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

Study Overview
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Brief Summary
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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.

Official Title
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Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair

Conditions
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Cleft Lip and Palate

Intervention / Treatment
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* Combination Product: Mesenchymal stem cells associated with biomaterials
* Combination Product: Iliac crest autogenous bone graft


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cells associated with biomaterials<br>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<br>* Deciduous dental pulp mesenchymal stem cells associated with hydroxyapatita/collagen.<br>|
| Active Comparator: Iliac crest autogenous bone graft<br>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<br>* Autogenous bone will be obtained from iliac crest.<br>|

What is the study measuring?
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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 |