Prognostic Biomarkers for Pulpotomy Outcome

Discovering Prognostic Biomarkers for Pulpotomy Outcome in Permanent Mature Teeth With Irreversible Pulpitis

This study will recruit 180 molars diagnosed with irreversible pulpitis. Full pulpotomy will be performed on 120 teeth, while RCT (root canal treatment) will be conducted on another cohort of 60 teeth as the control for assessing long-term outcomes. Additionally, 12 blood samples and pulp tissues from healthy teeth receiving elective RCT will be collected as the controls. The first pulpal blood sample will be collected after caries removal and pulp exposure. Subsequently, the entire coronal pulp tissue will be removed and collected for histological examination, image-based spatial and scRNA-seq analyses. A second pulpal blood sample will be collected from the radicular pulp tissue. Both blood samples will be used to profile the inflammation-related biomarkers through multiplex immunoassays. The remaining pulp tissue will be covered by Biodentine and restored with resin-based composite. Pulpotomy treatment outcomes will be evaluated clinically and radiographically at 6 and 12 months. The biomarkers identified in the pulpal blood and histology and the single-cell transcriptomes of the coronal pulp will be compared with the treatment "success" and "failure" groups upon one year. The outcome of RCT will be compared with that of full pulpotomy at 24 months.

Study Overview

• Status: Recruiting
• Conditions: Pulpitis - Irreversible
• Intervention / Treatment: Procedure: Full pulpotomy; Procedure: Root canal treatment

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rong Cen; Phone Number: +852 28590290; Email: cenrong@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Clinical Research Centre, Faculty of Dentistry, The University of Hong Kong
    • Contact: Rong Cen; Phone Number: +852 28590290

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Permanent molars showing clinical and radiographic evidence of a deep carious lesion (extend to the three-quarters thickness of dentine radiographically) extending close to the pulp chamber
• Clinical diagnosis of irreversible pulpitis, including spontaneous pain, lingering pain with cold stimulation, no or mild tenderness to percussion, normal apical tissue or widening of the periodontal ligament space but with no signs of periapical periodontitis (i.e., PAI score 1 or 2)
• Positive response to cold and electric pulp test.

Exclusion Criteria:

• Tooth with no response to the cold and electric tests, presence of apical radiolucency (greater than periodontal widening), signs of canal calcification and resorption, history of trauma, unrestorable or nonfunctional teeth, and evidence of perio-endo lesion
• Intraoperative bleeding time is more than 10 minutes or less than 10 μL pulpal blood can be obtained
• Patients with a compromised immune status (such as HIV or organ transplant) or with any history of taking analgesics/antibiotics in the past one week.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Root canal treatment	Procedure: Root canal treatment; The regular procedure of root canal treatment will be performed on teeth with irreversible pulpitis
Active Comparator: Full pulpotomy	Procedure: Full pulpotomy; A full pulpotomy will be performed by removing the entire roof of the pulp chamber and the remaining pulp tissue will be covered by Biodentine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate	Success rate of full pulpotomy and RCT in teeth with irreversible pulpitis	2 years
Biomarkers	Quantitative descriptive analysis of the expression of biomarkers commonly found in tissue inflammation using multiplex immunoassay (Millipore, USA). The kits include targets as follows: sCD40L;EGF;Eotaxin;FGF-2;Flt-3 ligand;Fractalkine;G-CSF;GM-CSF;GROα;IFNα2;IFNγ;IL-1α;IL-1β;IL-1ra;IL-2;IL-3;IL-4;IL-5;IL-6;IL-7;IL-8;IL-9;IL-10;IL-12 (p40);IL-12 (p70);IL-13;IL-15;IL-17A;IL-17E/IL-25;IL-17F;IL-18;IL-22;IL-27;IP-10;MCP-1;MCP-3;M-CSF;MDC (CCL22);MIG;MIP-1α;MIP-1β;PDGF-AA;PDGF-AB/BB;RANTES;TGFα;TNFα;TNFβ;VEGF-A; MMP-1, -2, -7, -9, -10.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation	Correlation of biomarkers' expression to the outcome of full pulpotomy in teeth with irreversible pulpitis to identify objective prognostic biomarkers for full pulpotomy; biomarkers to investigate are described in Outcome 2	2 years

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Chengfei Zhang, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: July 20, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 20, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Dental Pulp Diseases; Pulpitis
• Other Study ID Numbers: UW 23-133

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No