The Safety and Tolerability of Initial Periodontal Therapy Combined With Human Dental Pulp Stem Cell Injection in the Treatment of Chronic Periodontitis

NCT04983225 | Unknown Phase 1

• 1 other identifier: SH-hDP-MSC-101
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The principal objective of this trial is to investigate the safety and tolerability of human dental pulp stem cells injection in the treatment of chronic periodontitis. The secondary objective is to provide the basis for dosage regimen for further clinical trials and to evaluate the preliminary efficacy.

Conditions

Periodontitis

Keywords

Human Dental Pulp Stem Cell

Outcome Measures

Primary Outcomes (49)

• Changes from baseline in respiration rate of Vital Signs.

  Respiration rate in mg(μl)/(h·g)

  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

  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 CPR of Laboratory Examination

  C-reactive protein (CPR) is a phylogenetically highly conserved plasma protein, changes of its plasma concentration（mg/L）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 stool form of Laboratory Examination

  Stool form is classified by Bristol Stool Form Scale into 7 categories scored from 1 to 7; (1) Separate hard lumps like nuts (difficult to pass); (2) Sausage-shaped but lumpy; (3) Like a sausage but with cracks on its surface; (4) Like a sausage or snake, smooth and soft; (5) Soft blobs with clear-cut edges (passed easily); (6) Fluffy pieces with ragged edges, a mushy stool; (7) Watery, no solid pieces, entirely liquid.

  within 180 days after administration.

• Changes from baseline in stool white blood cells of Laboratory Examination

  White blood cell count in stools is reported in the form of number.

  within 180 days after administration.

• Changes from baseline in stool red blood cells of Laboratory Examination

  Red blood cell count in stools is reported in the form of number.

  within 180 days after administration.

• Changes from baseline in stool parasite egg of Laboratory Examination

  Parasite egg count in stools is reported in the form of number.

  within 180 days after administration.

• Changes from baseline in stool OBT of Laboratory Examination

  Changes of stool OBT will be examined by qualitative test (positive or negative).

  within 180 days after administration.

• Changes from baseline in ECG

  The cardiac rhythm is showed in ECG 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.

Secondary Outcomes (7)

• Incidence of Treatment-Emergent Adverse Event

  within 360 days and 720 days after administration

• Change from baseline in Clinical Attachment Level (AL).

  at baseline, 90 days, 180 days ,360 days, 720 days.

• Change from baseline in Probing Depth (PD).

  at baseline, 90 days, 180 days ,360 days, 720 days.

• Change from baseline in Probing Bleeding Index （BI）

  at baseline, 90 days, 180 days ,360 days, 720 days.

• Change from baseline in Gingival recession （GR）

  at baseline, 90 days, 180 days ,360 days, 720 days.

Study Arms (6)

1×10^6 cells/site group

EXPERIMENTAL

Human Dental Pulp Stem Cells Injection: 1×10\^6 cells/periodontal defect site.

Drug: Human Dental Pulp Stem Cells

5×10^6 cells/site group

EXPERIMENTAL

Human Dental Pulp Stem Cells Injection: 5×10\^6 cells/periodontal defect site.

Drug: Human Dental Pulp Stem Cells

1×10^7 cells/site group

EXPERIMENTAL

Human Dental Pulp Stem Cells Injection: 1×10\^7 cells/periodontal defect site.

Drug: Human Dental Pulp Stem Cells

2×10^7 cells/two sites group

EXPERIMENTAL

Human Dental Pulp Stem Cells Injection: 1×10\^7 cells/periodontal defect site, two locations in total, and the total cell injection volume is 2 × 10\^7 cells/2 periodontal defect sites.

Drug: Human Dental Pulp Stem Cells

3~4×10^7 cells/three or four sites group

EXPERIMENTAL

Human Dental Pulp Stem Cells Injection: 1×10\^7 cells/periodontal defect site, three or four locations in total, and the total cell injection volume is 3 × 10\^7 to 4 × 10\^7 cells/3 to 4 periodontal defect sites.

