Combination Of One’s Own Dentin Autograft, I-PRF,A-PRF plus Along With & Without The Use Of A Commercial Drug, Simvastatin To Enhance Bone Formation In Socket Preservation Procedure.
Scientific Title of Study
A Clinico-Radiographic Evaluation Of Dentin Autograft, I-PRF, A-PRF plus With And Without Simvastatin In Socket Preservation: A Randomized Controlled Trial
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NIL
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
DeepthiM
Designation
PG
Affiliation
Rajiv Gandhi university of health sciences
Address
room no - 5 bapuji dental college and hospital
Davanagere KARNATAKA 577004 India
Phone
09731797966
Fax
Email
deepthi4111995@gmail.com
Details of Contact Person Scientific Query
Name
Dr Triveni MG
Designation
Proffessor
Affiliation
Rajiv Gandhi university of health sciences
Address
room no - 5
Department pf periodontics,
Bapuji dental college and hospital
Davanagere KARNATAKA 577004 India
Phone
9449019711
Fax
Email
2012mgtriveni@gmail.com
Details of Contact Person Public Query
Name
Deepthi M
Designation
PG
Affiliation
Rajiv Gandhi university of health sciences
Address
room no - 5
Department of periodontics,
Bapuji dental college and hospital
Davangere
Davanagere KARNATAKA 577004 India
Phone
09731797966
Fax
Email
deepthi4111995@gmail.com
Source of Monetary or Material Support
Out-Patient Department of Periodontics,
Bapuji Dental College and Hospital, Davangere
Primary Sponsor
Name
Deepthi M
Address
Room no 5, Bapuji dental college and hospital, davangere
Type of Sponsor
Other [Self]
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Deepthi M
Bapuji Dental college and hospital
Room no.5,
Department of periodontics,
Davanagere KARNATAKA
9731797966
deepthi4111995@gmail.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Institutional review board, Bapuji dental college and hospital, davangere
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Tooth indicated for extraction
Patients
(1) ICD-10 Condition: K084||Partial loss of teeth,
Intervention / Comparator Agent
Type
Name
Details
Intervention
socket preservation with 1.2mg simvastatin
combination of dentin autograft, i-PRF,
A-PRF+, simvastatin is used for socket preservation.
clinical and CBCT measured at baseline and 4 months follow up
Comparator Agent
socket preservation without simvastatin
combination of only dentin autograft, i-PRF, A-PRF+ is used for socket preservation
clinical and CBCT measured at baseline and 4 months follow up
Inclusion Criteria
Age From
20.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
solated or multiple alveolar sockets of maxillary and mandibular single or multirooted
teeth, indicated for extraction, with at least 7 mm residual alveolar bone height as measured
clinically or radiographically.
Residual extraction sockets possessing intact bone in all dimensions(all four walls) with
alveolar bone more than 50 % of the root length.
The indications for tooth extraction were root fracture and non restorable, periodontitis,
and prosthetic reasons.
Patient with no systemic diseases (eg- uncontrolled diabetes, uncontrolled hypertension
and bleeding disorders).Patient with good oral hygiene (plaque index <1.9).
ExclusionCriteria
Details
Patients who are smokers(more than 10 cigarettes per day), chronic alcoholics.
Endodontically treated teeth indicated for extraction.
Absence of more than 50% of buccal bone.
Patients on drug therapy (like bisphosphonates, antiplatelets, anticoagulants,
immunosuppressants) which can affect the outcome.
Pregnant women and lactating mothers.
Patients not willing for the study or not available for follow up.
Method of Generating Random Sequence
Coin toss, Lottery, toss of dice, shuffling cards etc
Method of Concealment
Alternation
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate clinically the horizontal width and height of the alveolar socket following the
placement of dentin autograft, i-PRF, A-PRF plus with and without simvastatin.
Baseline and 4 months
Secondary Outcome
Outcome
TimePoints
To compare radiographically, the horizontal width and height of the alveolar socket following the
placement of dentin autograft, i-PRF, A-PRF plus with and without simvastatin.
