
four clinical visits over a 6 month period in the U of M SoD Oral Health 
Clinical Research Clinic (OHCRC). Page 13, 14 and 29 of the protocol.  
 
15.2 International Research: N/A 
16.0 Multi-Site Research 
 
N/A 
17.0 Resources Available 
17.1 Resources Available: 
It is feasible to recruit up to 75 periodontal patients from the U of M SoD. 
There is an abundance of patients of record that meet the inclusion 
criteria. In addition, patients from the U of M StudyFinder may participate.  
The PI will have one full clinic day (8 am- 5pm) for research activities. The 
research assistant will have one and half days to recruit, manage study 
documents, and assist in research activities.   
The OHCRC is located at the U of M SoD. It is a dental clinic and has a 
private room to conduct the informed consent process if potential 
participants elect a private room instead of a cubicle.  
https://www.dentistry.umn.edu/research/centers-institutes-labs/oral-
health-clinical-research-clinic 


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The U of M SoD is equip if a medical emergency occurred. 
The M Health Clinical Research Unit (CRU) is located on the second floor 
and participants will be escorted to the blood draw visit.  
There will be regular study team meetings on a monthly basis. See the 
monitoring plan on page 17-18 of the protocol.