Human Dental Pulp Mesenchymal Stem Cells for the Treatment of Chronic Periodontitis Patients

A Phase 2, Randomized, Double-blind, Parallel, Placebo-controlled Study to Evaluate Efficacy and Safety of Local Injection of Human Dental Pulp Mesenchymal Stem Cells for the Treatment of Chronic Periodontitis Patients.

The primary objective:To evaluate the efficacy of different administration protocols of human dental pulp mesenchymal stem cells for the treatment of chronic periodontitis patients.

The secondary objective:To evaluate the safety of different administration protocols of human dental pulp mesenchymal stem cells for the treatment of chronic periodontitis patients.

The exploratory objective:To investigate the effects of human dental pulp mesenchymal stem cells on biomarkers in gingival crevicular fluid in chronic periodontitis patients.

Study Overview

• Status: Recruiting
• Conditions: Periodontitis
• Intervention / Treatment: Drug: Human Dental Fulp Stem Cells

Detailed Description

This is a multicenter, randomized, double-blind, parallel, placebo-controlled study, including three treatment groups which are single-dose group, two-dose group (low-dose), and two-dose group (high-dose). The patients of single-dose group will receive only one dose on day 1 (D1), and the patients of two-dose groups will receive one dose on D1 and D90 respectively. 68 participants will be enrolled in each group, and be randomized (3:1) to receive human dental pulp mesenchymal stem cells (hDP-MSCs) or placebo (normal saline). Participants in the single-dose group and the two-dose group (high-dose) will receive local injection of 1.0 × 107 hDP-MSCs (0.6mL normal saline suspension) / periodontal defect site or 0.6mL normal saline / periodontal defect site, and participants in the two-dose group (low-dose) will receive local injection of 1.0 × 106 hDP-MSCs (0.6mL normal saline suspension) / periodontal defect site or 0.6mL normal saline / periodontal defect site. All participants will receive basic periodontal treatment simultaneously.

Dosing interval: the dosing interval is set at 89 days, which is based on the results of preclinical trials of hDP-MSCs, the improvement of periodontitis observed on D90 after hDP-MSCs administration, and good safety profile in phase 1 clinical trial.

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiao Wang, Master; Phone Number: +86 010-82266334; Email: bysykqpeking@126.com

Study Locations

• China
  • Beijng
    • Beijing, Beijng, China, 100191
      • Recruiting
      • Peking University Third Hospital
      • Contact: Meng Wan, doctor; Phone Number: +86 010-82266263; Email: wanmengpeking@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants are eligible to be included in the study only if all of the following criteria apply:

1)18 to 65 years old (including threshold), unlimited gender; 2)Radiological examination of the periodontal defect site shows angular bone defect; 3)The probing depth (PD) at the periodontal defect site is 4 to 8 mm at baseline; 4)Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures; 5)Voluntarily participate in the clinical study, understand and sign the informed consent;

Exclusion Criteria:

• Participants are excluded from the study if any of the following criteria apply:

