Dissertation Synopsis s1
DISSERTATION – SYNOPSIS
DR. PREETHI.S
POST GRADUATE STUDENT
DEPARTMENT OF PERIODONTICS
BATCH 2013-2016
FAROOQIA DENTAL COLLEGE AND HOSPITAL
MYSORE
Rajiv Gandhi University of Health Sciences, Karnataka,
Bangalore
RAJIV GANDHI UNDERSITY OF HEALTH SCIENCES, BANGALORE,
KARNATAKA
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / NAME OF THE CANDIDATE AND ADDRESS / DR.PREETHI.SPOST GRADUATE STUDENT,
DEPARTMENT OF PERIODONTICS,
FAROOQIA DENTAL COLLEGE & HOSPITAL,
UMAR KHAYAM ROAD, EIDGAH, MYSORE – 570 021
2 / NAME OF THE INSTITUTION / FAROOQIA DENTAL COLLEGE & HOSPITAL
UMAR KHAYAM ROAD,
EIDGAH,
MYSORE – 570 021
3 / COURSE OF THE STUDY AND SUBJECT / MASTER OF DENTAL SURGERY IN PERIODONTICS
4 / DATE OF ADMISSION TO COURSE / 26.07.2013
5 / TITLE OF THE THESIS:
COMPARATIVE EVALUATION OF FENFUROTM (HERBAL ANTI-DIABETIC DRUG) AND METFORMIN (ALLOPATHIC ANTI-DIABETIC DRUG) BY LOCAL DRUG DELIVERY AS AN ADJUNCT TO NON-SURGICAL DEBRIDEMENT IN THE TREATMENT OF CHRONIC PERIODONTITIS: A CLINICAL AND RADIOGRAPHIC STUDY.
6
7 / BRIEF RESUME OF THE WORK INTENDED:
6.1 NEED FOR THE STUDY:
Periodontal disease is a chronic inflammatory disease characterized by inflamed gingiva, bleeding on probing, resorption of alveolar bone, and loss of supporting structures of the teeth.
Many treatment modalities are available to achieve the goal of periodontal therapy. This includes non-surgical periodontal therapy, such as scaling and root planing (SRP) alone or SRP plus systemic or local antimicrobial or anti-inflammatory agents and surgical periodontal therapy. Autologous bone is the current gold-standard graft material for the treatment of skeletal defects and fracture repair1. However, the need for a second surgical site and limited supply of bone available have led to the development of various alternative materials.
Protein growth factors (like bone morphogenetic proteins) are expensive, may degrade rapidly at the treatment site, and could potentially elicit immune responses, thus limiting their use2.
If pharmacologic compounds can upregulate the necessary autogenous growth factors to stimulate bone growth, this approach may prove to be a cost-effective way to correct bone defects.
FenfuroTM, a group of furostanolic Saponins (an ayurvedic drug) and Metformin (MF), a second generation biguanide (an allopathic drug), are commonly used oral anti-diabetic drugs that have been recently shown to stimulate osteoblasts and reduce alveolar bone loss.
The aim of this study is to evaluate the effect of FenfuroTM and Metformin as an adjunct to scaling and root planing for its efficacy in treatment of periodontitis are sparse, an attempt to evaluate the same will be done in the present study.
6.2 REVIEW OF LITERATURE:
Periodontal disease is a result of the local bacterial infection with a pathogenic microflora within the periodontal pocket. Traditional therapies for periodontal disease have included mechanical debridement to disrupt the subgingival flora and provide clean, smooth and biologically compatible root surfaces3.
As the nature of the bacterial etiology has become understood, there have been many anti-microbial approaches to disease management as well. Initial approaches included the use of systemic antibodies. It became apparent, however, that the dose is necessary to achieve sufficient local concentration of antibiotic in the periodontal pocket might be associated with undesirable side effects3.
By means of controlled local delivery from within the periodontal pocket, a single administration of a few milligrams of an antibacterial agent can maintain therapeutic concentrations within the crevicular fluid for a longer period of time than any other mode of delivery4.
During recent years, many pharmacological compounds have been shown to be effective in treatment of periodontal disease.
Periodontitis is influenced by many systemic diseases such as diabetes mellitus5.
Diabetes Mellitus is a clinically and genetically hetrogenous group of metabolic disorders manifested by abnormally high levels of glucose in the blood6.
Patients with diabetes have multiple skeletal disorders, including osteopenia, osteoporosis, Charlot’s disease and diffuse idiopathic skeletal hyperostosis7.
FENFUROTM is a group of Furostanolic Saponins, derived from fenugreek seeds, Trigonella Foenum-Graecum. Fenfuro contains a rich variety of saponins and flavonoids having blood cholesterol-lowering and blood glucose-lowering properties.
Al-Sobayil FA in a study conducted to evaluate the effect of fenugreek seeds on the healing of mandibular fracture in male dromedary camels showed that adding fenugreek powder to the ration of these camels significantly stimulated bone formation and inhibited bone resorption8.
