Bone Grafting for Cleft Lip and Palate

Overseen By Yvette Boyd

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: No CLP, Failed repair, Syndromic CLP, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether an alternative bone grafting method using special proteins and materials (DBM/BMP) can be more cost-effective and cause less pain than the traditional method using a person's own bone (ICBG) for treating cleft lip and palate. Researchers aim to determine if this new method can reduce surgery time while achieving similar bone healing. Individuals with a cleft lip and palate, a clear bone gap in the mouth, and orthodontic clearance for surgery might be suitable candidates for this trial. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for these treatments?

Research has shown that treatments using Bone Morphogenic Protein (BMP) and Demineralized Bone Matrix (DBM) have been well-tolerated in past studies. For example, one study on recombinant human BMP-2 (a type of BMP used in bone reconstruction) found it safe for surgeries on the jaw and face. Additionally, early results indicate that DBM effectively supports bone growth, suggesting it works well in bone grafting.

Regarding side effects, the data is promising. Improvements in bone density and height were observed a few months after surgery in groups treated with rhBMP-2, with no major safety concerns reported. This suggests the treatment is generally safe for humans.

Since this trial is in a late phase, the treatment has already undergone several tests for safety and effectiveness. This provides some reassurance about its safety. However, as with any medical treatment, individual experiences can vary, so discussing potential risks with healthcare professionals is always important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the intervention using DBM/BMP for bone grafting in cleft lip and palate patients because it introduces a novel approach compared to the standard method of using the patient's own iliac crest bone graft (ICBG). Unlike ICBG, which requires harvesting bone from the patient's hip, DBM (Demineralized Bone Matrix) combined with BMP (Bone Morphogenetic Protein) is a synthetic option that promotes bone growth. This method could reduce the need for additional surgery to harvest bone, potentially leading to less pain and quicker recovery for patients. Additionally, BMP actively stimulates bone formation, offering a promising alternative that might improve the effectiveness of the grafting process.

What evidence suggests that this trial's treatments could be effective for Cleft Lip and Palate?

Research has shown that using Demineralized Bone Matrix (DBM) with Bone Morphogenic Protein (BMP) for bone grafting in the jaw can be effective. In this trial, some participants will receive the DBM/BMP treatment. Studies have found that DBM/BMP improves the density and height of the bone graft within three months after surgery. Patients who received DBM/BMP also experienced good results in terms of graft thickness and height. These findings suggest that DBM/BMP could be a promising option for enhancing bone healing in patients with cleft lip and palate. ^{2 3 4 5 6}

Who Is on the Research Team?

Matthew R Greives, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for patients with cleft lip and palate who have an open bone defect in the alveolus, cleared by an orthodontist for surgery. It excludes those with previous failed or successful alveolar bone grafts, without defects, non-consenting parents, or syndromic CLP.

Inclusion Criteria

Radiographically evident open bone defect of the alveolus

Dentition evaluated by orthodontist and cleared for ABG surgery

You have a cleft lip or palate, whether it affects one or both sides of your mouth.

Exclusion Criteria

Patients whose parents refuse to consent to randomization

Patients without an alveolar defect

Patients who have previously undergone successful ABG

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Alveolar Bone Grafting with either DBM/BMP or autologous ICBG

1 day

1 visit (in-person)

Post-operative Monitoring

Participants are monitored for post-operative complications such as fever, infection, and pain

1 week

1 visit (in-person)

Follow-up

Participants are monitored for graft success and other outcomes

3 months

2 visits (in-person)

Long-term Follow-up

Participants are assessed for health system costs and long-term graft success

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Control group (autologous ICBG)
• Intervention group (DBM/BMP)

Trial Overview The study compares two methods of alveolar bone grafting: one using Bone Morphogenic Protein/Demineralized Bone Matrix (DBM/BMP) and the other using autologous Iliac Crest Bone Graft (ICBG). It aims to assess cost-effectiveness, post-op pain, surgical time, and healing rates.

