RAJIV GANDHI UNIVESITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANNEXURE-2

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS
(IN BLOCK LETTERS) / Dr. sneha keshri
POST GRADUATE STUDENT,
DEPARTMENT OF PERIODONTICS,
K.L.E. SOCIETY’S INSTITUTE OF DENTAL SCIENCES, #20,YESHWANTPUR SUBURB,
TUMKUR ROAD BANGALORE -22.
2. / NAME OF THE INSTITUTION / KLE SOCIETY’S INSTITUTE OF DENTAL SCIENCES, BANGALORE -22
3. / COURSE OF THE STUDY
AND SUBJECT / MASTER OF DENTAL SURGERY IN PERIODONTICS
4. / DATE OF ADMISSION TO
COURSE / 27th JULY 2013
5. / TITLE OF THE TOPIC / EVALUATION AND COMPARISON OF SERUM VITAMIN D LEVELS IN CHRONIC PERIODONTITIS WITH TYPE 2 DIABETES MELLITUS AFTER PHASE-I THERAPY AND VITAMIN D SUPPLEMENT - A RANDOMIZED CONTROLLED CLINICAL TRIAL
6. / BRIEF RESUME OF INTENDED WORK
6.1  NEED FOR STUDY :
Periodontal disease resulting from oral bacterial infection is a chronic inflammatory disease that leads to soft and hard tissue breakdown. The concept of “Focal Infection Theory” being revisited has lead to an increasing association between Periodontal disease and systemic conditions and diseases.
Numerous clinical studies have proved and established the fact that Chronic periodontitis (CP) is not just the 6th complication of Type 2 Diabetes mellitus1 but also an existence of a bi-directional relationship between the two entities2.
Current researches have also shown that Vitamin D and calcium supplements have a positive effect on various chronic diseases3, such as Cardiovascular diseases, Chronic Kidney Diseases, Type 2 Diabetes Mellitus (Type 2 DM), Chronic periodontitis etc.4
Adequate Vitamin D (Vit D) levels improve periodontal health, increase bone density in the jaw bone, and inhibit alveolar bone resorption.4
Active Vit D hormone, (1,25-dihydroxyvitamin D) needed for calcium homeostasis in the blood has shown to increase transcription of antimicrobial peptides.5
1,25 (OH)2 Vitamin D also influences hormone secretion, in particular that of insulin, providing a possible mechanism by with low Vit D levels could contribute to the pathogenesis of diabetes.6
Clinical studies have shown an interrelationship between the diabetes mellitus and Vitamin D levels, chronic periodontitis and diabetes mellitus, chronic periodontitis and the use of Vitamin D and calcium supplements but till date none of the studies have been documented showing the effect of Vitamin D supplemental therapy on chronic periodontitis in patients with Type 2 Diabetes Mellitus. Thus through this research an effort is being made to evaluate and Compare the effect of Vit D supplementation as an adjunct to Scaling and Root planing (SRP) and SRP alone on serum levels of vitamin D, periodontal clinical parameters and bone density changes in chronic periodontitis patients with Type 2 Diabetes Mellitus.
6.2 REVIEW OF LITERATURE:
1. A cross-sectional study was done to assess the relationship between ApaI, BsmI, and FokI Vitamin D Recpector (VDR) polymorphisms and the risk of severe chronic periodontitis among Japanese adult men. The results concluded that the VDR haplotype constructed from the ApaI, BsmI, and FokI polymorphisms is related to the risk of severe chronic periodontitis in Japanese men.7
2. A literature review was conducted to evaluate “The Role of Vitamin D in the pathogenesis of Type 2 diabetes mellitus”. They concluded that the alterations in Vitamin D status and/or action may affect insulin sensitivity, b-cell function or both. Furthermore, several vitamin D–related genes have shown associations with
different pathogenetic traits of the disease. Therefore, Vitamin D and its related metabolic and immune pathways may be involved in the pathogenesis of Type 2 diabetes mellitus at both environmental and genetic levels.8
3. A cohort study was done to determine whether the use of Vitamin D and calcium supplements effects periodontal disease status. The results concluded that in the subjects receiving periodontal maintenance therapy, there was a trend for better periodontal health with Vitamin D and calcium supplementation.3
4. A study was conducted to compare and quantify the expression of C-reactive protein (CRP), matrix metalloproteinase (MMP)-14, and tissue inhibitor of metalloproteinases (TIMP)-2 in gingival tissues of patients with chronic periodontitis accompanied with inflammatory reaction related to alveolar bone resorption with or without Type 2 diabetes mellitus (DM). This study demonstrated that the expression levels of CRP, MMP-14, and TIMP-2 might be inflammatory markers in periodontal inflamed tissue. It can be assumed that CRP, MMP-14, and TIMP-2 may be partly involved in the progression of periodontal inflammation associated to Type 2 DM.9
5. A review study focused on associations observed between Vitamin D status and its potential immune-modulating effects in the metabolism of Type 2 diabetes biomarkers. On basis of clinical and epidemiological data, the study concluded that the positive effects of Vitamin D seem to be primarily related to its action on insulin secretion and sensitivity and secondary to its action on inflammation.10
6. In a case-control study the relation between serum Vitamin D levels and CP in patients with predialysis CKD was evaluated. The demographic, clinical and laboratory data were assessed. The results concluded that Vitamin D deficiency is associated with CP in patients with CKD who are not yet on dialysis.4
HYPOTHESIS
·  Null Hypothesis:
·  Vit D supplements has no tangible or intangible added beneficial effect on serum Vit D levels along with the clinical and radiological parameters when used as an adjunct to SRP in the non-surgical management of chronic periodontitis.