Drug: Human Dental Pulp Stem Cells

Saline solution group

PLACEBO COMPARATOR

Saline solution: 0.6mL/periodontal defect site.

Other: Saline solution

Interventions

Human Dental Pulp Stem Cells DRUG

Investigational drugs: based on initial periodontal therapy (supragingival cleansing, subgingival scaling and root planning), human dental pulp stem cell injection will be given for a single local injection;

Also known as: Initial periodontal therapy

1×10^6 cells/site group; 1×10^7 cells/site group; 2×10^7 cells/two sites group; 3~4×10^7 cells/three or four sites group; 5×10^6 cells/site group

Saline solution OTHER

Blank control: initial Basal periodontal therapy (supragingival cleansing, subgingival scaling and root planning) followed by a single local injection of normal saline.

Also known as: Initial periodontal therapy

Saline solution group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 years old (including threshold ), unlimited gender.
• Radiological examination of the periodontal defect site shows vertical bone defect, and the probing depth (PD) is 4 to 8 mm.
• Voluntarily participate in the clinical study, understand and sign the informed consent, and comply with the relevant regulations during the study period and within 18 months after the end of the study.

You may not qualify if:

• Subjects with severe periodontal diseases (alveolar bone resorption generally exceeds two-thirds of the tooth root length) and affects the study tooth judgment;
• The grade of studied tooth looseness ≥ grade 2 (only buccolingual movement is defined as grade 1; buccolingual and mesiodistal movement is grade 2; vertical loosening is grade 3);
• Subjects with surgical treatment of previous periodontal bone defect sites and adjacent periodontal tissues;
• Subjects with non-steroid anti-inflammatory drug, steroid hormone therapy, and/or hormone (except topical hormones) treatment, bisphosphonates within the previous 3 months before screening;
• Subjects with severe systemic infection within the previous 3 months before screening; or antibiotics treatment within 72 h before screening;
• Subjects with uncontrolled hypertension within 1 month before screening (defined as sitting systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg after receiving the optimal antihypertensive therapy);
• Subjects with systemic diseases (including but not limited to: malignant tumor or with positive tumor examination during screening, diabetes, heart failure caused by heart disease, myocardial infarction within the first 6 months before screening, angina symptoms within the first 6 months before screening, and congenital heart disease, etc.);
• Subjects who are known to be allergic to any of the materials used in the treatment;
• Subjects with the allergic constitution and previous history of allergy to blood products;
• Laboratory test (any of them meets): abnormal liver function: ALT \> 80 U/L or AST \> 70 U/L; abnormal renal function: serum creatinine (picric acid method) \> 97 μmol/L;
• Subjects with a bleeding tendency or coagulant dysfunction (INR ≥ 1.5 × ULN, or APTT ≥ 1.5 × ULN (except the ones who are receiving anticoagulant therapy)) or serious hematologic diseases (such as grade 3 or above anemia (Hb \< 80 g/L); grade 2 or above thrombocytopenia ( \< 75.0 × 109 /L))
• Viral serology positive (HBsAg, HCV antibody, HIV antibody, treponema pallidum antibody) positive;
• Subjects with unprotected sex within the previous 1 month before the screening;
• Pregnant or lactating women, or subjects with a positive result of β-HCG before the screening, or subjects who are unable or unwilling to take contraceptive measures under the investigator instruction;
• Women with oral contraceptives;

Sponsors & Collaborators

• Peking University Third Hospital: lead
• Capital Medical University: collaborator

Study Sites (1)

Peking University Third Hospital

Beijing, Beijng, 100191, China

Location

MeSH Terms

Conditions

Periodontitis

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Xiao Wang, Master

  Department of Stomatology, Peking University Third Hospital, Beijing, China.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 30, 2021
• Study Start: July 31, 2021
• Primary Completion: July 31, 2024
• Study Completion: August 31, 2024
• Last Updated: May 31, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)