Endo-perio Disease - Treatment Outcomes Using Conventional and Hydraulic Calcium Silicate Sealer With or Without LPRF

Endodontic-periodontal Disease - Comparison of Treatment Outcome Using Conventional and Hydraulic Calcium Silicate Sealer With or Without LPRF and Characterisation of Host-microbiome Interaction

The endodontic periodontal-disease is characterized by the involvement of the pulp and periodontal disease in the same tooth. The anatomic connections between the dental pulp and the periodontium provide a pathway for perio-endo communication via apical foramina, lateral canals, exposed dentinal tubules, and developmental grooves. These pathways provide an egress for pulpal disease to affect the periodontium and conversely, an ingress for periodontal disease to affect the pulp.

Teeth with endo-perio disease, which are deemed salvageable might require root canal (endodontic) treatment, followed by staged periodontal treatment. Compared to conventional sealers used for endodontic treatment, the hydraulic calcium silicate based sealers (HCSB)s have excellent sealing ability, biocompatibility, regeneration ability, and antimicrobial characteristics. However little is known about its clinical benefits when used to treat endo-perio disease.

The gold standard treatment for periodontitis affected teeth associated with intrabony lesions is guided tissue regeneration (GTR) which has significant improved clinical outcomes over open flap debridement (Cochrane systematic review 2005). However, the success the of this regenerative technique requires careful case and defect selection. We propose the use of an autologous bioactive scaffold, leukocyte platelet rich fibrin (L-PRF) to achieve regeneration of periodontal soft and hard tissues, resulting in faster healing, greater bone infill and improved predictability of clinical outcomes

Study Overview

• Status: Not yet recruiting
• Conditions: Periodontitis; Endodontic Disease
• Intervention / Treatment: Procedure: Experimental: RCT using hydraulic calcium silicate sealer and L-PRF + GTR; Procedure: Experimental: RCT using conventional sealer and L-PRF + GTR; Procedure: Experimental: RCT using hydraulic calcium silicate sealer and GTR; Procedure: Active Comparator: RCT using conventional sealer and GTR (bone substitute + collagen membrane)

Detailed Description

Primary periodontal /secondary endodontic lesions and true combined lesions is challenging since the outcome of these is significantly less predictable than that of those arising due to primary endo disease and require multidisciplinary management involving endodontic treatment in the form of root canal treatment followed by staged periodontal treatment.

This includes initial non-surgical periodontal therapy to reduce the microbiologic burden in the periodontal pocket. After a 3-to-6 month period following the completion of endodontic treatment, the apical healing is evaluated and the periodontal condition reassessed and then the decision is made for periodontal regenerative therapies to promote the formation of new cementum, periodontal ligament, and bone to achieve esthetic and hygienic goals. These regenerative therapies include tissue engineering techniques, such as guided tissue regeneration (GTR); implantation of enamel protein matrix derivatives; application of signalling molecules, such as growth factors, and leucocyte- platelet rich fibrin (L-PRF). Without concomitant regenerative procedures, success ranges from 27% to 37%. When regenerative procedures are added to endodontic therapy, the chance of a successful outcome improves to 77.5%.

L-PRF is obtained through the centrifugation of blood resulting in a strong fibrin matrix enriched with platelets and growth factors. Previous evidence suggest that this can be successfully used in the treatment of intrabony defects, but no randomised controlled trial has been conducted examining the additional benefits of L-PRF when used in conjunction with GTR in the treatment of intrabony defects associated with endodontic-periodontal disease.

The investigators have previously also investigated the microbiome of endodontic infections using targeted 16SrRNA gene and house-keeping gene sequence analysis, we determined the predominant cultivable microbiota of primary and secondary (failed) Endodontic infections. The investigators have lately investigated the microbiome of root canal infections using next generation sequencing targeting region V1-V2 of 16SrRNA gene (unpublished data). The investigators are also currently investigating the host microbiome interactions in these conditions. Although Endodontic periodontal disease differ in pathogenicity but they do share common microbial factors and inflammatory mediators.

• Study Type: Interventional
• Enrollment (Anticipated): 115
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sadia Niazi; Phone Number: +44 (0) 2071887459; Email: sadia.niazi@kcl.ac.uk
• Study Contact Backup: Name: Emily Lu; Email: emily.lu@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust
    • Contact: Emily Lu; Email: emily.lu@kcl.ac.uk
    • Contact: Sadia Niazi; Email: sadia.niazi@kcl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Diagnosis of Endodontic-periodontal disease without root damage in periodontitis patients, Grades I, II, III according to Herrera 2017 classification.

  • Presence of ≥ 1 intrabony defect: interproximal probing pocket depth ≥ 5 mm and ≥ 3mm radiographic intrabony defect, adjacent to single rooted and multi-rooted teeth associated with endodontic-periodontal disease
  • Age: 18-80
  • Non-smokers (zero cigarettes within last 5 years)

Exclusion Criteria:

• Endodontic considerations: severely sclerosed canals, external cervical resorption and internal root resorption, perforations, root fracture or cracking, re- RCT, apical surgery and unrestorable teeth

• Teeth with defects not amenable to regeneration or molar teeth planned for root resection

  - Periodontal treatment carried out previously to the study site within the last 12 months (excluding not-extensive subgingival debridement as judged by the examining clinician),