·  Alternative Hypothesis:
·  Vit D supplements has a tangible or intangible added beneficial effect on serum Vit D levels along with the clinical and radiological parameters when used as an adjunct to SRP in the non-surgical management of chronic periodontitis.
6.2 OBJECTIVE OF THE STUDY:
1. To evaluate and Compare the effect of Vit D supplement as an adjunct to Scaling and Root planing (SRP) and SRP alone on serum levels of Vitamin D (Vit D) in chronic periodontitis patients with Type 2 Diabetes Mellitus.
2. To evaluate and Compare the effect of Vit D supplement as an adjunct to SRP and SRP alone on Periodontal clinical parameters in chronic periodontitis patients with Type 2 Diabetes Mellitus.
3. To evaluate and Compare the bone density changes in patients undergoing SRP with Vit D supplement and SRP alone in chronic periodontitis patients with Type 2 Diabetes Mellitus.
MATERIALS AND METHODS
7.1  SOURCE OF DATA:
Out-patient division of Department of Periodontics, KLE Society’s Institute of Dental Sciences, Bangalore.
7.2.1 METHODS OF COLLECTION OF DATA (INCLUDING SAMPLING PROCEDURES, IF ANY):
Study Type – In Vivo
Study design – A randomized controlled clinical trial.
Blinding procedure – A double blind study.
Sample size – 60 subjects.
Sampling method – Random sampling.
7.2.2 INCLUSION CRITERIA:
·  Patients with moderate chronic periodontitis and Type 2 diabetes mellitus in the age group of 30 to 65 years.
·  Patients with moderate Chronic periodontitis and Type 2 diabetes mellitus with serum Vit D levels <30 ƞg/mL.
·  Minimum of 20 teeth to be present.
·  Patients with at least two non-adjacent sites per quadrant with probing depth ≥ 5mm and clinical attachment loss of 3-4 mm.
7.2.3 EXCLUSION CRITERIA:
·  Patients who have undergone periodontal therapy in the past 6 months.
·  Subjects on immunosuppressant, antibiotics or any form of supplement
therapy 6 months prior to the study.
·  Chronic Smokers, Alcoholics, Smokeless tobacco users.
·  Subjects with acute illnesses/acute intraoral lesions.
·  Pregnant and lactating subjects.
·  Post-Menopausal women.
·  Subjects with chronic systemic diseases other than Type 2 diabetes mellitus.
7.2.4 DURATION OF STUDY – 1.5 yrs.
7.2.5 STUDY DESIGN:
·  After thorough Screening, 60 subjects of both sexes, satisfying the
inclusion criteria and willing to participate in the study will be
enrolled.
·  These subjects will then be randomly and equally assigned, using
Block Randomization, into two groups Group I (G1) and Group 2 (G2).
Group I (G1):
·  Consisting of 30 subjects with CP and Type 2 DM will be subjected
to SRP alone and placebo for once a week for 10 weeks with a glass of milk.
·  Clinical Parameters will be assessed at baseline, 12 weeks and 6 months
after SRP.
·  Serum levels of Vit D will be assessed at baseline and 12 weeks after SRP.
·  Radiographic assessment using OPG and ImageJ software will be done at
baseline and 6 months.
Group 2 (G2):
·  Consisting of 30 subjects with CP and Type 2 DM will be administered
Vit D supplements in the form of cholecalciferol granules (60,000 I.U. )
once a week for 10 weeks with a glass of milk as an adjunct to SRP.
·  Clinical Parameters will be assessed at baseline, 12 weeks and 6 months
after SRP.
·  Serum levels of Vit D will be assessed at baseline and 12 weeks after SRP.
·  Radiographic assessment using OPG and ImageJ software will be
done at baseline and 6 months.
Patients of both groups will be put on a meticulous oral hygiene regimen.
7.2.6 STUDY METHOD
Biochemical Investigation:
A Blood sample of 2ml will be collected in marked serum vial and transported to the laboratory in ambient temperature.
Venous Blood is drawn from the antecubital fossa or the back of the hand and the sample is assessed using Enzyme-linkedimmunosorbent assay(ELISA) for serum Vit D levels.
The sample will also be subjected to estimation of the Routine Blood glucose levels (HbA1C, FBS and PPBS).
Clinical Examination:
The following clinical parameters will be assessed at at baseline, 12 weeks and 6 months after phase-1 and supplemental therapy:-
- Plaque Index ( PI; Silness and Loe 1964)
-Gingival Index (GI; Loe and Silness 1963)
- Probing pocket depth (PPD)
- Clinical attachment level (CAL)
PD and CAL will be recorded using pressure constant pressure probe (Brock probe™).
Radiographic Analysis:
The changes in Bone density levels will be assessed using ImageJ software developed by NIH (National Institute Of Health), Bethesda, Maryland, USA.
STATISTICAL TESTS THAT WILL BE USED:
·  Intra-group comparison of clinical parameters
Analysis of variance test (ANOVA) / Kruskal Wallis test
·  Intergroup comparison at baseline and 12 and 6 months for clinical parameters-student t test / Wilcoxon signed rank test.
P value <0.05 is considered to be statistically significant.
7.3 Does the study require any investigation or interventions to be conducted on patients or both humans or animals? If so, please describe briefly.
Yes. After thorough explanation of the study protocol, in a language understandable by the patient, a written consent for collection of data and for performing the procedure will be obtained from all the subjects recruited for the study.
The selected individuals will be subjected to SRP followed by placebo and Vitamin D supplementation respectively.
7.4 Has ethical clearance been obtained from your institute in case of 7.3?
Yes.
LIST OF REFERENCES:
1. Loe H. Periodontal disease. The sixth complication of diabetes mellitus.

