human dental pulp mesenchymal stem cells for the treatment of chronic periodontitis patients

Conditions: Periodontitis

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.

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.

Eligibility 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: 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.

Keywords: human dental pulp stem cell