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

Tracking Information

• First Submitted Date: November 29, 2018
• First Posted Date: December 6, 2018
• Last Update Posted Date: May 13, 2020
• Actual Study Start Date: April 5, 2019
• Actual Primary Completion Date: December 6, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 4, 2018)

• 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.
• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 1, 2019)

• Non serious adverse events [ Time Frame: 15 days; 3, 6 and 12 months ]
  Frequency of participants experiencing at least one non serious adverse event
• Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair [ Time Frame: Bone tissue engineering ]
• 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
• 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.
• 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.
• 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)

Original Secondary Outcome Measures (submitted: December 4, 2018)

• Non serious adverse events [ Time Frame: 15 days; 3, 6 and 12 months ]
  Frequency of participants experiencing at least one non serious adverse event
• Health-related quality of life [ Time Frame: 6 and 12 months ]
  Health-related quality of life measured by the Youth Quality of Life Facial Differences - YQOL-FD. It consists of 56 item both contextual (i.e., can be reported by others) and perceptual (i.e., known only to the youth themselves). The YQOL scores are transformed to a 0-100 scale and higher scores indicating better QoL. (continuous outcome, maesured by: mean)
• 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
• 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.
• 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.
• Patient-reported outcome (PRO, including appearance, fuction and quality of life) [ Time Frame: 6 and 12 months ]
  Assessed by CLEFT-Q, a self-report PRO instrument, tool answered independently by 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)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
• Official Title: Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cleft Lip and Palate

Intervention

• Combination Product: Mesenchymal stem cells associated with biomaterials
  Deciduous dental pulp mesenchymal stem cells associated with hydroxyapatita/collagen.
• Combination Product: Iliac crest autogenous bone graft
  Autogenous bone will be obtained from iliac crest.

Study Arms

• 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).
  Intervention: Combination Product: Mesenchymal stem cells associated with biomaterials
• 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.
  Intervention: Combination Product: Iliac crest autogenous bone graft

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 4, 2018): 62
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 15, 2019
• Actual Primary Completion Date: December 6, 2019 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 12 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT03766217
• Other Study ID Numbers: CAAE47719215.5.0000.5461
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Daniela Franco Bueno, Hospital Sirio-Libanes
• Original Responsible Party: Same as current
• Current Study Sponsor: Hospital Sirio-Libanes
• Original Study Sponsor: Same as current
• Collaborators: Ministry of Health, Brazil
• Investigators: Not Provided
• PRS Account: Hospital Sirio-Libanes
• Verification Date: May 2020