Effectiveness and Safety of Method of Maxilla Alveolar Process Reconstruction Using Synthetic Tricalcium Phosphate and Autologous MMSCs

Phase 1

• Conditions: Alveolar Bone Atrophy; Alveolar Bone Loss; Partially Edentulous Maxilla
• Interventions: Procedure: Oral mucosa biopsy; Procedure: Sinus lift with implantation of tissue engineered construction; Device: Dental implant

• Registration Number: NCT02209311
• Lead Sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation

Brief Summary

Autologous MMSCs will be isolated from oral mucosa biopsy sample and expanded in vitro.Tissue engineered construction will be created using synthetic tricalcium phosphate and autologous MMSCs. Patients will undergo sinus lift procedure with implantation of created tissue-engineered construction. This is a single arm study with no control. All patients receive cell therapy.

Detailed Description

Patients with verified diagnosis partially edentulous maxilla and alveolar bone atrophy will undergo oral mucosa biopsy and autologous MMSCs will be derived and expanded in vitro during 3-4 weeks. After that tissue engineered construction will be created using synthetic tricalcium phosphate and autologous MMSCs. Patients will undergo sinus lift procedure with implantation of created tissue-engineered construction. Six months later patients will undergo dental implant installation. Biopsy of bone tissue at the site of sinus lift will be performed as a part of dental implant installation with subsequent histological analysis of bone specimen.

Study Timeline

• Study First Submitted: 2014-08-04
• Study First Submitted QC: 2014-08-04
• Study First Posted: 2014-08-05
• Study Start: 2014-09
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-29
• Last Update Posted: 2016-11-30
• Primary Completion: 2017-10
• Study Completion: 2018-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Partially edentulous maxilla
• Height of the bone tissue in the area of reconstruction 1 - 5 mm according to results of cone-beam computed tomography
• Minimal height of the augmentation - 8 mm
• Volume of bone tissue deficiency of the alveolar process of the maxilla 3 - 5 cm3
• Implant installation scheduled to be at least 6 months after sinus-lift operation
• Patient is familiar with Participant information sheet
• Patient signed informed consent form

Non-inclusion Criteria:

• Chronic and acute ear, nose and throat diseases, including maxillary sinusitis, foreign bodies in the maxillary sinus, odontogenic and not odontogenic maxillary sinus cyst
• Medical history of surgery on maxillary sinuses during preceding 6 months prior to implantation of tissue engineered construction
• Progressive somatic disease (clinically significant diseases of the cardiovascular, hematopoietic or endocrine system, systemic diseases, immunopathological states)
• Patients with malignant tumors including postoperative period, patients receiving chemotherapy and/or radiotherapy
• Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and alcohol abuse etc.)
• Significant weight loss (> 10% of body weight in the previous year) of unknown etiology
• Patient prescribed for any medications with proven effect on bone metabolism
• Diabetes mellitus, disorders of thyroid and parathyroid glands
• Clinically significant abnormalities in results of laboratory tests
• Participation in other clinical trials (or administration of investigational drugs) during 3 months prior inclusion

Exclusion Criteria

• Patient's refusal from the further participation in trial
• Patient's refusal from compliance with the requirements of contraception during the participation in research
• Plaque index (PI)> 15%
• Sulcus bleeding index (SBI) > 10%
• Chronic kidney disease IV - V stages (creatinine clearance < 30 mL/min estimated by Cockroft-Gault formula)
• Confirmed syphilis, HIV, hepatitis B or C infections

Dropout Criteria:

• Perforation of the Schneider's membrane more than 5 mm on the stage of the sinus-lift operation
• Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tissue engineered construction implantation	Sinus lift with implantation of tissue engineered construction	-
Tissue engineered construction implantation	Dental implant	-
Tissue engineered construction implantation	Oral mucosa biopsy	-

Primary Outcome Measures

Name	Time	Method
Number of serious adverse events (SAEs) and serious adverse reactions (SARs)	1 week after treatment

Secondary Outcome Measures

Name	Time	Method
Changes in bone tissue volume	up to 24 weeks after treatment	Changes in volume and density of bone tissue at the site of manipulation and newly formed bone micro-architecture assessed by cone beam CT (morphometrical analysis using Hounsfield unit measurements)
Correlation of morphometrical analysis using cone beam CT scan with absolute value of the newly formed bone	24 weeks after treatment	Biopsy of bone tissue at the site of sinus lift will be performed as a part of dental implant installation. Bone sample will be evaluated histologically: absolute value of the newly formed bone will be calculated using histomorphometrical analysis.
Quality of life monitoring	up to 24 weeks after treatment	Quality of life estimated by validated questionnaire: the Short Form (36) Health Survey (SF-36).

Trial Locations

Locations (2)

Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation; Center for Biomedical Technologies; 🇷🇺 Moscow, Russian Federation

A.I. Evdokimov Moscow State Medical Stomatological University; 🇷🇺 Moscow, Russian Federation