Baseline and 4 months
Target Sample Size
Total Sample Size="12" Sample Size from India="12" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 2
Date of First Enrollment (India)
31/10/2022
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="4" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Need for the study:
Reduction of alveolar ridge in all dimensions after tooth extraction is a natural consequence of
well-known physiological laws. After healing of an extraction socket, the strain stimulus needed
to maintain bone mass is no longer reached. Thus resulting in reduction of the buccolingual as
well as the apico coronal dimension of the alveolar ridge, post extraction1
.This may jeopardize the
rehabilitation of the edentulous ridge especially the implant therapy, which requires an adequate
three dimensional osseous volume of the alveolar ridge, accompanied by good soft tissue for a
long-term functional results. Alveolar ridge preservation (ARP) techniques are widely used to
overcome this resorption. The various approaches currently used to preserve alveolar ridge include
the use of bone substitute materials, minimally invasive extraction, immediate implant placement,
distraction osteogenesis, and guided bone regeneration (GBR) technique.
Statins, like simvastatin has pleiotropic actions, which include antioxidant, anti-inflammatory,
anticoagulant effect, angiogenesis and anabolic effect on bone. Studies revealed that statins reduce
osteoclast activity and activate osteoblast differentiation and bone formation. They seem to
modulate bone formation by direct increase in the bone morphogenetic protein-2 (BMP-2)
expression. Hence simvastatin loaded PRF has synergistic effect on bone regeneration.2
Teeth can be used as a autogenous graft material. Dentin, the main tooth structure, contains type I
collagen, which promotes new bone regeneration. The chemical composition of bone is quite
similar to that of dentin, consisting of approximately 70% hydroxyapatite, 20% collagen, and 10%
body fluid. The dentin matrix also contains noncollagenous proteins, and these proteins include
various growth factors such as bone morphogenic protein 2, transforming growth factor, that
stimulate osteoinductive activity.
3 4
Platelet rich fibrin (PRF), a second generation platelet concentrate was developed in France by
Choukroun et al in 2001. Since then major development was done in the formulation of liquid
version of PRF. Currently combination of biomaterial with autologous blood has become popular
by changing the relative centrifugation force and time.
5 One such modification in the liquid
preparation of PRF is Injectable PRF (i PRF) which has the ability to release higher concentrations
of various growth factors and induce higher fibroblast migration and expression of PDGF, TGFβ, and collagen1 that stimulates biological functions, such as chemotaxis, angiogenesis,
proliferation, and differentiation.
6 7
The purpose of mixing dentin autograft, i-PRF, A-PRF + is to obtain a solid mass for better
manipulation and adaptation for socket preservation. This favours the biomaterial stability during
regenerative procedures, and also increases the graft mass to fill the socket whereas addition of
simvastatin is majorly to access the bone regenerative potential of the drug in socket preservation.
Hence the aim of this study is to evaluate the clinical and radiographic horizontal and vertical
dimensions of alveolar socket by the use of mixture of dentin autograft, i-PRF,A-PRF+ with and
without simvastatin.
6.2 Review of literature:
A study was done to compare the regenerative power of simvastatin and PRF added locally each
as a sole filling material and the combined effect using PRF loaded with simvastatin on an induced
bone defect. critical size bone defect was induced in 48 male albino rats of average weight 150-
200 gm and were divided into 4 groups according to the filling material. Control, PRF, simvastatin,
and simvastatin + PRF group. Each group was subdivided according to the sacrificing period into
two subgroups( one and two months post operatively).Histologically, simvastatin + PRF was the
only group to show significant mature bone formation at 2 months post operatively.
Immunohistochemical analysis, showed highest significant increase in positively stained BMP-2
and VEGF expression in the simvastatin + PRF group. Serum bone anabolic markers increased
significantly in the simvastatin + PRF group. In contrast, RANKL serum level decreased
significantly in the simvastatin + PRF group one month postoperatively. Digital radiograph
revealed the highest BMD(bone mineral density) percent change in the simvastatin + PRF group
and also showed complete bone healing two months post operatively.
2
A study was done to describe the histological and clinical outcome of “dentin block†(a mixture
of autologous particulate dentin, leukocyte- and platelet-rich fibrin (L-PRF), and liquid fibrinogen)
in alveolar ridge preservation. Ten extraction sockets were grafted with “dentin blocksâ€. Two
grafted sites were followed at 4 and 5 months, and 6 sites at 6 months. Histologic( The bone was
compact with normal osteocytes and moderate osteoblastic activity ) and radiographic results
showed that dentin block is a suitable substitute in an alveolar ridge preservation.3
A study was done to demonstrate the regenerative potential of particles obtained from a crushed
extracted tooth. Following tooth removal, the clean root was ground. The dentin and cementum
granules thus obtained was grafted into a fresh extraction socket for a ridge preservation procedure.
