Clinical trial NCT05924373: Human Dental Pulp Mesenchymal Stem Cells for the Treatment of Chronic Periodontitis Patients
Official title: A Phase 2, Randomized, Double-blind, Parallel, Placebo-controlled Study to Evaluate Efficacy and Safety of Local Injection of Human Dental Pulp Mesenchymal Stem Cells for the Treatment of Chronic Periodontitis Patients.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Periodontitis
Keywords: Human Dental Pulp Stem Cell
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Capital Medical University
First posted: 2023-06-29
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, randomized, double-blind, parallel, placebo-controlled study
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Changes from baseline in height of the periodontal bone defect
timeFrame: at baseline, 90 days, 180 days
Secondary 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 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 ECG PR interval
timeFrame: within 180 days after administration
measure: Changes from baseline in ECG QRS interval
timeFrame: within 180 days after administration
measure: Changes from baseline in ECG RR interval
timeFrame: within 180 days after administration
measure: Changes from baseline in ECG QT interval
timeFrame: within 180 days after administration
measure: Incidence of Treatment-Emergent Adverse Event
timeFrame: within 180 days after administration
measure: Change from baseline in Clinical Attachment Level (AL)
timeFrame: at baseline, 90 days, 180 days
measure: Change from baseline in Tooth Mobility (TM)
timeFrame: at baseline, 90 days, 180 days
measure: Change from baseline in Probing Depth (PD)
timeFrame: at baseline, 90 days, 180 days
measure: Change from baseline in Gingival recession （GR）
timeFrame: at baseline, 90 days, 180 days
measure: Change from baseline in Probing bleeding on probing (BOP)
timeFrame: at baseline, 90 days, 180 days
Other outcomes:
measure: Change from baseline in interleukin-6 (IL-6)
timeFrame: at baseline, 90 days, 180 days，360 days，720 days
measure: Change from baseline in tumor necrosis factor-alpha (TNF-α)
timeFrame: at baseline, 90 days, 180 days，360 days，720 days
measure: Change from baseline in matrix metalloproteinase-8 (MMP-8)
timeFrame: at baseline, 90 days, 180 days，360 days，720 days
measure: Change from baseline in interleukin-1beta (IL-1β)
timeFrame: at baseline, 90 days, 180 days，360 days，720 days
measure: Change from baseline in osteoprotegerin (OPG)
timeFrame: at baseline, 90 days, 180 days，360 days，720 days
measure: Changes from baseline in height of the periodontal bone defect
timeFrame: at baseline, 360 days，720 days
measure: Change from baseline in Clinical Attachment Level (AL)
timeFrame: at baseline, 360 days，720 days
measure: Change from baseline in Probing Depth (PD)
timeFrame: at baseline, 360 days，720 days
measure: Change from baseline in Tooth Mobility (TM)
timeFrame: at baseline, 360 days，720 days
measure: Change from baseline in Gingival recession （GR）
timeFrame: at baseline, 360 days，720 days
measure: Change from baseline in Probing bleeding on probing (BOP)
timeFrame: at baseline, 360 days，720 days
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: