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

Effectiveness and Safety of Method of Maxilla Alveolar Process Reconstruction Using Tissue Engineered Construction Based on a Synthetic Tricalcium Phosphate and Autologous Multipotent Mesenchymal Stromal Cells Obtained From Oral Mucosa

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 121359
    • 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, 127473
    • A.I. Evdokimov Moscow State Medical Stomatological University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tissue engineered construction implantation	Procedure: Oral mucosa biopsy; Procedure: Sinus lift with implantation of tissue engineered construction; Device: Dental implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of serious adverse events (SAEs) and serious adverse reactions (SARs)	1 week after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life monitoring	Quality of life estimated by validated questionnaire: the Short Form (36) Health Survey (SF-36).	up to 24 weeks after treatment
Changes in bone tissue volume	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)	up to 24 weeks after treatment
Correlation of morphometrical analysis using cone beam CT scan with absolute value of the newly formed bone	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.	24 weeks after treatment

Collaborators and Investigators

• Sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation
• Investigators: Principal Investigator: Ilya I Eremin, MD, PhD, 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; Principal Investigator: Grigory Volozhin A Volozhin, MD, PhD, A.I. Evdokimov Moscow State Medical Stomatological University

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: August 4, 2014
• First Submitted That Met QC Criteria: August 4, 2014
• First Posted (Estimate): August 5, 2014

Study Record Updates

• Last Update Posted (Estimate): November 30, 2016
• Last Update Submitted That Met QC Criteria: November 29, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Dental Implantation; Oral Mucosa; Alveolar Bone Loss; Alveolar Bone Atrophy; Bone Tissue Reconstruction; Sinus Lift; Autologous Multipotent Mesenchymal Stem Cell; Autologous MMSCs; Synthetic Tricalcium Phosphate; Tissue Engineered Construction
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Pathological Conditions, Anatomical; Bone Diseases; Periodontal Atrophy; Bone Resorption; Atrophy; Alveolar Bone Loss
• Other Study ID Numbers: RU-CCH-06-01-14