Periodontitis and Adverse Pregnancy Outcomes in Metabolic Syndrome Patients- Interventional Study

Metabolic Syndrome Clinical Trial

Official title:

Association Between Periodontitis and Adverse Pregnancy Outcomes in Metabolic Syndrome Patients- Interventional Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03381469
• Other study ID #: MetS in Pregnancy
• Status: Recruiting
• Phase: N/A
• First received: December 11, 2017
• Last updated: February 11, 2018
• Start date: February 10, 2018
• Est. completion date: December 1, 2018

Study information

• Verified date: February 2018
• Source: Riyadh Colleges of Dentistry and Pharmacy
• Contact: Ghousia Sayeed, MDS
• Phone: 00955509731023
• Email: dr_ghousia[@]riyadh.edu.sa
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim The Aim of the current study is to establish the association between periodontitis and adverse pregnancy outcomes in metabolic syndrome (Mets) patients and to evaluate the effect of intervention.

Objectives

1. To evaluate the changes in periodontal status of pregnant women with metabolic syndrome after non surgical periodontal therapy (NSPT)

2. To evaluate the inflammatory marker levels in serum of pregnant women with metabolic syndrome after non surgical periodontal therapy

3. To evaluate the effect of NSPT on adverse pregnancy outcomes of women with metabolic syndrome

Description:

Research Design/Methodology Ethics approval will be obtained from Institution Review Board of Riyadh Colleges of Dentistry and Pharmacy.

Sample size calculation (Green, 1991) By considering the Green's formula as below; Medium effect size (R2=0.07) variance in dependent variable accounted for by the independent variable. Beta weights of (ß=0.20). N≥104+k (Number of independent variable) .Hence total sample size required by considering 8 independent variables will be N=104+8=112. Expecting a patient drop out rate of 30%, the sample size is being increased to 50 patients per group. Approximately 150 patients will be recruited from maternity hospitals of Riyadh City.

Written informed consent will be obtained from patients after explaining the details of the study. Patients will be evaluated using a detailed questionnaire. Demographic characteristics such as age, diet, medical history etc will be recorded. All participants will be interviewed by principal investigator at each visit to capture oral hygiene knowledge and behaviors and exposure to risk factors for adverse pregnancy outcomes. Reviews of medical records will be conducted by principal investigator to record pregnancy history, document the course of the current pregnancy, and record any adverse events. All patients will be advised to report immediately to our dental clinic in case they have any dental related issues during the study period.

Examination Procedure All dental examinations will be performed by principal investigator. Clinical oral examinations will record number of teeth, the number of filled and carious teeth.

Outcome Measures: Periodontal parameters: Gingival Index, Plaque Index, Bleeding on probing, Probing depth (PD), Clinical attachment loss (CAL)

A complete periodontal examination will be conducted with the following assessments:

Bleeding on probing, Probing depth and clinical attachment level will be evaluated at six sites per tooth, whereas plaque index and gingival index will be evaluated at four sites per tooth.

Gingival index (GI). All teeth except third molars will be evaluated for gingival inflammation using a modification of the Loe and Silness , 1963 GI. The GI uses the following scores: 0 = normal gingiva; 1 = mild inflammation; 2 = moderate inflammation; and 3 = severe inflammation.

Plaque index (PI). Prebrushing plaque scores for the buccal surface of each tooth will be assigned using a zero to three scale (Silness and Loe, 1964 ) PI, with ''0''indicating an absence of plaque on the clinical crown and a ''3'' indicating the presence of soft deposits covering more than two-thirds of the crown.

Bleeding on probing (BOP). BOP will be assessed during and recorded after probing measures will be taken for each quadrant. The scoring will be as follows:

0 = absence of bleeding; 1 = bleeding present.

Probing depth. and gingival recession .A manual periodontal probe University of North Carolina -15 probe (UNC-15) , Hu-Friedy, Chicago, Illinois ,will be used to record on all teeth present in the mouth.

Probing depth will be calculated from gingival margin to base of pocket. CAL will be calculated using the clinically detectable cemento-enamel junction (CEJ) as reference and it will be measured from CEJ to base of pocket.