How Is the Trial Designed?

Group I: Intervention group (DBM/BMP) Experimental Treatment 1 Intervention

Patient undergoes Alveolar bone graft with DBM/BMP

Group II: Control group(autologous ICBG) Active Control 1 Intervention

Patient undergoes Alveolar Bone Graft with Iliac Crest Bone graft.

Control group (autologous ICBG) is already approved in European Union, United States for the following indications:

Approved in European Union as Autologous Iliac Crest Bone Graft for:

• Alveolar bone grafting for cleft lip and palate

Approved in United States as Autologous Iliac Crest Bone Graft for:

• Alveolar bone grafting for cleft lip and palate

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study of 98 patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF), the use of iliac crest bone grafting (ICBG) resulted in a significant increase in operative time and estimated blood loss compared to bone morphogenic protein (BMP)-2, but these increases were not clinically significant.

Despite the longer operative time, patients receiving ICBG did not experience higher levels of acute pain or increased narcotics consumption post-surgery, and ICBG was associated with lower total direct costs compared to BMP-2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iliac Crest Bone Graft for Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Prospective Analysis of Inpatient Pain, Narcotics Consumption, and Costs. Haws, BE., Khechen, B., Narain, AS., et al.[2022]

A systematic review of case-control studies found no significant differences in key outcomes like filling rate, volume, density, or failure rate between bone morphogenetic protein-2 (BMP-2) and iliac cancellous bone graft (ICBG) in alveolar cleft bone grafting (ACBG).

However, BMP-2 was associated with shorter operative times and reduced length of hospital stay compared to ICBG, suggesting it may offer practical advantages in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of bone morphogenetic protein-2 and iliac cancellous bone transplantation on alveolar cleft bone grafting: A meta-analysis. Xiao, WL., Jia, KN., Yu, G., et al.[2020]

Recombinant human bone morphogenetic protein (rhBMP)-2 combined with demineralized bone matrix is a viable alternative to iliac crest bone graft for alveolar cleft reconstruction, showing no increase in serious adverse events over a follow-up period of approximately 2.9 years.

While some local complications like facial swelling and minor wound dehiscence occurred in the rhBMP-2 group, most resolved without intervention, indicating a favorable safety profile compared to traditional grafting methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Analysis of Recombinant Human Bone Morphogenetic Protein-2 with a Demineralized Bone Matrix versus Iliac Crest Bone Graft for Secondary Alveolar Bone Grafts in Patients with Cleft Lip and Palate: Review of 501 Cases. Hammoudeh, JA., Fahradyan, A., Gould, DJ., et al.[2021]

Bone morphogenetic proteins (BMPs) significantly improve the fusion rate in lumbar fusion surgeries compared to iliac crest bone grafts, with a relative risk increase of 13%.

Using BMPs also leads to a lower reoperation rate and shorter operating time, while not increasing complications, blood loss, or hospital stay, indicating a safer and more efficient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta analysis of lumbar spinal fusion surgery using bone morphogenetic proteins and autologous iliac crest bone graft. Zhang, H., Wang, F., Ding, L., et al.[2022]

In a study of 170 patients undergoing spinal fusion with autologous iliac crest bone graft (ICBG), significant long-term complications were reported, including chronic pain and numbness at the harvest site, which affected daily activities and overall disability even 3.5 years post-surgery.

Persistent complications from ICBG were linked to worse patient-reported disability, suggesting that the long-term impact of these complications should be considered when evaluating the value of alternative bone graft substitutes like recombinant bone morphogenic protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of chronic pain associated with posterior autologous iliac crest bone graft harvest and its effect on postoperative outcome. Schwartz, CE., Martha, JF., Kowalski, P., et al.[2021]

In a study of 71 patients with alveolar cleft deformities, using DBX/rhBMP-2 for reconstruction resulted in significantly lower total operative costs ($4836) compared to traditional iliac crest bone grafting (ICBG) ($6892), despite higher material costs for DBX/rhBMP-2.