The volume of the ridge was preserved. Histologically, a dentin bone complex was reported. New
bone formation was evident, with an intimate contact between bone and both dentin/cementum.4
A study was done to compare Standard PRP and i-PRF (centrifuged at 700 rpm (60G) for 3 min)
for growth factor release up to 10 days (8 donor samples). Furthermore, fibroblast biocompatibility
at 24 h (live/dead assay); migration at 24 hours, proliferation at 1, 3, and 5 days, and expression of
PDGF, TGF-β, and collagen1 at 3 and 7 days were investigated. Growth factor release
demonstrated that in general PRP had higher early release of growth factors whereas i-PRF showed
significantly higher levels of total long-term release of PDGF-AA, PDGF-AB, EGF, and IGF-1
after 10 days. PRP showed higher levels of TGF-β1 and VEGF at 10 days. i-PRF induced
significantly highest migration whereas PRP demonstrated significantly highest cellular
proliferation. Furthermore, i-PRF showed significantly highest mRNA levels of TGF-β at 7 days,
PDGF at 3 days, and collagen1 expression at both 3 and 7 days when compared to PRP. i-PRF
demonstrated the ability to release higher concentrations of various growth factors and induced
higher fibroblast migration and expression of PDGF, TGF-β, and collagen1.7
A comparative study was done to evaluate the clinical efficacy and histological outcome of the
autogenous tooth graft material (AutoBT) to that of anorganic bovine bone in post-extraction
alveolar bone augmentation. A total of 33 graft sites in 24 patients were included in this study.
AutoBT was used in 21 sites of 15 patients and Bio-Oss was used in 12 sites of 9 patients for
alveolar bone. Autogenous demineralized dentin matrix from extracted tooth grafted to extraction
sockets for the augmentation of vertical dimension was as effective as augmentation using
anorganic bovine bone. Both groups showed favourable wound healing, similar amount of implant
stability, and histologically confirmed new bone formation. Thus, the results of this study suggest
that autogenous tooth graft material is a viable option for alveolar bone augmentation following
dental extraction. 8
A study was done to compare growth factor release over time from PRP, PRF and modernized
protocol for PRF, advanced PRF(A-PRF).It was concluded that PRP released more growth factors
when compared to PRF and A-PRF. But A-PRF released significantly higher growth factors and
total protein accumulated over a 10 day period when compared to PRP or PRF.
9
In a study seventy-two patients with mandibular buccal Class II furcation defects were randomized
and categorized into two treatment groups: SRP(scaling and root planning) plus placebo (group 1)
and SRP plus 1.2-mg SMV(simvastatin) (group 2).At baseline and after 6 months, radiologic
assessment of bone defect fill was performed. Thus obtained results showed significantly greater
mean percentage of bone fill in group 2 (25.16%) compared with group 1 (1.54%). Hence
concluding that , locally delivered 1.2-mg SMV, an effective bone fill in the treatment of
mandibular buccal Class II furcation involvement.
10
6.3 Objectives of the study:
• To evaluate clinically, the horizontal width and height of the alveolar socket following the
placement of dentin autograft, i-PRF, A-PRF+ with and without simvastatin, at baseline
and 4 months post operatively.
• To compare clinically, the horizontal width and height of the alveolar socket following the
placement of dentin autograft, i-PRF, A-PRF+ with and without simvastatin at baseline
and 4 months post operatively
• To compare radiographic parameters(horizontal width, vertical height) following the
placement of dentin autograft, i-PRF, A-PRF+ with and without simvastatin at baseline and
4 months post operatively.
Null hypothesis (H0):
Combined effect of dentin autograft, i-PRF, A-PRF+ with simvastatin is not effective when
compared to the effect of dentin autograft, i-PRF,A-PRF+ only when used as a socket graft.
Research hypothesis (H1):
Combined effect of dentin autograft, i-PRF, A-PRF+ with simvastatin is effective when compared
to the effect of dentin autograft, i-PRF,A-PRF+ only when used as a socket graft.
MATERIALS AND METHODS:
7.1 Source of data:
The patients for this study will be selected from Out-Patient Department of Periodontics,
Bapuji Dental College and Hospital, Davangere. Patients will be given a detailed oral and written
description of the risks and benefits of the proposed treatment. Written consent will be obtained
prior to the study.
