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

Trial Summary

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 data supports the effectiveness of the treatment for Bone Grafting for Cleft Lip and Palate?

Research shows that using a combination of demineralized bone matrix and bone morphogenetic protein-2 (DBM/BMP) for bone grafting in cleft lip and palate patients can be as effective as the traditional method of using bone from the patient's own hip (iliac crest), with similar bone healing and fewer complications at the donor site. ^{1 2 3 4 5}

Is bone grafting for cleft lip and palate safe?

Bone grafting using iliac crest bone graft (ICBG) is generally safe but may cause chronic pain and numbness at the donor site. Using bone morphogenetic protein (BMP) with demineralized bone matrix (DBM) is also considered safe and avoids donor-site complications, though it may be more expensive. ^{1 3 6 7 8}

How does the treatment for bone grafting in cleft lip and palate differ from other treatments?

The treatment using bone morphogenetic protein (BMP)-2 with demineralized bone matrix (DBM) is unique because it avoids the need to harvest bone from the patient's own body, reducing donor-site complications and recovery time. This method is particularly beneficial for patients with poor soft tissue quality, where traditional bone grafting might fail. ^{1 2 3 4 9}

What is the purpose of this trial?

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 Bone Graft (ICBG) will result in an increase in total cost effectiveness for patients undergoing alveolar bone graft (ABG) for Cleft Lip and Palate (CLP) and to see if patients who are treated with DBM/BMP will have reduced post-operative pain scores,reduced operative times,and similar rates of bone healing compared to conventional ICBG.

Research Team

Matthew R Greives, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Outcomes of bone morphogenetic protein-2 and iliac cancellous bone transplantation on alveolar cleft bone grafting: A meta-analysis. [2020]

2. United States 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. [2021]

3. United States 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. [2021]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Application of Allograft Bone of Alveolar Cleft Repair. [2023]

6. United States 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A meta analysis of lumbar spinal fusion surgery using bone morphogenetic proteins and autologous iliac crest bone graft. [2022]

8. England 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. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Bone Morphogenetic Protein-2 and Demineralized Bone Matrix in Difficult Bony Reconstructions in Cleft Patients. [2021]