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

• ClinicalTrials.gov Identifier: NCT03766217
• Recruitment Status: Completed
• First Posted: December 6, 2018
• Last Update Posted: May 13, 2020
• Sponsor: Hospital Sirio-Libanes
• Collaborator: Ministry of Health, Brazil
• Information provided by (Responsible Party): Daniela Franco Bueno, Hospital Sirio-Libanes

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cleft Lip and Palate	Combination Product: Mesenchymal stem cells associated with biomaterials; Combination Product: Iliac crest autogenous bone graft	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
• Actual Study Start Date: April 5, 2019
• Actual Primary Completion Date: December 6, 2019
• Actual Study Completion Date: December 15, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Alveolar bone filling rate [ Time Frame: 12 months ]
   Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.
2. Serious adverse events [ Time Frame: 12 months ]

   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.

Secondary Outcome Measures :

1. Non serious adverse events [ Time Frame: 15 days; 3, 6 and 12 months ]
   Frequency of participants experiencing at least one non serious adverse event
2. Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair [ Time Frame: Bone tissue engineering ]
3. Position of the canine tooth and formation of dental root [ Time Frame: 12 months ]
   Position of the canine tooth and formation of dental root assessed by CT scan
4. Alveolar bone filling rate [ Time Frame: 6 months ]
   Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.
5. Serious adverse events [ Time Frame: 15 days; 3 and 6 months ]

   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.

6. Patient-reported outcome (PRO, including appearance, fuction and quality of life) [ Time Frame: pre surgery and 12 months ]
   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)

Eligibility Criteria

• Ages Eligible for Study: 7 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Brazil

Hospital Sírio-Libanes

São Paulo, Brazil, 01308-050

Sponsors and Collaborators

Hospital Sirio-Libanes

Ministry of Health, Brazil

More Information

Additional Information:

First results published 

"in vitro" results 

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.

• Responsible Party: Daniela Franco Bueno, Principal Investigator, Hospital Sirio-Libanes
• ClinicalTrials.gov Identifier: NCT03766217
• Other Study ID Numbers: CAAE47719215.5.0000.5461
• First Posted: December 6, 2018
• Last Update Posted: May 13, 2020
• Last Verified: May 2020

• 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

Additional relevant MeSH terms:

Cleft Lip; Lip Diseases; Mouth Diseases; Stomatognathic Diseases; Mouth Abnormalities; Stomatognathic System Abnormalities; Congenital Abnormalities