Human Dental Pulp Mesenchymal Stem Cells for the Treatment of Chronic Periodontitis Patients
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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:
|
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- Changes from baseline in height of the periodontal bone defect [at baseline, 90 days, 180 days]
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)
Secondary Outcome Measures
- Changes from baseline in respiration rate of Vital Signs [within 180 days after administration]
Respiratory rate, in beats per minute
- Changes from baseline in heart rate of Vital Signs [within 180 days after administration]
Heart rate in beats per minute
- Changes from baseline in blood pressure of Vital Signs [within 180 days after administration]
Blood pressure in mmHg, both systolic and diastolic blood pressure will be measured.
- Changes from baseline in body temperature of Vital Signs [within 180 days after administration]
Body temperature in Celsius degree
- Changes from baseline in red blood cell count of Laboratory Examination [within 180 days after administration]
Red blood cell count in whole blood is reported in the form of number
- Changes from baseline in white blood cell count of Laboratory Examination [within 180 days after administration]
White blood cell count in whole blood is reported in the form of number
- Changes from baseline in neutrophil count of Laboratory Examination [within 180 days after administration]
Neutrophil count in whole blood is reported in the form of number
- Changes from baseline in lymphocyte count of Laboratory Examination [within 180 days after administration]
Lymphocyte count in whole blood is reported in the form of number
- Changes from baseline in platelet count of Laboratory Examination [within 180 days after administration]
Platelet count in whole blood is reported in the form of number
- Changes from baseline in hemoglobin of Laboratory Examination [within 180 days after administration]
Changes of hemoglobin concentration（g/dL）in whole blood will be recorded.
- Changes from baseline in PT of Laboratory Examination [within 180 days after administration]
Prothrombin time (PT) is a screening test for exogenous coagulation factors
- Changes from baseline in INR of Laboratory Examination [within 180 days after administration]
International standardized ratio (INR) is calculated from prothrombin time and international sensitivity index (ISI) of the reagent.
- Changes from baseline in APTT of Laboratory Examination [within 180 days after administration]
Activated partial thromboplastin time (APTT) is a screening test for endogenous coagulation factors
- Changes from baseline in total bilirubin of Laboratory Examination [within 180 days after administration]
Changes of total bilirubin concentration (μmol/L) in serum will be recorded
- Changes from baseline in direct bilirubin of Laboratory Examination [within 180 days after administration]
Changes of direct bilirubin concentration (μmol/L) in serum will be recorded
- Changes from baseline in ALT of Laboratory Examination [within 180 days after administration]
Changes of ALT concentration (U/L) in serum will be recorded
- Changes from baseline in AST of Laboratory Examination [within 180 days after administration]
Changes of AST concentration (U/L) in serum will be recorded
- Changes from baseline in total protein of Laboratory Examination [within 180 days after administration]
Changes of total protein concentration (g/L) in serum will be recorded
- Changes from baseline in albumin of Laboratory Examination [within 180 days after administration]
Changes of albumin concentration (g/L) in serum will be recorded
- Changes from baseline in total bile acid of Laboratory Examination [within 180 days after administration]
Changes of total bile acid concentration (μmol/L) in serum will be recorded
- Changes from baseline in urea of Laboratory Examination [within 180 days after administration]
Changes of urea concentration (mmol/L) in serum will be recorded
- Changes from baseline in creatinine of Laboratory Examination [within 180 days after administration]
Changes of creatinine concentration (μmol/L) in serum will be recorded
- Changes from baseline in uric acid of Laboratory Examination [within 180 days after administration]
Changes of uric acid concentration (μmol/L) in serum will be recorded
- Changes from baseline in glucose of Laboratory Examination [within 180 days after administration]
Changes of glucose concentration (mmol/L) in serum will be recorded
- Changes from baseline in potassium of Laboratory Examination [within 180 days after administration]
Changes of potassium concentration (mmol/L) in serum will be recorded
- Changes from baseline in sodium of Laboratory Examination [within 180 days after administration]
Changes of sodium concentration (mmol/L) in serum will be recorded
- Changes from baseline in chlorine of Laboratory Examination [within 180 days after administration]
Changes of chlorine concentration (mmol/L) in serum will be recorded
- Changes from baseline in Detection of infectious diseases of Laboratory Examination [within 180 days after administration]
It refers to infectious diseases screening
- Changes from baseline in IgA of Laboratory Examination [within 180 days after administration]
Changes of IgA concentration （g/L）in serum will be recorded
- Changes from baseline in IgG of Laboratory Examination [within 180 days after administration]
Changes of IgG concentration （g/L）in serum will be recorded
- Changes from baseline in IgM of Laboratory Examination [within 180 days after administration]
Changes of IgM concentration （g/L）in serum will be recorded
- Changes from baseline in total IgE of Laboratory Examination [within 180 days after administration]
Changes of total IgE concentration （g/L）in serum will be recorded
- Changes from baseline in Pregnancy test of Laboratory Examination [within 180 days after administration]
Pregnancy test will be tested in female subjects
- Changes from baseline in urine specific gravity of Laboratory Examination [within 180 days after administration]
Changes of urine specific gravity will be recorded
- Changes from baseline in urine pH of Laboratory Examination [within 180 days after administration]
Changes of urine pH value will be recorded
- Changes from baseline in urine glucose of Laboratory Examination [within 180 days after administration]
Changes of urine glucose will be examined by qualitative test (positive or negative)
- Changes from baseline in urine protein of Laboratory Examination [within 180 days after administration]
Changes of urine protein will be examined by qualitative test (positive or negative)
- Changes from baseline in urine ketone body of Laboratory Examination [within 180 days after administration]
Changes of urine ketone body will be examined by qualitative test (positive or negative)
- Changes from baseline in urine white blood cell of Laboratory Examination [within 180 days after administration]
Changes of white blood cell in urine will be examined by qualitative test (positive or negative)
- Changes from baseline in urine bilirubin of Laboratory Examination [within 180 days after administration]
Changes of urine bilirubin will be examined by qualitative test (positive or negative)
- Changes from baseline in urine occult blood of Laboratory Examination [within 180 days after administration]
Changes of urine occult blood will be examined by qualitative test (positive or negative)
- Changes from baseline in ECG PR interval [within 180 days after administration]
The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.