  1. Participants with severe periodontal diseases (alveolar bone resorption exceeds two-thirds of the tooth root length) which affect the investigator's judgment;
  2. The grade of studied tooth looseness ≥ grade 3 at baseline (only buccolingual movement is defined as grade 1; buccolingual and mesiodistal movement is grade 2; vertical loosening is grade 3);
  3. The studied tooth with occlusal trauma which affect the investigator's judgment;
  4. Participants with surgical treatment of previous periodontal defect sites and adjacent periodontal tissues;
  5. Participants with non-steroid anti-inflammatory drug, steroid hormone therapy, and/or other hormone (except topical hormones) treatment within past 3 months of the screening visit, and/or previous use of bisphosphonates;
  6. Participants with severe systemic infection within past 3 months of the screening visit, or antibiotics treatment within past 72h of the screening visit;
  7. Participants with uncontrolled hypertension within 1 month before screening (defined as sitting systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg after receiving the optimal antihypertensive therapy);
  8. Participants with severe or uncontrolled diseases in any system (cardiac, hepatic, renal, respiratory, hematologic, endocrine, nervous, or psychiatric);
  9. Participants are known to be allergic to any materials that may be used during surgery (allergy-prone constitution or history of allergy to blood products);
  10. Any of the following abnormalities in clinical laboratory tests at screening: ALT > 3 ULN, total bilirubin > 1.5 ULN, serum creatinine > 1.5 ULN, international normalized ratio (INR) ≥ 1.5 ULN or activated partial thromboplastin time (APTT) ≥ 1.5 ULN (except for patients receiving anticoagulation therapy), Hb < 80 g/L, or PLT < 75.0×109/L;
  11. Positive result for any of the following tests at screening: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or Treponema pallidum antibody (TP-Ab);
  12. Females who are pregnant or breastfeeding;
  13. Participants and their partners who plan to conceive or do not agree to use the effective non-pharmacological method of contraceptive during the trial from screening visit to 6 months after the end of the trial;
  14. Participants participated in other clinical studies within past 3 months of the screening visit;
  15. Participants with a history of smoking addiction within past 12 months of the screening visit (the number of cigarettes smoked per day ≥ 10); Other circumstances deemed inappropriate by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single-dose group; Human Dental Fulp Stem Cells Injection: 1X 10^7 cells/periodontaldefect site.	Drug: Human Dental Fulp Stem Cells; Investigational drugs: Based on the initial periodontal treatment (supragingival cleansing, subgingival scaling and root planning), human pulp stem cell injections will be given for a single or two local injection; Other Names: Initial periodontal therapy
Experimental: two-dose group (low-dose); Human Dental Pulp Stem Cells Injection: 1X 10^6 cells/periodontaldefect site. Continuous administration twice, with an interval of 89 days between each administration.	Drug: Human Dental Fulp Stem Cells; Investigational drugs: Based on the initial periodontal treatment (supragingival cleansing, subgingival scaling and root planning), human pulp stem cell injections will be given for a single or two local injection; Other Names: Initial periodontal therapy
Experimental: two-dose group (high-dose); Human Dental Pulp Stem Cells Injection: 1X 10^7 cells/periodontaldefect site. Continuous administration twice, with an interval of 89 days between each administration.	Drug: Human Dental Fulp Stem Cells; Investigational drugs: Based on the initial periodontal treatment (supragingival cleansing, subgingival scaling and root planning), human pulp stem cell injections will be given for a single or two local injection; Other Names: Initial periodontal therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in height of the periodontal bone defect	Changes from baseline in height of the periodontal bone defect which will be examined by CBCT at D90±7 and D180±14 (primary efficacy endpoint)	at baseline, 90 days, 180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in respiration rate of Vital Signs	Respiratory rate, in beats per minute	within 180 days after administration
Changes from baseline in heart rate of Vital Signs	Heart rate in beats per minute	within 180 days after administration
Changes from baseline in blood pressure of Vital Signs	Blood pressure in mmHg, both systolic and diastolic blood pressure will be measured.	within 180 days after administration
Changes from baseline in body temperature of Vital Signs	Body temperature in Celsius degree	within 180 days after administration
Changes from baseline in red blood cell count of Laboratory Examination	Red blood cell count in whole blood is reported in the form of number	within 180 days after administration
Changes from baseline in white blood cell count of Laboratory Examination	White blood cell count in whole blood is reported in the form of number	within 180 days after administration
Changes from baseline in neutrophil count of Laboratory Examination	Neutrophil count in whole blood is reported in the form of number	within 180 days after administration
Changes from baseline in lymphocyte count of Laboratory Examination	Lymphocyte count in whole blood is reported in the form of number	within 180 days after administration