Case definition of Periodontitis outlined by Page & Eke (2007) will be used. The case definition for severe periodontitis requires two or more interproximal sites with CAL > 6 mm, not on the same tooth, and one or more interproximal sites with PD >5 mm. Moderate periodontitis is defined as two or more interproximal sites with CAL >4 mm, not on the same tooth, or two or more interproximal sites with PD >5 mm, not on the same tooth.

Adult Treatment Panel (ATP) III criteria for Mets will be met if an individual has three or more of the following components (Dos Prazeres Tavares et al, 2016):

Abdominal obesity: waist circumference >88 cm (35 inches) in women; Pregestation Body mass index (BMI) > 30kg/m2 High fasting glucose (FPG): serum glucose level > 110 mg/dl (6.1 mmol/l) or on treatment for diabetes; High blood pressure (BP): systolic BP >130 mm Hg and/or diastolic BP >85 mm Hg or on treatment for hypertension (HTN) Hypertriglyceridemia: serum triglyceride level >150 mg/dl (1.69 mmol/l); and Low high-density lipoprotein (HDL) cholesterol: Serum HDL cholesterol <50 mg/dl (1.29 mmol/l) in women.

Clinical data and samples of blood will be collected at three intervals

• At baseline (before 20 weeks gestation)

• 8 weeks after completion of periodontal therapy

• Within 1-2 days of delivery

Serum bio markers: Interleukin-6(IL-6), Prostaglandin-E2 (PG-E2)

Pregnancy Outcomes: Preterm birth < 37 weeks, Low birth weight < 2500 gms, Preterm low birth weight.

The patients and technicians who will perform the lab analyses will be blinded to group assignment.

Study Design It is a randomized clinical trial. Group 1- Case- Periodontitis patients undergoing Comprehensive periodontal treatment Group 2- Control- Periodontitis Patients undergoing single visit supragingival scaling Group 3- Placebo- Patients without Periodontitis undergoing single visit supragingival scaling After the collection of clinical data, the participants will be randomly allocated to either groups of the study using sealed opaque envelopes labeled with a study number and containing the group allocation. Allocations will be computer generated by a third person who will not otherwise be involved in the study. The Case group participants will receive non-surgical periodontal therapy that will be completed by the end of week 20-21 of gestation. This will consist of oral hygiene instruction with comprehensive periodontal treatment which will include excavation and sealing of cavities, removal of overhanging restorations, extraction of hopeless teeth followed by supragingival and subgingival scaling and root planing (SRP) of sites with PDs > 4 mm and polishing of all the teeth. Participants will be offered treatment under local anesthetic when necessary. No limits will be imposed on the number of dental visits needed to accomplish periodontal therapy.

The control and Placebo group participants will receive oral hygiene instruction and supragingival cleaning of all teeth at their baseline visit. Clinical periodontal related data will be collected at a subsequent review appointment 8 weeks after treatment for all groups.

All control participants will be offered the opportunity to attend for comprehensive periodontal therapy postpartum.

Blood samples will be collected after 10 hours of over night fasting. Serum triglyceride, Serum HDL cholesterol and serum glucose will be quantified using standard laboratory procedures in same medical laboratory for all samples collected.

A 5-ml sample of peripheral venous blood will be collected by vein puncture. The blood samples will be centrifuged at 3000 g for 5 min and the serum will be separated. The serum samples will be frozen in plastic vials at -20º Centigrade until further analyzing. Commercially available ELISA assays will be used to measure concentrations of IL-6, and PGE2 in blood samples, according to the manufacturer's recommendations.