Patients receiving DBX/rhBMP-2 also experienced shorter operative times (67 minutes vs. 97.3 minutes) and reduced hospital stays (9.3 hours vs. 29.8 hours), making it a more efficient and cost-effective option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Demineralized Bone Matrix and rhBMP-2 versus Autologous Iliac Crest Bone Grafting in Alveolar Cleft Patients. Mehta, S., Blagg, R., Willcockson, J., et al.[2021]

In a study involving four patients with challenging soft tissue conditions, the use of bone morphogenetic protein (BMP)-2 combined with demineralized bone matrix (DBM) successfully reconstructed alveolar clefts without the need for traditional bone grafting, which often has a high failure rate.

This approach is recommended for patients with poor soft tissue quality, as it minimizes the risk of graft exposure and loss, suggesting that BMP-2 and DBM can be effective alternatives in high-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone Morphogenetic Protein-2 and Demineralized Bone Matrix in Difficult Bony Reconstructions in Cleft Patients. Makar, KG., Buchman, SR., Vercler, CJ.[2021]

In a study involving 20 patients with unilateral cleft lip and palate, both bovine-derived demineralized bone matrix (DMBM) and iliac crest grafts showed similar bone uptake at 6 months, with 70% for iliac crest and 69% for DMBM, indicating comparable short-term efficacy for secondary alveolar bone grafting.

While DMBM had no donor site morbidity and lower immediate surgical complications, it was associated with a higher cost and showed a trend towards lower net bone volume compared to iliac crest grafts over a longer follow-up period of 63 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Assessment of Autogenous Cancellous Bone Graft and Bovine-Derived Demineralized Bone Matrix for Secondary Alveolar Bone Grafting in Patients With Unilateral Cleft Lip and Palate. Kumar, V., Rattan, V., Rai, S., et al.[2022]

In a study of 131 patients with congenital unilateral alveolar clefts, the addition of BMP-2 to allograft bone (BIO-GENE) significantly improved the osteogenic rate compared to using autologous iliac crest bone graft alone.

There was no significant difference in osteogenesis rates between the allograft bone and autologous bone groups, indicating that both can be effective, but the combination of BMP-2 with allograft bone offers enhanced bone formation for cleft repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Application of Allograft Bone of Alveolar Cleft Repair. Chen, K., Zhang, Q., Chen, R., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10846763/

Early Results on the Efficacy of Demineralized Bone Matrix ... Early results evaluating the efficacy of alveolar bone grafting using DBX, rhBMP-2, and FDBC suggest feasibility in regard to graft height and thickness.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04234971

Cost Effectiveness in Alveolar Bone Grafting in Patients ... The purpose of this trial is to evaluate if the use of Bone Morphogenic Protein(BMP)/Demineralized Bone Matrix (DBM) versus the use of autologous Iliac Crest ...

3. mdpi.com mdpi.com/2075-1729/15/2/185

Efficacy of Recombinant Human Bone Morphogenetic ... Improved bone graft density and height were found three months following surgery in the rhBMP-2 group compared to the control group. Therefore, combining rhBMP- ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0266435620305647

Evaluating the efficacy of recombinant human bone ... This study aimed to evaluate the efficacy of rhBMP-2 in the treatment of alveolar cleft with autologous bone grafts by precise volumetric analysis.

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/10556656231159259?icid=int.sj-abstract.citing-articles.3

Efficacy of Demineralized Bone Matrix for Revision ... This study investigates the effectiveness of demineralized bone matrix (DBX) to close alveolar clefts in patients previously treated with bone morphogenic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6756658/

Safety and Efficacy of Recombinant Human Bone ... This study reviews the safety and efficacy of rhBMP-2 as applied to craniofacial reconstruction and assesses the level of scientific evidence currently ...