METFORMIN HYDROCHLORIDE (1, 1 – dimethyl biguanide HCl), is an anti-hyperglycemic biguanide most commonly used for the treatment of type II diabetes mellitus. The precise mechanism of action of metformin remains unclear. Several sites of action have been proposed for metformin, including decreased hepatic glucose output, increased peripheral glucose uptake and improved insulin secretion9.
A study by Cortizo et al. shows a direct osteogenic effect of metformin on osteoblasts in culture and suggest that these actions could be partly mediated by activation/redistribution of extracellular signal regulated kinase (ERK) – 1/2 and induction of endothelial / inducible nitric oxide synthases (e/i NOS)10.
Ma L et al. have shown that osteoblasts from Sprague-Dawley (SD) rat mandible can transport metformin into cells, and the uptake of metformin in osteoblasts was a secondary active transportation mediated by rat organic cation transporter 1 (rOct 1). High glucose can improve the uptake of metformin by osteoblasts through phosphorylation of rOct 1, which proves the feasibility of the local administration of metformin around dental implant in diabetes patients11.
Gao Y et al. in a study evaluated the effect of metformin on bone mass in ovariectomized rats and found a direct inhibition of metformin on cancellons bone loss12.
Bak EJ et al. in a pilot study to evaluate the effect of metformin on alveolar bone in ligature – induced periodontitis in rat, showed that metformin stimulated osteoblast differentiation13.
Rao AR et al. in a randomized controlled clinical trial to evaluate the efficacy of varying concentrations of metformin to SRP in the treatment of chronic periodontitis showed a significant mean probing depth and bleeding on probing reduction and mean clinical attachment level (CAL) gain at 3 and 6 months and significant reduction in intra bony defect (IBD) depth at 6 months, with greatest reduction in 1% metformin14.
6.3 OBJECTIVES OF THE STUDY:
i. To evaluate the effect of Fenfuro as a local drug delivery system as an adjunct to scaling and root planing (SRP) for treatment of intrabony defects (IBDs) in patients with chronic periodontitis (CP).
ii. To compare the effect of Fenfuro with Metformin as a local drug delivery system in adjunct to SRP for treatment of IBDs in patients with CP.
MATERIALS AND METHODS:
7.1 SOURCE OF DATA:
In this study, 20 patients will be selected, who are diagnosed with chronic generalized periodontitis from the out-patient section of the Department of Periodontics, Farooqia Dental College and Hospital, Mysore, India.
7.2 METHOD OF COLLECTION OF DATA:
20 systemically healthy patients, including both males and females, in the age group of 30-65 years diagnosed with chronic generalized periodontitis will be enrolled in this study.
SAMPLE SIZE:
40 sites from 20 patients will be selected by stratified random sampling.
INCLUSION CRITERIA:
· Patients diagnosed to have chronic periodontitis with 20 remaining teeth.
· Probing depth 5mm
· Clinical attachment level 4mm
· Radiographic evidence of vertical bone loss 3mm
· No history of periodontal therapy in the preceding 6 months.
· No history of any topical or systemic antimicrobial therapy in the preceeding 6 months.
EXCLUSION CRITERIA:
· Patients with known systemic disease.
· Known or suspected allergy to the fenugreek seeds/ metformin / biguanide group.
· Patients on systemic metformin or other oral antidiabetic therapy.
· Patients with aggressive periodontitis.
· Patients using tobacco in any form.
· Alcoholism.
· Immuno-compromised patients.
· Pregnant or lactating females.
MATERIAL:
Metformin gel and Fenfuro gel will be formulated at the JSS College of Pharmacy, Mysore.
STUDY DESIGN:
A split mouth design is considered for the study, two sites in the contra lateral quadrants which require periodontal treatment with probing depth 5mm at baseline will be selected for this study.
METHOD:
· The nature and design of the clinical trial will be explained to the patients and informed consent will be obtained.
· Oral hygiene instructions for supragingival plaque control will be given.
· Two contra-lateral sites will be selected in each patient. Sites will be randomly categorized as:
Category 1: SRP with 1% Metformin gel
Category 2: SRP with Fenfuro gel
· The pocket depth will be measured using a standard UNC-15 graduated periodontal probe and a custom made acrylic stent will be used for standardization.
· Full mouth scaling and root planing will be done at baseline to prevent cross infection of the sites.
· The patient will not be prescribed any antibiotics and/or anti-inflammatory agents after treatment.
· The patient will be instructed to refrain from chewing hard or sticky food for 1 week.
· The patient will be instructed not to use any other plaque control methods other than normal brushing and rinsing.
· Acrylic stents will be fabricated to standardize the entry of probe into the periodontal pockets during recall visits.
The following clinical parameters will be used to assess the periodontal status. The parameters will be recorded at baseline, 3 months and 6 months.
i. Modified sulcus bleeding index: Mombelli, M.A.Van Oosten, E.Schurch Jr., N.P.Land (1987).
ii. Full mouth and site specific plaque score: Silness and Loe (1964).
iii. Gingival index: Loe and Silness (1963)
iv. Probing depth: Using UNC-15 probe
v. Clinical attachment level: Ramjford method.
RADIOGRAPHIC ASSESSMENT OF INTRA BONY DEFECTS (IBD):
The depth of IBD will be evaluated at baseline and 6 months and 9 months using standardized radiographs.