ESTIMATION OF SAMPLE SIZE11 12:
The sample size estimation was done using previously published literature by Das S et al (palatal
width of the socket measured through CBCT)
t tests - Means: Difference between two independent means (two groups)
Analysis: A priori: Compute required sample size
Input: Tail(s) = Two
Effect size d = 1.8
α err prob = 0.05
Power (1-β err prob) = 0.80
Allocation ratio N2/N1 = 1
Output: Noncentrality parameter δ = 3.1176915
Critical t = 2.2281389
Df = 10
Sample size group 1 = 6
Sample size group 2 = 6
Total sample size = 12
Actual power = 0.8019236
7.2 Method of collection of data
The proposed study will be carried out on patients who are indicated for extraction of single or
multirooted teeth in either maxilla or mandibular arch for future implant placement.
Inclusion criteria:
• Male and female patients within the age group of 20-45 years.
• Isolated or multiple alveolar sockets of maxillary and mandibular single or multirooted
teeth, indicated for extraction, with at least 7 mm residual alveolar bone height as measured
clinically or radiographically.
• Residual extraction sockets possessing intact bone in all dimensions(all four walls) with
alveolar bone more than 50 % of the root length.
• The indications for tooth extraction were root fracture and non restorable, periodontitis,
and prosthetic reasons.
• Patient with no systemic diseases (eg- uncontrolled diabetes, uncontrolled hypertension
and bleeding disorders).
• Patient with good oral hygiene (plaque index <1.9).
Exclusion criteria:
• Patients who are smokers(more than 10 cigarettes per day), chronic alcoholics.
• Endodontically treated teeth indicated for extraction.
• Absence of more than 50% of buccal bone.
• Patients on drug therapy (like bisphosphonates, antiplatelets, anticoagulants,
immunosuppressants) which can affect the outcome.
• Pregnant women and lactating mothers.
• Patients not willing for the study or not available for follow up.
Study Design:
This is a Prospective Randomized Clinical study. Stratification will be done at designed stage by
strict eligibility criteria and randomization of participants. A general assessment of selected
subjects will be made through their history, clinical examination and routine investigations.
Selected sites will be randomly assigned according by coin toss method into two groupsTEST GROUP (A): Will receive mixture of dentin autograft, i-PRF, A-PRF+ with simvastatin
at the extraction socket
CONTROL GROUP (B): Will receive mixture of dentin autograft, i-PRF, A-PRF+ only at the
extraction socket.
Pre-Treatment Records:
• Detailed medical and dental history.
• Routine blood investigations.
• Clotting time
• Bleeding time
• Random blood sugar level
• Diagnostic casts.
• IOPA
• CBCT.
• Clinical photograph.
Presurgical protocol:
Stent fabrication12
Clinical measurement of horizontal, vertical dimensions and relative depth of the socket will be
carried out at baseline and 4 months post-surgery with the help of prefabricated surgical stent.
Acrylic stents will be fabricated using self‑cure clear acrylic resin on the cast models of the
dentition during the treatment planning appointment. The surgical site will be blocked with a layer
of wax to avoid any impingement of the stent on the soft tissue. Prepared acrylic stent will cover
up to 1/3rd of the clinical crown on both buccal and lingual/palatal aspect and will extend to
adjacent teeth on either side of the surgical site. A hole corresponding to the central part of the
alveoli will be made in the prepared acrylic resin stent, and grooves will be prepared on the midbuccal and mid-palatal/mid-lingual aspect of the stent corresponding to the respective cortical
plates. The stent will allow accurate replications of clinical measurements from baseline at the
surgical appointment to 4 months follow up.
Surgical Technique:
Initial surgical site preparation will be done by scrubbing the lower half of the patient’s face using
Betadine (5%) and the patient will be asked to rinse the mouth with 10 ml of 0.2% chlorhexidine
mouthwash. Local anaesthesia (2% lignocaine with epinephrine 1:80,000) will be administered,
following which an atraumatic extraction will be done using periotome. The sockets will be
thoroughly debrided with hand instruments to remove any residual granulation tissue and rinsed
with normal saline. In group A, combination of dentin autograft, i-PRF, A-PRF+ with 1.2mg
simvastatin is used for socket preservation10
. In group B, combination of dentin autograft, i-PRF,
A-PRF+ is used for socket preservation.
