Clinical and Radiographic Evaluation of Demineralized Freeze-Dried Bone Allograft Versus Platelet Rich Fibrin for the Treatment of Periodontal Intrabony Defects in Humans

This entire protocol involves procedures that are standard care. The purpose of the research
is to evaluate whether there are any differences in results of periodontal surgical
treatment using PRF in intrabony defects versus using DFDBA in intrabony defects. The DFDBA
used in this study is an approved product and will be used in an approved manner. The PRF
used in this study is an autologous product derived from the patient's own blood and is also
being used in an approved manner during this study.

The primary outcomes evaluated in this study will include the soft tissue parameter of gain
in clinical attachment level (CAL) and the hard tissue parameter of bone fill (BF).
Secondary outcomes evaluated will include the soft tissue parameters of probing depth (PD)
reduction and change in gingival recession (GR). These parameters will be evaluated over a
6-month period following intraoperative application of the material in advanced periodontal
defects in 44 subjects (22 subjects per group with expected completion of 15 subjects per
group). Six months after surgery, final post-operative clinical and radiographic
measurements will be made.

Each subject will randomly be assigned (1:1) to receive either flap surgery with autologous
platelet-rich fibrin (PRF) placed into the intrabony defect (test) or flap surgery with
demineralized freeze-dried bone allograft (DFDBA) placed into the intrabony defect
(control). Subjects will be randomized by drawing a sealed envelope from a stack of
envelopes, each of which will contain a slip of paper on which is written PRF or DFDBA. The
number of envelopes per group will equal the total number of subjects to be enrolled per
group. Because collection and processing of PRF requires specific equipment, subjects will
be randomized just prior to the surgical procedure being performed (before delivery of local
anesthesia) rather than after flap reflection and debridement.

Each subject will contribute only 1 study site. If a subject has more than one interproximal
bony defect in the area being treated surgically, only 1 such site will be chosen as the
study site. The site with the deepest CEJ-BD measurement will be chosen. All other nonstudy
sites in the surgical area will be treated with the same material as the adjacent study site
(PRF or DFDBA). Clinical measurements at the time of surgery and at the 6-month follow-up
will be made by one of two examiners who are masked as to study group. The same clinical
examiner who makes measurements at the time of surgery will also make measurements at the
6-month follow-up.

Patients will be given post-operative antibiotics for 7 days after surgery as part of
standard care (amoxicillin 500mg three times a day for 7 days; if allergic to amoxicillin,
patients will receive doxycycline 100mg twice a day for 7 days). Subjects will be seen 10-14
days after surgery for routine follow-up procedures including removal of sutures and removal
of visible plaque. Subjects will be followed again for routine postoperative procedures at 1
month, 2 months, and 4 months after surgery. The final postoperative visit will take place
at 6 months post-surgery and will include final radiographic and clinical assessments of the
study site. The study is over after this 6-month follow-up visit.

Routine radiographs will be made as standard care procedures pre-operatively and at the
6-month follow-up time point. Radiographs will be standardized using Rinn XCP holders with
customized bite registrations, and a 1mm radiopaque square grid (Fixott-Everett grid) will
be placed over digital sensor plates to allow ease of linear measurement on the digital
radiographic images. Radiographic measurements will be made by a masked examiner. Hard
tissue measurements made from the radiographs at baseline and 6-month follow-up will include
CEJ to base of bony defect (CEJ-BD).Measurements will be made to the nearest 0.5mm.Bone fill
is the linear change (in mm) in CEJ-BD measurement between baseline examination and 6-month
follow-up.

Soft tissue measurements made at baseline and 6-month follow-up will include probing depth
(PD = gingival margin to base of soft tissue pocket), clinical attachment level (CAL = CEJ
to base of soft tissue pocket), and gingival recession (GR = CEJ to gingival margin) at each
defect site. North Carolina 15mm (UNC-15) periodontal probes will be used and measurements
will be rounded to the nearest 0.5mm.

Intraoperatively, the bony defect will be measured from CEJ-BD to the nearest 0.5mm. This
measurement will be made from both the facial and lingual aspect of the interproximal defect
(i.e., the depth of the interproximal bony defect will be measured from both the facial and
lingual aspect to its deepest depth). In addition, the number of bony walls will be
characterized into one of 7 categories: 1) 1-wall, 2) 2-wall, 3) 3-wall, 4) combination
1,2-wall defect, 5) combination 1,3-wall defect, 6) combination 2,3-wall, or 7)
circumferential defects. At 6-month follow-up, clinical evaluation of bone fill will be made
using transgingival probing in the periodontal pocket from the CEJ to the bony crest. This
measurement will also be made from both the facial and lingual aspect of the interproximal
defect. This standard care procedure is done using topical anesthetic. Surgical re-entry
will not be performed.

For final analysis, the defect will be characterized at the location having the deepest
CEJ-BD measurement at the time of surgery. For example, if treating a defect on the distal
aspect of tooth #19 in which the CEJ-BD measurement is 8.5mm from the facial aspect and
7.5mm from the lingual at the time of surgery, changes in soft tissue parameters (CAL, PD,
recession) and hard tissue parameters (bone fill) for that defect will be determined using
PD, CAL, recession and bone fill measurements taken from the facial aspect only (rather than
using the mean of facial and lingual measurements to characterize the defect).

Inclusion Criteria:

- Patient currently a patient at dental school or eligible for treatment at dental
school

- Patient resides within 50 mile radius of dental school and is eligible for treatment
in Graduate Periodontics Clinic

- Diagnosis of chronic periodontitis with a treatment plan that includes surgical
treatment of an intrabony defect adjacent to a natural tooth

- Willing and able to provide informed consent and be available for multiple follow-up
visits for the duration of the study

- One or more sites with 1) a probing depth of 6mm or greater (>6mm), 2) a radiographic
bony defect depth of greater than 3mm (>3mm), 3) sufficient keratinized tissue to
allow complete coverage of the defect with gingival flaps, and 4) radiographic base
of bony defect at least 2mm coronal to the apex of the tooth

- Female patients who have undergone a hysterectomy, tubal ligation or menopause, and
non-pregnant women of child-bearing potential

Exclusion Criteria:

- not meeting inclusion criteria above

- Failure to attain adequate oral hygiene prior to surgery (minimum 80% plaque-free
surfaces)

- History within the last 6 months of daily use of smokeless tobacco, pipe or cigar
smoking, or cigarette smoking exceeding 10 cigarettes per day. Former smokers who
quit more than 6 months before the study are eligible for enrollment. Current smokers
who smoke less than 10 cigarettes per day are eligible for enrollment.

- Untreated acute or chronic infections in the region of the study site

- Tooth mobility of Grade 2 or higher at the tooth with the potential test site

- Clinical or radiographic signs of apical pathology, root fracture, untreated carious
lesions on the root surface or at the CEJ, subgingival restorations on the tooth with
the potential test site

- Sensitivity or allergy to Bacitracin, Gentamycin, Polymyxin B Sulfate, alcohol and/or
surfactants