IBD depth will be measured on the radiograph by measuring the vertical distance from the crest of the alveolar bone to the base of the defect.
Individually customized bite blocks and a parallel angle technique will be used to obtain films as reproducible as possible.
STATISTICAL ANALYSIS: Will be done.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON HUMANS OR ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY.
YES
· Oral examination will be done using mouth mirror and UNC-15 probe
· Radiographs will be taken
· Scaling and root planing will be done
· The participant of the study will be requested to fill a consent form.
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION? (ATTACH THE CERTIFICATE).
YES
8 / LIST OF REFERENCES:
1. Alam S, Ueki K, Nakagawa K, et al. Statin-induced (BMP 2) Bone Morphogenic Protein 2 expression during bone regeneration: An immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: 22-29.
2. Garnett IR, Guteirezz G, Mundy GR. Statins and bone formation. Curr Pharm Des 2001; 7: 715-736.
3. Finkelman R D, Williams R C. Local delivery of chemotherapeutic agents in periodontal therapy: Has its time arrived?. J Clin Periodontol 1998; 25: 943-946.
4. J M Goodson, S Offenbacher, D H Farr and P E Hogan. Periodontal disease treatment by local drug delivery. J Periodontol 1985: 265-272.
5. Lamster IB, Lalla E, Borgnakka WS, Taylor GW. The relationship between oral health and diabetes Mellitus. J Am Dent Assoc 2008; 139 (Suppl): 195-245.
6. Mealey BL, Ocampo GL. Diabetes Mellitus and periodontal disease. Periodontol 2000, 2007; 44: 127-153.
7. Rakel A, Sheehy O, Rahme E and Le Lorier. Osteoporosis among patients with type 1 and type 2 diabetes. J diabetes and Metabolism 2008; 34: 193-205
8. Al Sobayil FA. Accelerative effect of fenugreek seeds on the healing of mandibular fracture in male dromedary camels and monitoring of the healing by bone biomarkers. Research J Medicinal Plant 2008; 2 (2): 92-99.
9. Bailey CJ, Turner RC. Metformin. N Engl J Med 1996; 334: 574-579.
10. Cortizo AM, Sedlinsky C, Mc Carthy AD, Blanco A, Schurman L. Osteogenic actions of the anti-diabetic drug Metformin on osteoblasts in culture. Eur J pharmacol 2006; 536: 38-46.
11. Ma L, Wu X, Ling-Ling E, Wang DS, Liu HS. The transmembrane transport of metformin by osteoblasts from rat mandible. Arch Oral Biol 2009; 54: 951-962.
12. Gao Y, Li Y, Xue J, Jia Y, Hu J. Effect of the anti-diabetic drug Metformin on bone mass in ovariectomized rats. Eur J of pharmacol 2010; 635: 231-236.
13. Bak EJ, Park HG, Kim M, et al. The effect of metformin on alveolar bone in ligature induced periodontitis in rats: A pilot study. J Periodontol 2010; 81: 412-419.
14. Rao AR, Rao NS, Naik BS and Kumari M. Efficacy of varying concentrations of subgingivally delivered metformin in the treatment of chronic periodontitis: A randomized controlled clinical trial. J Periodontol 2013; 84: 212-220.
FAROOQIA DENTAL COLLEGE AND HOSPITAL, MYSORE.
Department of Periodontics
PATIENT CONSENT FORM
I ______aged ______years, on my own volition hereby give consent to be a part of the clinical study conducted by PREETHI. S, titled “COMPARATIVE EVALUATION OF FENFUROTM (HERBAL ANTIDIABETIC DRUG) AND METFORMIN (ALLOPATHIC ANTIDIABETIC DRUG) BY LOCAL DRUG DELIVERY AS AN ADJUNCT TO NON SURGICAL DEBRIDEMENT IN THE TREATMENT OF CHRONIC PERIODONTICS: A CLINICAL AND RADIOGRAPHIC STUDY”
I have been thoroughly briefed about the procedure including the complications, if any. I volunteer to be a part of the study and present myself for reviews when required.
Patient’s signature :
Name :
Address :
Contact No :
Attending Doctor’s Signature:
Doctor’s Contact No:
Signature of witness: Date:
FAROOQIA DENTAL COLLEGE AND HOSPITAL, MYSORE.
Department of Periodontics
PATIENT INFORMATION SHEET
You are being requested to take part in a study titled “COMPARATIVE EVALUATION OF FENFUROTM (HERBAL ANTIDIABETIC DRUG) AND METFORMIN (ALLOPATHIC ANTIDIABETIC DRUG) BY LOCAL DRUG DELIVERY AS AN ADJUNCT TO NON SURGICAL DEBRIDEMENT IN THE TREATMENT OF CHRONIC PERIODONTICS: A CLINICAL AND RADIOGRAPHIC STUDY”. Thus the aim of the study is to evaluate the effects of Fenfuro and Metformin as an adjunct to scaling and root planing for its efficacy in the treatment of periodontitis. This study will not alter your treatment plan. Such a procedure is done as a part of the treatment. This study shall only assess the outcome of your treatment procedure.