Diabetes Care. 1993;16(1):329-334.

2. Taylor GW. Bidirectional interrelationships between diabetes and periodontal diseases: An epidemiologic perspective. Ann Periodontol.2001 Dec;6(1):99-112.

3. Miley DD, Garcia MN, Hildebolt CF, Shannon WD, Couture RA, Spearie CLA et al. Cross-sectional study of Vitamin D and Calcium Supplementation effects on Chronic Periodontitis. J Periodontol 2009;80:1433-9.
4. Bastos Jdo A,Andrade LC,Ferreira AP,Barroso Ede A,Daibert Pde C,Barreto PL et al. Serum levels of Vitamin D and chronic periodontitis in patients with chronic kidney disease. J Bras Nefrol. 2013;35(1):20-6
5. Gombart AF. The vitamin D–antimicrobial peptide pathway and its role in protection against infection. Future Microbiol 2009;4:1151-1165.
6. Reid IR,Bolland MJ. Role of Vitamin D deficiency in cardiovascular disease. Heart.2012 Apr;98(8):609-14.
7. Naito M, Miyaki K, Naito T, Zhang L, Hoshi K, Hara A et al. Association between Vitamin D receptor gene haplotypes and chronic periodontitis among Japanese men. Int J Med Sci 2007;4(4):216-222.
8. Palomer X,González-Clemente JM,Blanco-Vaca F,Mauricio D. Role of Vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab. 2008 Mar;10(3):185-97.
9. Kim J, Jung M, Cho J, Park J, Suh J, Lee J. The influence of type 2 diabetes mellitus on the expression of inflammatory mediators and tissue inhibitor of metalloproteinases-2 in human chronic periodontitis. J Periodontal Implant Sci. 2011; 41:109-116

10. Chagas CEA, Borges MC, Martini LA, Rogero MM. Focus on Vitamin D, Inflammation and Type 2 Diabetes. Nutrients2012;4(1):52-67.

9. / SIGNATURE OF CANDIDATE
10. / REMARKS OF THE GUIDE
11. / NAME AND DESIGNATION OF
(IN BLOCK LETTERS)
11.1  GUIDE
11.2  SIGNATURE / DR. SPHOORTHI A. BELLUDI
PROFESSOR
DEPARTMENT OF PERIODONTICS.
KLE SOCIETY’S INSTITUTE OF DENTAL SCIENCES, BANGALORE-22
11.3  CO-GUIDE (IF ANY)
11.4  SIGNATURE / Dr. ASHWIN PRABHU
READER
DEPARTMENT OF PERIODONTICS.
KLE SOCIETY’S INSTITUTE OF DENTAL SCIENCES, BANGALORE-22
11.5  HEAD OF THE DEPARTMENT
11.6 SIGNATURE / DR SUDHIR R. PATIL
PROFESSOR AND H.O.D
DEPARTMENT OF PERIODONTICS.
KLE SOCIETY’S INSTITUTE OF DENTAL SCIENCES, BANGALORE-22
12. / 12.1 REMARKS OF THE
PRINCIPAL
SIGNATURE