Clinical trial NCT04983225: The Safety and Tolerability of Initial Periodontal Therapy Combined With Human Dental Pulp Stem Cell Injection in the Treatment of Chronic Periodontitis
Official title: A Randomized, Double-blind, Blank Controlled, Dose-escalation Clinical Trial to Evaluate the Safety and Tolerability of Initial Periodontal Therapy Combined With Human Dental Pulp Stem Cell Injection in the Treatment of Chronic Periodontitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Periodontitis
Keywords: Human Dental Pulp Stem Cell
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Capital Medical University
First posted: 2021-07-30
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Initial periodontal therapy involves cleaning, scaling and root planing. The present dose-escalating, randomized, double-blind, blank controlled clinical trial will be conducted to evaluate the safety and tolerability of dental pulp mesenchymal stem cells injection as an adjunct with Initial periodontal therapy in chronic periodontitis. Patients meeting the inclusion criteria will be assigned into five dose groups, in a 3:1 ratio within each group to treat with drug or placebo after initial periodontal therapy. The evaluation will be conducted based on safety and efficacy end points.

Eligibility criteria: Inclusion Criteria:

* 18 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.

Exclusion Criteria:

* 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;
* Subjects with a history of smoking addiction in the previous 12 months before the screening (the number of cigarettes smoked per day ≥ 10);
* Subjects with mental or conscious disorders;
* Subjects who participated in other clinical studies within 3 months before the screening;
* Other circumstances deemed inappropriate by the investigator.

Primary outcomes:
measure: Changes from baseline in respiration rate of Vital Signs.
timeFrame: within 180 days after administration.
measure: Changes from baseline in heart rate of Vital Signs.
timeFrame: within 180 days after administration.
measure: Changes from baseline in blood pressure of Vital Signs.
timeFrame: within 180 days after administration.
measure: Changes from baseline in body temperature of Vital Signs.
timeFrame: within 180 days after administration.
measure: Changes from baseline in red blood cell count of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in white blood cell count of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in neutrophil count of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in lymphocyte count of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in platelet count of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in hemoglobin of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in PT of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in INR of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in APTT of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in total bilirubin of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in direct bilirubin of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in ALT of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in AST of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in total protein of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in albumin of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in total bile acid of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urea of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in creatinine of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in uric acid of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in glucose of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in potassium of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in sodium of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in chlorine of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in CPR of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in Detection of infectious diseases of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in IgA of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in IgG of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in IgM of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in total IgE of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in Pregnancy test of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine specific gravity of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine pH of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine glucose of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine protein of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine ketone body of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine white blood cell of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine bilirubin of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in urine occult blood of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in stool form of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in stool white blood cells of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in stool red blood cells of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in stool parasite egg of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in stool OBT of Laboratory Examination
timeFrame: within 180 days after administration.
measure: Changes from baseline in ECG
timeFrame: within 180 days after administration.
measure: Incidence of Treatment-Emergent Adverse Event
timeFrame: within 180 days after administration.
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Event
timeFrame: within 360 days and 720 days after administration
measure: Change from baseline in Clinical Attachment Level (AL).
timeFrame: at baseline, 90 days, 180 days ,360 days, 720 days.
measure: Change from baseline in Probing Depth (PD).
timeFrame: at baseline, 90 days, 180 days ,360 days, 720 days.
measure: Change from baseline in Probing Bleeding Index （BI）
timeFrame: at baseline, 90 days, 180 days ,360 days, 720 days.
measure: Change from baseline in Gingival recession （GR）
timeFrame: at baseline, 90 days, 180 days ,360 days, 720 days.
measure: Change from baseline in Tooth Mobility (TM).
timeFrame: at baseline, 90 days, 180 days ,360 days, 720 days.
measure: Changes from baseline in height of the periodontal bone defect and average density of alveolar ridge.
timeFrame: at baseline, 90 days, 180 days ,360 days, 720 days.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijng
Study officials:
affiliation: Department of Stomatology, Peking University Third Hospital, Beijing, China.
name: Xiao Wang, Master
role: PRINCIPAL_INVESTIGATOR
References: