Comparative evaluation of bone grafting using rhBMP-2 versus autogenous bone graft in patients with cleft lip and palate

ISRCTN	ISRCTN28401658
DOI	https://doi.org/10.1186/ISRCTN28401658
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	Nil known
Sponsor	Damascus University
Funder	Damascus University

Submission date: 26/05/2025
Registration date: 27/05/2025
Last edited: 27/05/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Oral Health

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Secondary alveolar bone grafting is an important surgical procedure used to repair the alveolar cleft in patients with cleft lip and palate. This procedure helps to restore the bone in the affected area, improving dental stability and facial structure. The study aims to compare the effectiveness of using human bone morphogenetic protein-2 (BMP-2) versus traditional autogenous bone grafts for secondary alveolar bone grafting, focusing on bone volume formation, healing outcomes, and patient satisfaction.

Who can participate?
Children aged 8 to 11 years with complete unilateral alveolar cleft type (A), class III, who are classified as ASA I or II and have good oral hygiene. Participation requires written informed consent from the legal guardian.

What does the study involve?
Eligible participants will undergo secondary alveolar bone grafting. Patients will be randomly assigned to receive either BMP-2 treatment or an autogenous bone graft. The volume of newly formed bone will be measured using multi-slice computed tomography (MSCT) before surgery and six months after. Healing, complications, and patient satisfaction will be monitored at regular intervals up to six months post-surgery.

What are the possible benefits and risks of participating?
Participants may benefit from improved bone formation and facial function. Risks include potential surgical complications and mild postoperative discomfort. All procedures will be performed under general anesthesia by experienced surgeons, and patients will be closely monitored during recovery.

Where is the study run from?
National Hospital and Children’s Hospital, Mazzeh Highway, Damascus, Syria.

When is the study starting and how long is it expected to run for?
January 2023 to January 2025

Who is funding the study?
Damascus University, Syria.

Who is the main contact?
Dr. Khaled Zain
kaledzain156@gmail.com

Contact information

Dr Kaled Zain
Public, Scientific, Principal investigator

Kafr-sosah
Damascus
-
Syria

Phone	+963 (0)947480875
Email	kaledzain156@gmail.com

Study information

Primary study design	Interventional
Study design	Interventional randomized controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomized clinical trial to evaluate secondary alveolar bone grafting using recombinant human bone morphogenetic protein-2 (rhBMP-2) versus autogenous bone in patients with unilateral cleft lip and palate
Study objectives	We hypothesize that secondary alveolar bone grafting using rhBMP-2 provides comparable or superior clinical and radiographic outcomes compared to autogenous bone grafts in patients with unilateral cleft lip and palate.
Ethics approval(s)	Approved 01/02/2023, Biomedical Research Ethical Committee of Damascus University (Al-mazeh, Damascus, -, Syria; +963 (0)113341864; manager@hcsr.gov.sy), ref: 22749
Health condition(s) or problem(s) studied	Cleft lip and palate
Intervention	Informed consent will be obtained from all participants prior to enrollment. Eligible patients with unilateral cleft lip and palate will be clinically and radiographically assessed to ensure they meet the inclusion criteria. Each participant will be randomly assigned to one of two treatment groups using a computer-generated randomization sequence. On the day of surgery, all procedures will be performed under general anesthesia following standard preoperative protocols. In the autogenous graft group, alveolar bone grafting will be performed using particulate cancellous bone harvested from the anterior iliac crest. In the rhBMP-2 group, bone grafting will be performed using an absorbable collagen sponge (ACS) impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2), placed within the alveolar cleft defect. All surgical procedures will be performed by the same surgical team to ensure standardization. Postoperative care, including antibiotics, analgesics, and oral hygiene instructions, will be standardized across both groups.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	The volume of newly formed bone within the alveolar cleft, assessed using multislice computed tomography (MSCT). Preoperative cleft volume will be calculated from the initial MSCT scans. Six months postoperatively, the residual defect volume will be measured using the same imaging modality. The volume of newly formed bone will be determined by subtracting the postoperative residual cleft volume from the preoperative cleft volume. This volumetric analysis will be performed using specialized radiographic software to ensure precise measurement and consistency.
Key secondary outcome measure(s)	1. Radiographic Bone Density Assessment Radiographic bone density of the newly formed bone will be measured six months postoperatively using multislice computed tomography (MSCT). Measurements will be limited to the internal portion of the grafted defect, excluding adjacent cortical bone. Hounsfield Units (HU) will be used as the measurement scale. Five consecutive 1-mm-thick axial slices will be analyzed, and the mean of these five slices will represent the final bone density value. 2. Fistula Presence Evaluation The presence or absence of postoperative oronasal fistula will be assessed clinically and through patient inquiry at 10 days, 1 month, and 6 months after surgery. 3. Bone Graft Healing Complications Complications related to bone graft healing will be evaluated using the Sanz-Martin criteria one month postoperatively. Parameters include wound dehiscence and presence or absence of infection. 4. Soft Tissue Healing Early soft tissue healing will be assessed weekly during the first postoperative month using the Early Healing Index (EHI). 5. Postoperative Edema Postoperative facial edema will be evaluated using the Chaudhary edema scoring system on days 3, 5, and 7 following surgery. 6.Hospital Stay Duration The number of days each patient remains hospitalized postoperatively will be recorded for both groups. 7. Patient Satisfaction with the Surgical Procedure One month postoperatively, patient satisfaction regarding the surgical procedure itself will be assessed using a visual analog scale (VAS) ranging from 0 to 100. 8. Patient Satisfaction with the Outcome Six months postoperatively, patient satisfaction with the treatment outcome will be evaluated using a visual analog scale (VAS) ranging from 0 to 100. 9. Periodontal Assessment of Adjacent Teeth 9.1. Probing Depth: Measured at six sites around each tooth adjacent to the alveolar cleft using a UNC-15 periodontal probe, preoperatively and at 3 months postoperatively. 9.2. Bleeding on Probing: Recorded as positive (+) or negative (−) within 15–20 seconds after probing at the same six sites, both before surgery and three months after. 9.3. Width of Keratinized Tissue: Measured at the mid-buccal surface from the gingival margin to the mucogingival junction using the periodontal probe, both before surgery and at 3 months postoperatively.
Completion date	05/01/2025

Eligibility

Participant type(s)	Healthy volunteer
Age group	Child
Lower age limit	8 Years
Upper age limit	11 Years
Sex	All
Target sample size at registration	14
Key inclusion criteria	1. Patients with complete unilateral alveolar clefts of type (A), class III according to the LAHS classification, requiring secondary alveolar bone grafting. This type represents an alveolar cleft extending to the nasal floor. 2. Age between 8 and 11 years. 3. Classified as ASA physical status I or II. 4. Good oral hygiene, defined as a plaque index not exceeding 40% based on O’Leary's index. 5. Written informed consent obtained from the patient's legal guardian after full explanation of the study purpose and procedures.
Key exclusion criteria	1. Presence of bilateral clefts, or cleft lip without involvement of the palate. 2. Presence of additional craniofacial abnormalities or congenital syndromes. 3. Patients with systemic conditions that contraindicate general anesthesia or may impair wound and bone healing (ASA class III or IV). 4. History of previous infection at the alveolar cleft site. 5. Patients who have undergone prior secondary alveolar bone grafting. 6. Refusal of participation by the child or legal guardian.
Date of first enrolment	01/06/2023
Date of final enrolment	01/09/2024

Locations

Countries of recruitment

Syria

Study participating centre

National Hospital and Children's Hospital

Mazzeh Highway
Damascus
0100
Syria

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The data to be shared will include summarized statistical results derived from individual participant data. These data will be made accessible following the publication of the study findings. Informed consent for data sharing will be obtained from all participants or their legal guardians. All shared data will be completely anonymized to ensure participant confidentiality. There are no ethical or legal barriers restricting the sharing of these data

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

27/05/2025: Trial's existence confirmed by Damascus University.