Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair (CLOSE)

Iliac crest autogenous bone graft is accepted as the most effective method for secondary alveolar cleft repair. However this method is associated with complications. As an alternative, mesenchymal stem cells associated with biomaterials have been used for the rehabilitation of the alveolar bone cleft of patients with cleft lip and palate. This is a RCT comparing mesenchymal stem cells obtained from autogenous deciduous dental pulp associated with biomaterials versus iliac crest autogenous bone graft for secondary alveolar cleft repair.

Study Overview

• Status: Completed
• Conditions: Cleft Lip and Palate
• Intervention / Treatment: Combination product: Mesenchymal stem cells associated with biomaterials; Combination product: Iliac crest autogenous bone graft

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01308-050
    • Hospital Sirio-Libanes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• non syndromic unilateral cleft lip and palate;
• age between 7 and 12 years;
• to have the jaw aligned and ready to receive the graft.

Exclusion Criteria:

• previous surgery to correct the alveolar cleft;
• have the canine erupted before grafting;
• incomplete orthodontic treatment;
• incomplete CT scan documentation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal stem cells associated with biomaterials; Mesenchymal stem cells obtained from autogenous deciduous dental pulp associated with biomaterials. The stem cells will be obtained by enzimatic digestion in GMP laboratory and will be seed into the biomaterial (hydroxyapatite/collagen).	Combination product: Mesenchymal stem cells associated with biomaterials; Deciduous dental pulp mesenchymal stem cells associated with hydroxyapatita/collagen.
Active Comparator: Iliac crest autogenous bone graft; Autogenous bone will be obtained from iliac crest. The prepare of the receptor area will be the same in both arms and will follow current recommendations.	Combination product: Iliac crest autogenous bone graft; Autogenous bone will be obtained from iliac crest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alveolar bone filling rate	Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.	12 months
Serious adverse events	Serious adverse events resulting in death, life-threatening event, hospitalization, prolongation of existing hospitalization (for > 24 hours), persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon medical judgment, it may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Frequency of participants experiencing at least one serious adverse event.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non serious adverse events	Frequency of participants experiencing at least one non serious adverse event	15 days; 3, 6 and 12 months
Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair		Bone tissue engineering
Position of the canine tooth and formation of dental root	Position of the canine tooth and formation of dental root assessed by CT scan	12 months
Alveolar bone filling rate	Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.	6 months
Serious adverse events	Serious adverse events resulting in death, life-threatening event, hospitalization, prolongation of existing hospitalization (for > 24 hours), persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon medical judgment, it may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Frequency of participants experiencing at least one serious adverse event.	15 days; 3 and 6 months
Patient-reported outcome (PRO, including appearance, fuction and quality of life)	Assessed by CLEFT-Q, a self-report PRO instrument, tool answered independently patients themselves, without interpretation by the parent(s) or healthcare provider. The CLEFT-Q consists of 13 independently functioning domains (171 items) measuring appearance, facial function and quality of life. Each domain is composed of a series of items that together evaluate a unidimensional construct. A higher score means a better result (continuous outcome, measured by: mean)	pre surgery and 12 months

Collaborators and Investigators

• Sponsor: Hospital Sirio-Libanes
• Collaborators: Ministry of Health, Brazil

Publications and helpful links

General Publications

• Tanikawa DYS, Pinheiro CCG, Almeida MCA, Oliveira CRGCM, Coudry RA, Rocha DL, Bueno DF. Deciduous Dental Pulp Stem Cells for Maxillary Alveolar Reconstruction in Cleft Lip and Palate Patients. Stem Cells Int. 2020 Mar 12;2020:6234167. doi: 10.1155/2020/6234167. eCollection 2020.
• Pinheiro CCG, Leyendecker Junior A, Tanikawa DYS, Ferreira JRM, Jarrahy R, Bueno DF. Is There a Noninvasive Source of MSCs Isolated with GMP Methods with Better Osteogenic Potential? Stem Cells Int. 2019 Nov 6;2019:7951696. doi: 10.1155/2019/7951696. eCollection 2019.

Helpful Links

• First results published
• "in vitro" results

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2019
• Primary Completion (Actual): December 6, 2019
• Study Completion (Actual): December 15, 2019

Study Registration Dates

• First Submitted: November 29, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 13, 2020
• Last Update Submitted That Met QC Criteria: May 11, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities; Stomatognathic Diseases; Mouth Diseases; Lip Diseases; Mouth Abnormalities; Stomatognathic System Abnormalities; Cleft Lip
• Other Study ID Numbers: CAAE47719215.5.0000.5461

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No