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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Changes from baseline in heart rate of Vital Signs.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
1×10^6 cells/site group
Human Dental Pulp Stem Cells Injection: 1×10^6 cells/periodontal defect site.
干预措施: Human Dental Pulp Stem Cells (Drug)
5×10^6 cells/site group
Human Dental Pulp Stem Cells Injection: 5×10^6 cells/periodontal defect site.
干预措施: Human Dental Pulp Stem Cells (Drug)
1×10^7 cells/site group
Human Dental Pulp Stem Cells Injection: 1×10^7 cells/periodontal defect site.
干预措施: Human Dental Pulp Stem Cells (Drug)
2×10^7 cells/two sites group
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.
干预措施: Human Dental Pulp Stem Cells (Drug)
3~4×10^7 cells/three or four sites group
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.
干预措施: Human Dental Pulp Stem Cells (Drug)
Saline solution group
Saline solution: 0.6mL/periodontal defect site.
干预措施: Saline solution (Other)
结局指标
主要结局
Changes from baseline in heart rate of Vital Signs.
时间窗: within 180 days after administration.
Heart rate in beats per minute
Changes from baseline in blood pressure of Vital Signs.
时间窗: within 180 days after administration.
Blood pressure in mmHg
Changes from baseline in red blood cell count of Laboratory Examination
时间窗: within 180 days after administration.
Red blood cell count in whole blood is reported in the form of number.
Changes from baseline in neutrophil count of Laboratory Examination
时间窗: within 180 days after administration.
Neutrophil count in whole blood is reported in the form of number.
Changes from baseline in total bilirubin of Laboratory Examination
时间窗: within 180 days after administration.
Changes of total bilirubin concentration (μmol/L) in serum will be recorded.
Changes from baseline in white blood cell count of Laboratory Examination
时间窗: within 180 days after administration.
White blood cell count in whole blood is reported in the form of number.
Changes from baseline in lymphocyte count of Laboratory Examination
时间窗: within 180 days after administration.
Lymphocyte count in whole blood is reported in the form of number.
Changes from baseline in body temperature of Vital Signs.
时间窗: within 180 days after administration.
Body temperature in Celsius degree
Changes from baseline in total bile acid of Laboratory Examination
时间窗: within 180 days after administration.
Changes of total bile acid concentration (μmol/L) in serum will be recorded.
Changes from baseline in respiration rate of Vital Signs.
时间窗: within 180 days after administration.
Respiration rate in mg(μl)/(h·g)
Changes from baseline in platelet count of Laboratory Examination
时间窗: 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
时间窗: 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
时间窗: within 180 days after administration.
Prothrombin time (PT) is a screening test for exogenous coagulation factors.
Changes from baseline in INR of Laboratory Examination
时间窗: 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 urea of Laboratory Examination
时间窗: within 180 days after administration.
Changes of urea concentration (mmol/L) in serum will be recorded.
Changes from baseline in sodium of Laboratory Examination
时间窗: within 180 days after administration.
Changes of sodium concentration (mmol/L) in serum will be recorded.
Changes from baseline in chlorine of Laboratory Examination
时间窗: within 180 days after administration.
Changes of chlorine concentration (mmol/L) in serum will be recorded.
Changes from baseline in APTT of Laboratory Examination
时间窗: within 180 days after administration.
Activated partial thromboplastin time (APTT) is a screening test for endogenous coagulation factors.
Changes from baseline in ALT of Laboratory Examination
时间窗: within 180 days after administration.
Changes of ALT concentration (U/L) in serum will be recorded.
Changes from baseline in AST of Laboratory Examination
时间窗: within 180 days after administration.
Changes of AST concentration (U/L) in serum will be recorded.
Changes from baseline in albumin of Laboratory Examination
时间窗: within 180 days after administration.
Changes of albumin concentration (g/L) in serum will be recorded.
Changes from baseline in uric acid of Laboratory Examination
时间窗: 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
时间窗: within 180 days after administration.
Changes of glucose concentration (mmol/L) in serum will be recorded.
Changes from baseline in potassium of Laboratory Examination
时间窗: within 180 days after administration.