Data analysis will be done using Statistical Package for the Social Sciences (SPSS) software. Mean and standard deviation for all clinical parameters. Differences between groups will be assessed using independent t-tests. Sample distribution according to demographic, socio-economic and behavioral data will be assessed using chi-square and Fisher_s exact tests. Between-group differences on the distribution of obstetric data will be assessed using Fisher_s exact test, and differences in adverse pregnancy outcomes will be compared using the independent t-test. Serum bio markers will be presented as median and 25% and 75% percentiles. Differences between groups will be assessed using the Mann- Whitney U-test, and differences among experimental periods will be assessed using the Wilcoxon signed-rank test. The Holm-Bonferroni method will be used to adjust for multiple comparisons. Statistical significance will be set at 5%

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 1, 2018
• Est. primary completion date: August 1, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 34 Years

Eligibility

Inclusion criteria:

• Patients with Mets

• Primi gravida

• Singleton pregnancy < 20 weeks gestation

• 18-34 years of age

• More than 20 teeth in the mouth

Exclusion criteria:

• Previous history of abortion

• Assisted reproduction procedures like fertility medication or in vitro fertilization

• Positive history of HIV

• Positive history of genitourinary infections in previous 6 months

• Any medical contraindication to periodontal probing

• Undergone periodontal treatment or using chlorhexidine or other mouth rinses in the previous 6 months

• Rampant decay

• Taken systemic antibiotic or anti-in?ammatory drugs in the last 6 months before the start of the study, or reported use of phenytoin, cyclosporine, calcium antagonists and/or hormone replacement therapy

• Alcoholics

• Smokers and ex-smokers

• History of kidney, liver or lung disease

• History of any other chronic or acute infections during the previous 6 months as assessed on clinical examination or routine lab testing

Related Conditions & MeSH terms

• Adverse Pregnancy Outcomes
• Birth Weight
• Low Birth Weight Baby
• Metabolic Syndrome
• Metabolic Syndrome X
• Periodontitis
• Pregnancy Complications
• Premature Birth
• Syndrome

Intervention

Procedure:
• Comprehensive periodontal treatment
The Case group participants will receive non-surgical periodontal therapy that will be completed by the end of week 20-21 of gestation. This will consist of oral hygiene instruction with comprehensive periodontal treatment which will include excavation and sealing of cavities, removal of overhanging restorations, extraction of hopeless teeth followed by supragingival and subgingival scaling and root planing (SRP) of sites with PDs > 4 mm and polishing of all the teeth. Participants will be offered treatment under local anesthetic when necessary. No limits will be imposed on the number of dental visits needed to accomplish periodontal therapy.
• single visit supragingival scaling
The control and Placebo group participants will receive oral hygiene instruction and supragingival cleaning of all teeth at their baseline visit.

Locations

Country	Name	City	State
Saudi Arabia	Riyadh Colleges of Dentistry and Pharmacy	Riyadh
Saudi Arabia	Riyadh Colleges of Dentistry and Pharmacy	Riyadh

Sponsors (1)

Lead Sponsor	Collaborator
Riyadh Colleges of Dentistry and Pharmacy

Country where clinical trial is conducted

Saudi Arabia, 

References & Publications (20)

Al Qahtani, Joseph B, Deepthi A, Vijayakumari B, Prevalence of chronic periodontitis and its risk determinants among female patients in the Aseer Region of KSA, Journal of Taibah University Medical Sciences .Volume 12, Issue 3, June 2017, Pages 241-248

Al-Nozha M, Al-Khadra A, Arafah MR, Al-Maatouq MA, Khalil MZ, Khan NB, Al-Mazrou YY, Al-Marzouki K, Al-Harthi SS, Abdullah M, Al-Shahid MS, Al-Mobeireek A, Nouh MS. Metabolic syndrome in Saudi Arabia. Saudi Med J. 2005 Dec;26(12):1918-25. — View Citation

Al-Qurashi FO, Yousef AA, Awary BH. Epidemiological aspects of prematurity in the Eastern region of Saudi Arabia. Saudi Med J. 2016 Apr;37(4):414-9. doi: 10.15537/smj.2016.4.14309. — View Citation

Athyros VG, Ganotakis ES, Elisaf M, Mikhailidis DP. The prevalence of the metabolic syndrome using the National Cholesterol Educational Program and International Diabetes Federation definitions. Curr Med Res Opin. 2005 Aug;21(8):1157-9. — View Citation

Benguigui C, Bongard V, Ruidavets JB, Chamontin B, Sixou M, Ferrières J, Amar J. Metabolic syndrome, insulin resistance, and periodontitis: a cross-sectional study in a middle-aged French population. J Clin Periodontol. 2010 Jul;37(7):601-8. doi: 10.1111/j.1600-051X.2010.01571.x. Epub 2010 May 13. — View Citation

Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012 Jun 9;379(9832):2162-72. doi: 10.1016/S0140-6736(12)60820-4. — View Citation

Dos Prazeres Tavares H, Dos Santos DC, Abbade JF, Negrato CA, de Campos PA, Calderon IM, Rudge MV. Prevalence of metabolic syndrome in non-diabetic, pregnant Angolan women according to four diagnostic criteria and its effects on adverse perinatal outcomes. Diabetol Metab Syndr. 2016 Mar 22;8:27. doi: 10.1186/s13098-016-0139-3. eCollection 2016. — View Citation

Fiorini T, Susin C, da Rocha JM, Weidlich P, Vianna P, Moreira CH, Bogo Chies JA, Rösing CK, Oppermann RV. Effect of nonsurgical periodontal therapy on serum and gingival crevicular fluid cytokine levels during pregnancy and postpartum. J Periodontal Res. 2013 Feb;48(1):126-33. doi: 10.1111/j.1600-0765.2012.01513.x. Epub 2012 Jul 27. — View Citation

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Grundy SM. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):629-36. doi: 10.1161/ATVBAHA.107.151092. Epub 2008 Jan 3. Review. — View Citation

Ide M, Papapanou PN. Epidemiology of association between maternal periodontal disease and adverse pregnancy outcomes--systematic review. J Clin Periodontol. 2013 Apr;40 Suppl 14:S181-94. doi: 10.1111/jcpe.12063. Review. — View Citation

Iheozor-Ejiofor Z, Middleton P, Esposito M, Glenny AM. Treating periodontal disease for preventing adverse birth outcomes in pregnant women. Cochrane Database Syst Rev. 2017 Jun 12;6:CD005297. doi: 10.1002/14651858.CD005297.pub3. Review. — View Citation

International Diabetes Federation. Information on the IDF consensus worldwide definition of the metabolic syndrome. http://www.idf.org/webdata/docs/IDF_Meta_def_final.pdf Accessed 2014 Apr 10.

Knight ET, Liu J, Seymour GJ, Faggion CM Jr, Cullinan MP. Risk factors that may modify the innate and adaptive immune responses in periodontal diseases. Periodontol 2000. 2016 Jun;71(1):22-51. doi: 10.1111/prd.12110. Review. — View Citation

LOE H, SILNESS J. PERIODONTAL DISEASE IN PREGNANCY. I. PREVALENCE AND SEVERITY. Acta Odontol Scand. 1963 Dec;21:533-51. — View Citation

Offenbacher S, Beck JD, Jared HL, Mauriello SM, Mendoza LC, Couper DJ, Stewart DD, Murtha AP, Cochran DL, Dudley DJ, Reddy MS, Geurs NC, Hauth JC; Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators. Effects of periodontal therapy on rate of preterm delivery: a randomized controlled trial. Obstet Gynecol. 2009 Sep;114(3):551-9. doi: 10.1097/AOG.0b013e3181b1341f. — View Citation

Page RC, Eke PI. Case definitions for use in population-based surveillance of periodontitis. J Periodontol. 2007 Jul;78(7 Suppl):1387-99. Review. — View Citation

Penova-Veselinovic B, Keelan JA, Wang CA, Newnham JP, Pennell CE. Changes in inflammatory mediators in gingival crevicular fluid following periodontal disease treatment in pregnancy: relationship to adverse pregnancy outcome. J Reprod Immunol. 2015 Nov;112:1-10. doi: 10.1016/j.jri.2015.05.002. Epub 2015 May 27. — View Citation

Sanz M, D'Aiuto F, Deanfield J, Fernandez-Avilés F. European workshop in periodontal health and cardiovascular disease-scientific evidence on the association between periodontal and cardiovascular diseases: A review of the literature. Eur Heart J Suppl 2010;12 Suppl B:B3-12