• presence of drug induced gingival overgrowth.
• Smoking (current or in past 5 years) including e-cigarettes/ vaping
• History of alcohol or drug abuse,
• Systemic antibiotic therapy during the 3 months preceding the baseline exam,
• History of conditions requiring prophylactic antibiotic coverage prior to invasive dental procedures,
• Anti-inflammatory or anticoagulant therapy during the month preceding the baseline exam,
• Medical history of diabetes or transmittable diseases,
• Chronic inflammatory conditions: chronic peptic ulcer, tuberculosis, rheumatoid arthritis, ulcerative colitis, crohn's disease, active hepatitis, inflammatory bowel diseases, irritable bowel syndrome, autoimmune diseases, liver diseases, renal diseases or cancer
• Medications which alter bone metabolism: hormone replacement therapy, immunosuppressive drugs, corticosteroids, selective serotonin reuptake inhibitors, tumour necrosis factor blockers, IV bisphosphonates, and/or antiresorptive drugs,
• Self-reported pregnancy or lactation
• Surgical procedures in the last 6months (any type of surgical procedures)
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that according to the investigator may increase the risk associated with trial participation,
• Poor compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RCT using hydraulic calcium silicate sealer and L-PRF + GTR; Endodontic-periodontal disease patients undergoing root canal treatment using hydraulic calcium silicate sealer and L-PRF + GTR (bone substitute + collagen membrane)	Procedure: Experimental: RCT using hydraulic calcium silicate sealer and L-PRF + GTR; Endodontic treatment with hydraulic calcium silicate sealer, followed by periodontal surgery using GTR +/- LPRF
Experimental: RCT using conventional sealer and L-PRF + GTR; Endodontic-periodontal disease patients undergoing root canal treatment using conventional sealer and L-PRF + GTR (bone substitute + collagen membrane)	Procedure: Experimental: RCT using conventional sealer and L-PRF + GTR; Endodontic treatment with conventional sealer followed by periodontal treatment with PRF + GTR
Experimental: RCT using hydraulic calcium silicate sealer and GTR; Endodontic-periodontal disease patients undergoing root canal treatment using hydraulic calcium silicate sealer and GTR (bone substitute + collagen membrane)	Procedure: Experimental: RCT using hydraulic calcium silicate sealer and GTR; Endodontic treatment with hydraulic calcium silicate sealer, followed by periodontal surgery using GTR only
Active Comparator: RCT using conventional sealer and GTR (bone substitute + collagen membrane); Endodontic-periodontal disease patients undergoing root canal treatment using conventional sealer and GTR (bone substitute + collagen membrane) This is our control group Both the endodontic and periodontal lesions are managed using gold standard of care biomaterials and techniques	Procedure: Active Comparator: RCT using conventional sealer and GTR (bone substitute + collagen membrane); Endodontic treatment with conventional sealer followed by periodontal treatment with GTR only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probing pocket depth change in mm	Probing pocket depth change in mm at 12months (T8); at 18months (T9)	at 12months (T8); at 18months (T9)
Clinical attachment level (CAL) change in mm	Clinical attachment level (CAL) change in mm at 12months (T8); at 18months (T9)	at 12months (T8); at 18months (T9)
Change in the size of the lesion/ intrabony defect using Cone Beam CT and PA radiographs.	Change in the size of the lesion/ intrabony defect using Cone Beam CT and PA at 12months (T8); at 18months (T9)	at 12months (T8); at 18months (T9)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in levels of inflammatory markers and growth factors in blood, saliva and GCF (T1, T2, T3, T5, T7, T8, T9)	Changes in levels of inflammatory markers and growth factors in blood, saliva and GCF (T1, T2, T3, T5, T7, T8, T9)	baseline (T1), Endodontic treatment, within 4 weeks from baseline (T2), Review at 3months (T3), Review at 6 months (T5), Review at 9 months (T7), Review at 12months( T8), Review at 18months (T9)
Plaque, Salivary and root canal microbiome associated with presence and healing of intrabony defects (T1, T2, T3, T5, T7, T8, T9)	Plaque, Salivary and root canal samples for microbiome analysis	baseline (T1), Endodontic treatment, within 4 weeks from baseline (T2), Review at 3months (T3), Review at 6 months (T5), Review at 9 months (T7), Review at 12months( T8), Review at 18months (T9)
Expression of inflammatory mediators from granulation tissue derived from periodontal intrabony defects (T6)	Expression of inflammatory mediators from granulation tissue derived from periodontal intrabony defects (T6)	Surgical periodontal treatment, within 6-8 months from endodontic treatment (T6)
Patient reported outcome measures (PROMs)	This will be measured using standardised questionnaire, the Oral Health Impact Profile short form (OHIP-14)	baseline (T1), Endodonic treatment, within 4 weeks from baseline (T2), Review at 3months (T3), Review at 6 months (T5), Review at 9 months (T7), Review at 12months( T8), Review at 18months (T9)

Collaborators and Investigators

• Sponsor: King's College London
• Investigators: Principal Investigator: Sadia Niazi, King's College London, London SE1 9RT

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): May 1, 2027
• Study Completion (Anticipated): May 1, 2033

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 12, 2023

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Endo-perio lesions
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Tooth Diseases; Periodontitis; Dental Pulp Diseases; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Calcium, Dietary
• Other Study ID Numbers: EDGE 147667

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The research data will only be accessed by PIs, or CIs involved in the research project. The PhD student and statistician will only have access to anonymised data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No