Preparation of autogenous tooth graft for immediate grafting:
13
After extraction, the carious lesions and discoloured dentin or remnants of Periodontal ligament
(PDL), calculus and cementum will be removed by tungsten bur . Pulp will be extirpated
endodontically using k fine. In case of multi-rooted teeth the roots can be split. Clean tooth will
be dried by air syringe and put into a grinding sterile chamber ‘Kometa Bio’ for 3 seconds to grind
the tooth and then by vibrating movement of the grinding chamber for 20 seconds the particles of
less than 1200 μm will fall through a sieve to a lower chamber that keeps particles between 300-
1200 μm . The particles less than 300 μm will fall into a waste drawer. This fine particulate (less
than 300 μm) is considered as a non-efficient particulate size for bone grafting. Dentin particles
between 300-1200 μm will be collected in the collecting drawer chamber. Thus collected
particulate dentin from the drawer will then be immersed in basic alcohol cleanser containing of
0.5M of NaOH and 30% alcohol for 10 minutes, in a small sterile glass container. The basic
alcohol cleanser is used for defatting and dissolving all organic debris, bacteria and toxins of the
dentin particulate. After decanting the basic alcohol cleanser, the particulate will be washed twice
in sterile phosphate buffered saline (PBS). It takes approximately 15-20 minutes for the process
from tooth extraction until grafting.
Preparation of i-PRF
10ml of blood samples will be collected in non-coated vacutainer tubes without anticoagulant and
immediately centrifuged at 700 rpm for 3 min.
Preparation of A- PRF +:14
10ml of blood samples will be collected in vacutainer tubes without anticoagulant and immediately
centrifuged at 1300 rpm for 8 min. A-PRF+ membrane or A-PRF+ plug is created by placing the
clots in PRF xpression box.
POST-SURGICAL CARE:
Patients will be asked to refrain from either chewing hard and sticky foods as well as forcefully
brushing at the treated sites until the sutures removed 10 days post-operatively. 10 ml of
Chlorhexidine(0.12%) mouth rinse will be advised twice daily for up to 2 weeks. Follow-up
visits shall be scheduled at one month postoperatively and then at 4 months for clinical and
CBCT(cone beam computed tomography) evaluation. The outcome variables are expressed in
millimeters(mm).
Clinical parameters: 12
Clinically alveolar measurements will be carried out at baseline after extraction and 4 months after
surgical procedure with a fabricated surgical stent.
• Buccolingual width (mm)(vernier caliper)
• Mid buccal crestal height(mm)
• Mid-palatal/lingual crestal height (mm)
• Relative socket depth(mm)
Cone beam computed tomography (Sirona Orthophos SL)12 15
For radiographic analysis, cone beam computed tomography will be used. Patients will be exposed
with 5x5 FOV(Field of view). Multiplanar reconstruction will be done with 1mm thickness.
Images will be captured in high resolution with an exposure time of 14.4 seconds at 10mA current
and 85kV.The voltage, current, exposure time and field of view will be constant at baseline and 4
months post operatively. Analysis of CT scan images will be done using ‘Xelis’ software.
Crestal height will be measured using coronal sections. Crestal width will be measured using axial
and coronal sections.
Radiographically, alveolar socket width, height measurements will be carried out at baseline and
4 months post operatively.
The radiographic parameters are:
• Vertical dimensions of socket:
• Buccal cortical height.
• Palatal/lingual cortical height.
• Socket depth.
• Bucco lingual width
• Buccal plate width 3 levels below the most coronal aspect of the crest:
• At 1mm below the crest
• At 3mm below the crest
• At 5mm below the crest
• Horizontal width of socket measured at 3 levels below the most coronal aspect of the crest:
• At 1mm below the crest
• At 3mm below the crest
• At 5mm below the crest
• Palatal/lingual width 3 levels below the most coronal aspect of the crest:
• At 1mm below the crest
• At 3mm below the crest
• At 5mm below the crest
Statistical analysis:
All parameters will be entered in the standard proforma drawn for this study and will be subjected
to statistical analysis. Intra group and inter group comparison will be done using paired and
unpaired t test.
7.3 Does the study require any investigations or interventions to be conducted on patients
or other humans or animals? If so, please describe briefly.
Yes
• Clinical evaluation of dentin autograft, i-PRF,A-PRF+ with and without simvastatin in
socket preservation
• Complete blood examination.
• Radiographic examination(CBCT).
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