SILNESS J, LOE H. PERIODONTAL DISEASE IN PREGNANCY. II. CORRELATION BETWEEN ORAL HYGIENE AND PERIODONTAL CONDTION. Acta Odontol Scand. 1964 Feb;22:121-35. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Periodontal parameters- Change in Gingival Index	Gingival index (GI). All teeth except third molars will be evaluated for gingival in?ammation using a modi?cation of the Loe and Silness , 1963 GI. The GI uses the following scores: 0 = normal gingiva; 1 = mild in?ammation; 2 = moderate in?ammation; and 3 = severe in?ammation. Gingival index will be evaluated at four sites per tooth	• At baseline (before 20 weeks gestation) • 8 weeks after completion of periodontal therapy • Within 1-2 days of delivery
Primary	Periodontal parameters- Change in Plaque Index	Plaque index (PI). Prebrushing plaque scores for the buccal surface of each tooth will be assigned using a zero to three scale (Silness and Loe, 1964 ) PI, with ''0''indicating an absence of plaque on the clinical crown and a ''3'' indicating the presence of soft deposits covering more than two-thirds of the crown.; Plaque index will be evaluated at four sites per tooth	• At baseline (before 20 weeks gestation) • 8 weeks after completion of periodontal therapy • Within 1-2 days of delivery
Primary	Periodontal parameters-Change in Bleeding on probing	Bleeding on probing will be evaluated at six sites per tooth	• At baseline (before 20 weeks gestation) • 8 weeks after completion of periodontal therapy • Within 1-2 days of delivery
Primary	Periodontal parameters- Change in Probing depth (PD)	A manual periodontal probe UNC-15, Hu-Friedy, Chicago, IL ,will be used to record on all teeth present in the mouth. Probing depth will be calculated from gingival margin to base of pocket.; Probing depth will be evaluated at six sites per tooth	• At baseline (before 20 weeks gestation) • 8 weeks after completion of periodontal therapy • Within 1-2 days of delivery
Primary	Periodontal parameters- Change in Clinical attachment level (CAL)	A manual periodontal probe UNC-15, Hu-Friedy, Chicago, IL ,will be used to record on all teeth present in the mouth. CAL will be calculated using the clinically detectable cemento-enamel junction (CEJ) as reference and it will be measured from CEJ to base of pocket.; Clinical attachment level will be evaluated at six sites per tooth	• At baseline (before 20 weeks gestation) • 8 weeks after completion of periodontal therapy • Within 1-2 days of delivery
Secondary	Serum bio markers -Change in Interleukin-6(IL-6)	A 5-ml sample of peripheral venous blood will be collected by vein puncture. The blood samples will be centrifuged at 3000 g for 5 min and the serum will be separated. The serum samples will be frozen in plastic vials at -20ºC until further analyzing. Commercially available ELISA assays will be used to measure concentrations of IL-6 in blood samples, according to the manufacturer's recommendations.	• At baseline (before 20 weeks gestation) • 8 weeks after completion of periodontal therapy • Within 1-2 days of delivery
Secondary	Serum bio markers -Change in Prostaglandin-E2 ( PG-E2)	A 5-ml sample of peripheral venous blood will be collected by vein puncture. The blood samples will be centrifuged at 3000 g for 5 min and the serum will be separated. The serum samples will be frozen in plastic vials at -20ºC until further analyzing. Commercially available ELISA assays will be used to measure concentrations of PGE2 in blood samples, according to the manufacturer's recommendations.	• At baseline (before 20 weeks gestation) • 8 weeks after completion of periodontal therapy • Within 1-2 days of delivery
Secondary	Pregnancy Outcomes -Preterm birth neonate	Preterm birth < 37 weeks neonate taken from patients record	• Within 1-2 days of delivery
Secondary	Pregnancy Outcomes -Low birth weight neonate	Low birth weight < 2500 gms neonate as taken from patients record	• Within 1-2 days of delivery