- Changes from baseline in ECG QRS interval [within 180 days after administration]
The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.
- Changes from baseline in ECG RR interval [within 180 days after administration]
The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.
- Changes from baseline in ECG QT interval [within 180 days after administration]
The cardiac rhythm is showed in 12 Leads Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded.
- Incidence of Treatment-Emergent Adverse Event [within 180 days after administration]
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
- Change from baseline in Clinical Attachment Level (AL) [at baseline, 90 days, 180 days]
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
- Change from baseline in Tooth Mobility (TM) [at baseline, 90 days, 180 days]
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
- Change from baseline in Probing Depth (PD) [at baseline, 90 days, 180 days]
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
- Change from baseline in Gingival recession （GR） [at baseline, 90 days, 180 days]
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
- Change from baseline in Probing bleeding on probing (BOP) [at baseline, 90 days, 180 days]
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.
Other Outcome Measures
- Change from baseline in interleukin-6 (IL-6) [at baseline, 90 days, 180 days，360 days，720 days]
Changes in IL-6 baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720
- Change from baseline in tumor necrosis factor-alpha (TNF-α) [at baseline, 90 days, 180 days，360 days，720 days]
Changes in TNF-α baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720
- Change from baseline in matrix metalloproteinase-8 (MMP-8) [at baseline, 90 days, 180 days，360 days，720 days]
Changes in MMP-8 baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720
- Change from baseline in interleukin-1beta (IL-1β) [at baseline, 90 days, 180 days，360 days，720 days]
Changes in IL-1β baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720
- Change from baseline in osteoprotegerin (OPG) [at baseline, 90 days, 180 days，360 days，720 days]
Changes in OPG baseline will be confirmed through gingival crevicular fluid detection at D90 D180 D360 and D720
- Changes from baseline in height of the periodontal bone defect [at baseline, 360 days，720 days]
Changes from baseline in height of the periodontal bone defect which will be examined by CBCT at D360 and D720
- Change from baseline in Clinical Attachment Level (AL) [at baseline, 360 days，720 days]
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
- Change from baseline in Probing Depth (PD) [at baseline, 360 days，720 days]
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
- Change from baseline in Tooth Mobility (TM) [at baseline, 360 days，720 days]
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
- Change from baseline in Gingival recession （GR） [at baseline, 360 days，720 days]
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
- Change from baseline in Probing bleeding on probing (BOP) [at baseline, 360 days，720 days]
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.
Eligibility Criteria
Criteria
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:
-
Participants with severe periodontal diseases (alveolar bone resorption exceeds two-thirds of the tooth root length) which affect the investigator's judgment;
-
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);
-
The studied tooth with occlusal trauma which affect the investigator's judgment;
-
Participants with surgical treatment of previous periodontal defect sites and adjacent periodontal tissues;
-
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;
-
Participants with severe systemic infection within past 3 months of the screening visit, or antibiotics treatment within past 72h of the screening visit;
-
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);
-
Participants with severe or uncontrolled diseases in any system (cardiac, hepatic, renal, respiratory, hematologic, endocrine, nervous, or psychiatric);
-
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);
-
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;
-
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);
-
Females who are pregnant or breastfeeding;
-
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;
-
Participants participated in other clinical studies within past 3 months of the screening visit;
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University Third Hospital | Beijing | Beijng | China | 100191 |
Sponsors and Collaborators
- Peking University Third Hospital
- Capital Medical University
Investigators
- Principal Investigator: Xiao Wang, Master, Department of Stomatology, Peking University Third Hospital, Beijing, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SH-hDP-MSC-102