Changes from baseline in platelet count of Laboratory Examination	Platelet count in whole blood is reported in the form of number	within 180 days after administration
Changes from baseline in hemoglobin of Laboratory Examination	Changes of hemoglobin concentration（g/dL）in whole blood will be recorded.	within 180 days after administration
Changes from baseline in PT of Laboratory Examination	Prothrombin time (PT) is a screening test for exogenous coagulation factors	within 180 days after administration
Changes from baseline in INR of Laboratory Examination	International standardized ratio (INR) is calculated from prothrombin time and international sensitivity index (ISI) of the reagent.	within 180 days after administration
Changes from baseline in APTT of Laboratory Examination	Activated partial thromboplastin time (APTT) is a screening test for endogenous coagulation factors	within 180 days after administration
Changes from baseline in total bilirubin of Laboratory Examination	Changes of total bilirubin concentration (μmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in direct bilirubin of Laboratory Examination	Changes of direct bilirubin concentration (μmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in ALT of Laboratory Examination	Changes of ALT concentration (U/L) in serum will be recorded	within 180 days after administration
Changes from baseline in AST of Laboratory Examination	Changes of AST concentration (U/L) in serum will be recorded	within 180 days after administration
Changes from baseline in total protein of Laboratory Examination	Changes of total protein concentration (g/L) in serum will be recorded	within 180 days after administration
Changes from baseline in albumin of Laboratory Examination	Changes of albumin concentration (g/L) in serum will be recorded	within 180 days after administration
Changes from baseline in total bile acid of Laboratory Examination	Changes of total bile acid concentration (μmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in urea of Laboratory Examination	Changes of urea concentration (mmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in creatinine of Laboratory Examination	Changes of creatinine concentration (μmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in uric acid of Laboratory Examination	Changes of uric acid concentration (μmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in glucose of Laboratory Examination	Changes of glucose concentration (mmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in potassium of Laboratory Examination	Changes of potassium concentration (mmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in sodium of Laboratory Examination	Changes of sodium concentration (mmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in chlorine of Laboratory Examination	Changes of chlorine concentration (mmol/L) in serum will be recorded	within 180 days after administration
Changes from baseline in Detection of infectious diseases of Laboratory Examination	It refers to infectious diseases screening	within 180 days after administration
Changes from baseline in IgA of Laboratory Examination	Changes of IgA concentration （g/L）in serum will be recorded	within 180 days after administration
Changes from baseline in IgG of Laboratory Examination	Changes of IgG concentration （g/L）in serum will be recorded	within 180 days after administration
Changes from baseline in IgM of Laboratory Examination	Changes of IgM concentration （g/L）in serum will be recorded	within 180 days after administration
Changes from baseline in total IgE of Laboratory Examination	Changes of total IgE concentration （g/L）in serum will be recorded	within 180 days after administration
Changes from baseline in Pregnancy test of Laboratory Examination	Pregnancy test will be tested in female subjects	within 180 days after administration
Changes from baseline in urine specific gravity of Laboratory Examination	Changes of urine specific gravity will be recorded	within 180 days after administration
Changes from baseline in urine pH of Laboratory Examination	Changes of urine pH value will be recorded	within 180 days after administration
Changes from baseline in urine glucose of Laboratory Examination	Changes of urine glucose will be examined by qualitative test (positive or negative)	within 180 days after administration
Changes from baseline in urine protein of Laboratory Examination	Changes of urine protein will be examined by qualitative test (positive or negative)	within 180 days after administration
Changes from baseline in urine ketone body of Laboratory Examination	Changes of urine ketone body will be examined by qualitative test (positive or negative)	within 180 days after administration
Changes from baseline in urine white blood cell of Laboratory Examination	Changes of white blood cell in urine will be examined by qualitative test (positive or negative)	within 180 days after administration
Changes from baseline in urine bilirubin of Laboratory Examination	Changes of urine bilirubin will be examined by qualitative test (positive or negative)	within 180 days after administration
Changes from baseline in urine occult blood of Laboratory Examination	Changes of urine occult blood will be examined by qualitative test (positive or negative)	within 180 days after administration
Changes from baseline in ECG PR interval	The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.	within 180 days after administration
Changes from baseline in ECG QRS interval	The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.	within 180 days after administration
Changes from baseline in ECG RR interval	The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.	within 180 days after administration
Changes from baseline in ECG QT interval	The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.	within 180 days after administration
Incidence of Treatment-Emergent Adverse Event	Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events during the study period, and the severity of adverse events is determined according to the NCI CTCAE version 5.0	within 180 days after administration
Change from baseline in Clinical Attachment Level (AL)	Clinical Attachment Level (AL) may be assessed to the nearest millimeter by means of a graduated probe and expressed as the distance in millimeters from the CEJ to the bottom of the probeable gingival/periodontal pocket	at baseline, 90 days, 180 days
Change from baseline in Tooth Mobility (TM)	The continuous loss of the supporting tissues during periodontal disease progression may result in increased tooth mobility, which is divided into 3 degree: I°, II°, and III°. Changes from baseline in tooth mobility will be recorded	at baseline, 90 days, 180 days
Change from baseline in Probing Depth (PD)	The probing depth is the distance from the gingival margin to the bottom of the gingival sulcus/pocket, is measured to the nearest millimeter by means of periodontal probe	at baseline, 90 days, 180 days
Change from baseline in Gingival recession （GR）	Exposure of the tooth through apical migration of the gingiva is called gingival recession. Recorded as the distance in millimeters from the CEJ to the gingival margin	at baseline, 90 days, 180 days
Change from baseline in Probing bleeding on probing (BOP)	A periodontal probe is inserted to the "bottom" of the gingival/periodontal pocket applying light force and is moved gently along the tooth (root) surface. If bleeding is provoked by this examination, the site examined is considered bleeding on probing-positive and, hence, inflamed. Probing Bleeding Index is divided into 5 grades: 0, 1, 2, 3 and 4.	at baseline, 90 days, 180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in interleukin-6 (IL-6)	Changes in IL-6 baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720	at baseline, 90 days, 180 days，360 days，720 days
Change from baseline in tumor necrosis factor-alpha (TNF-α)	Changes in TNF-α baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720	at baseline, 90 days, 180 days，360 days，720 days
Change from baseline in matrix metalloproteinase-8 (MMP-8)	Changes in MMP-8 baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720	at baseline, 90 days, 180 days，360 days，720 days
Change from baseline in interleukin-1beta (IL-1β)	Changes in IL-1β baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720	at baseline, 90 days, 180 days，360 days，720 days
Change from baseline in osteoprotegerin (OPG)	Changes in OPG baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720	at baseline, 90 days, 180 days，360 days，720 days
Changes from baseline in height of the periodontal bone defect	Changes from baseline in height of the periodontal bone defect which will be examined by CBCT at D360 and D720	at baseline, 360 days，720 days
Change from baseline in Clinical Attachment Level (AL)	Clinical Attachment Level (AL) may be assessed to the nearest millimeter by means of a graduated probe and expressed as the distance in millimeters from the CEJ to the bottom of the probeable gingival/periodontal pocket	at baseline, 360 days，720 days
Change from baseline in Probing Depth (PD)	The probing depth is the distance from the gingival margin to the bottom of the gingival sulcus/pocket, is measured to the nearest millimeter by means of periodontal probe	at baseline, 360 days，720 days
Change from baseline in Tooth Mobility (TM)	The continuous loss of the supporting tissues during periodontal disease progression may result in increased tooth mobility, which is divided into 3 degree: I°, II°, and III°. Changes from baseline in tooth mobility will be recorded	at baseline, 360 days，720 days
Change from baseline in Gingival recession （GR）	Exposure of the tooth through apical migration of the gingiva is called gingival recession. Recorded as the distance in millimeters from the CEJ to the gingival margin	at baseline, 360 days，720 days
Change from baseline in Probing bleeding on probing (BOP)	A periodontal probe is inserted to the "bottom" of the gingival/periodontal pocket applying light force and is moved gently along the tooth (root) surface. If bleeding is provoked by this examination, the site examined is considered bleeding on probing-positive and, hence, inflamed. Probing Bleeding Index is divided into 5 grades: 0, 1, 2, 3 and 4.	at baseline, 360 days，720 days

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Capital Medical University
• Investigators: Principal Investigator: Xiao Wang, Master, Department of Stomatology, Peking University Third Hospital, Beijing, China

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Estimated): March 7, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 26, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Human Dental Pulp Stem Cell
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Chronic Disease; Periodontitis; Chronic Periodontitis
• Other Study ID Numbers: SH-hDP-MSC-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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