Changes of potassium concentration (mmol/L) in serum will be recorded.
Changes from baseline in CPR of Laboratory Examination
时间窗: within 180 days after administration.
C-reactive protein (CPR) is a phylogenetically highly conserved plasma protein, changes of its plasma concentration（mg/L）will be recorded.
Changes from baseline in Detection of infectious diseases of Laboratory Examination
时间窗: within 180 days after administration.
It refers to infectious diseases screening.
Changes from baseline in IgA of Laboratory Examination
时间窗: within 180 days after administration.
Changes of IgA concentration （g/L）in serum will be recorded.
Changes from baseline in IgG of Laboratory Examination
时间窗: within 180 days after administration.
Changes of IgG concentration （g/L）in serum will be recorded.
Changes from baseline in IgM of Laboratory Examination
时间窗: within 180 days after administration.
Changes of IgM concentration （g/L）in serum will be recorded.
Changes from baseline in direct bilirubin of Laboratory Examination
时间窗: within 180 days after administration.
Changes of direct bilirubin concentration (μmol/L) in serum will be recorded.
Changes from baseline in urine protein of Laboratory Examination
时间窗: within 180 days after administration.
Changes of urine protein will be examined by qualitative test (positive or negative).
Changes from baseline in urine occult blood of Laboratory Examination
时间窗: within 180 days after administration.
Changes of urine occult blood will be examined by qualitative test (positive or negative).
Changes from baseline in stool white blood cells of Laboratory Examination
时间窗: within 180 days after administration.
White blood cell count in stools is reported in the form of number.
Changes from baseline in stool OBT of Laboratory Examination
时间窗: within 180 days after administration.
Changes of stool OBT will be examined by qualitative test (positive or negative).
Changes from baseline in total protein of Laboratory Examination
时间窗: within 180 days after administration.
Changes of total protein concentration (g/L) in serum will be recorded.
Changes from baseline in creatinine of Laboratory Examination
时间窗: within 180 days after administration.
Changes of creatinine concentration (μmol/L) in serum will be recorded.
Changes from baseline in urine ketone body of Laboratory Examination
时间窗: 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
时间窗: 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
时间窗: within 180 days after administration.
Changes of urine bilirubin will be examined by qualitative test (positive or negative).
Changes from baseline in stool parasite egg of Laboratory Examination
时间窗: within 180 days after administration.
Parasite egg count in stools is reported in the form of number.
Changes from baseline in urine glucose of Laboratory Examination
时间窗: within 180 days after administration.
Changes of urine glucose will be examined by qualitative test (positive or negative).
Changes from baseline in total IgE of Laboratory Examination
时间窗: 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
时间窗: within 180 days after administration.
Pregnancy test will be tested in female subjects
Changes from baseline in urine specific gravity of Laboratory Examination
时间窗: within 180 days after administration.
Changes of urine specific gravity will be recorded.
Changes from baseline in urine pH of Laboratory Examination
时间窗: within 180 days after administration.
Changes of urine pH value will be recorded.
Changes from baseline in stool red blood cells of Laboratory Examination
时间窗: within 180 days after administration.
Red blood cell count in stools is reported in the form of number.
Changes from baseline in stool form of Laboratory Examination
时间窗: within 180 days after administration.
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.
Changes from baseline in ECG
时间窗: within 180 days after administration.
The cardiac rhythm is showed in ECG in the form of continuous curve. Changes of this continuous curve will be recorded.
Incidence of Treatment-Emergent Adverse Event
时间窗: 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.
次要结局
- Changes from baseline in height of the periodontal bone defect and average density of alveolar ridge.(at baseline, 90 days, 180 days ,360 days, 720 days.)
- 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 Gingival recession （GR）(at baseline, 90 days, 180 days ,360 days, 720 days.)
- Change from baseline in Tooth Mobility (TM).(at baseline, 90 days, 180 days ,360 days, 720 days.)
- Incidence of Treatment-Emergent Adverse Event(within 360 days and 720 days after administration)
- Change from baseline in Probing Bleeding Index （BI）(at baseline, 90 days, 180 days ,360 days, 720 days.)