Growth Factors vs EMD for Periodontal Defects

Overseen By Arsalan Danesh, D.D.S

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nova Southeastern University

Must not be taking: Phenytoin, Alendronate

Disqualifiers: Pregnancy, Heavy smoking, Uncontrolled diabetes, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Treatment of intra-bony defects is challenging and requires extensive knowledge of the etiology, anatomy, occlusion, and available biomaterials that can be used to treat this kind of defects. Patients who received scaling and root planing at the college of dental medicine due to periodontal disease, will be screened for inclusion. Only subjects who showed persistent deep probing depth associated with an intrabony defect will be included and will be randomly allocated to one of two treatment groups. One group will be treated using recombinant human platelet derived growth factor (GEM-21) (test) added to allogenic bone graft, second group will be treated using enamel matrix derivatives (EMD) (control) with allograft. Both groups will be treated using the same surgical protocol. Patients will be followed up for a period of 6 months, before getting re-evaluated for assessing the effectiveness of the applied therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've been on medications affecting periodontal status in the past 6 months, like Phenytoin or Alendronate.

What data supports the effectiveness of this treatment for periodontal defects?

Research shows that recombinant human platelet-derived growth factor (rhPDGF-BB) is effective in promoting wound healing and bone regeneration in periodontal defects, with long-term stability observed in a 36-month study. Additionally, enamel matrix derivative (EMD) has been compared to other treatments and shown to be effective in treating periodontal defects. ^{1 2 3 4 5}

Is the treatment with growth factors and EMD safe for humans?

The safety of recombinant human growth hormone (rhGH), which is similar to growth factors, has been studied for over 30 years and is generally considered safe for approved uses. However, there are concerns about long-term risks like cancer, so ongoing monitoring is recommended. ^{6 7 8 9 10}

How is the drug GEM-21 (rhPDGF-BB) different from other treatments for periodontal defects?

GEM-21 (rhPDGF-BB) is unique because it uses a growth factor to stimulate the growth and repair of bone and periodontal tissues, promoting regeneration of the entire attachment apparatus, including bone, ligament, and cementum, which is not typically achieved with other treatments. ^{1 2 3 5 11}

Research Team

Theofilos Koutouzis, DDS, MS

Principal Investigator

Nova Southeastern University

Eligibility Criteria

This trial is for adults over 18 who've had scaling and root planing for periodontal disease, with deep pockets next to bone defects in their teeth. They must be able to come back for a 6-month check-up and not have serious health issues or habits like heavy smoking that could affect the results.

Inclusion Criteria

I am 18 years old or older.

I do not have any major health issues.

I have single or multiple rooted teeth in my upper or lower jaw.

Exclusion Criteria

I have a root tip infection in the area being tested.

Heavy smokers (>10 cigarettes a day)

I am willing to follow the study's rules and procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either rh-PDGF or EMD in combination with bone allograft for the treatment of intra-bony defects

6 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Enamel matrix derivatives (EMD)
• Recombinant human platelet derived growth factor (GEM-21)

Trial Overview The study compares two treatments on people with gum disease: one group gets human growth factor (Rh-PDGF) added to a bone graft, while the other gets enamel matrix derivatives (EMD) with a bone graft. Both groups follow the same surgery steps and are checked after six months.

Participant Groups

Group I: recombinant human platelet derived growth factor (rh-PDGF) in combination with bone allograft Experimental Treatment 1 Intervention

recombinant human platelet derived growth factor is a protein that is found in blood serum. It helps to recruit stem cells into the area to aid in cell differentiation and proliferation. When added to mineralized bone allograft, it stimulates the angiogenesis in the area, and this in turn may increase the outcomes of regeneration.

Group II: Enamel matrix derivatives (EMD) in combination with bone allograft. Active Control 1 Intervention

Enamel matrix derivatives are natural proteins that are produced in the developing dental follicle. It has been available for decades and has been proved to help in regeneration of intrabony defects when applied into the root surface. When combined with bone allograft, it results in regeneration of intrabony defects.

Recombinant human platelet derived growth factor (GEM-21) is already approved in United States, European Union for the following indications:

Approved in United States as GEM-21 for:

• Periodontal intra-bony defects

Approved in European Union as GEM-21 for:

• Periodontal intra-bony defects

Who Is Running the Clinical Trial?

Nova Southeastern University

Lead Sponsor

Trials

103

Recruited

12,000+

Findings from Research

Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) significantly improved linear defect fill (LDF) by 0.95 mm and clinical attachment level (CAL) gain by 0.34 mm compared to the control, indicating its efficacy in treating periodontal intra-bony defects.

Recombinant human fibroblast growth factor-2 (rhFGF-2) also showed significant improvement in LDF, with a 21.22% increase, suggesting it is effective as well, although rhPDGF-BB had a more pronounced effect overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of regenerative treatment with rhPDGF-BB and rhFGF-2 for periodontal intra-bony defects: a systematic review and meta-analysis. Khoshkam, V., Chan, HL., Lin, GH., et al.[2018]

The study involved 9 adult patients with advanced periodontitis and demonstrated that using purified recombinant human platelet-derived growth factor BB (rhPDGF-BB) mixed with bone allograft led to significant periodontal regeneration, including new bone, periodontal ligament, and cementum in both interproximal intrabony defects and Class II furcation lesions.

There were no safety concerns during the study, and the treatment resulted in substantial clinical improvements, with an average clinical attachment level gain of 6.17 mm and a vertical probing depth reduction of 6.42 mm in interproximal defects, indicating effective wound healing and regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. Nevins, M., Camelo, M., Nevins, ML., et al.[2022]

In a study involving 30 patients with chronic periodontitis, both platelet-rich fibrin (PRF) and enamel matrix derivative (EMD) were effective in treating periodontal intrabony defects, showing improvements in clinical parameters after 6 months.

However, EMD demonstrated a significantly greater percentage of defect resolution (43.07%) compared to PRF (32.41%), indicating that EMD may be the more effective option for this type of periodontal treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of platelet-rich fibrin vs. enamel matrix derivative in the treatment of periodontal intrabony defects: a clinical and cone beam computed tomography study. Gupta, SJ., Jhingran, R., Gupta, V., et al.[2022]

The growth-factor enhanced matrix (GEM) is a new clinical technology that combines recombinant human platelet-derived growth factor (rhPDGF-BB) with a bone scaffold, designed to enhance wound healing and bone regeneration.

Clinical and animal studies show that GEM effectively promotes wound healing, bone regeneration, and improves gingival attachment in difficult periodontal and peri-implant defects, highlighting its potential as a powerful treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new era in periodontal and periimplant regeneration: use of growth-factor enhanced matrices incorporating rhPDGF. Lynch, SE., Wisner-Lynch, L., Nevins, M., et al.[2018]

In a 36-month study involving 135 participants with localized severe periodontal defects, the use of recombinant human platelet-derived growth factor (rhPDGF-BB) significantly improved clinical outcomes, with 87% of patients in the 0.3 mg/mL group achieving a composite success benchmark compared to only 53.8% in the control group.

The study demonstrated that rhPDGF-BB treatment leads to long-term stability in clinical attachment levels and bone growth, indicating its effectiveness in promoting periodontal regeneration over an extended period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial. Nevins, M., Kao, RT., McGuire, MK., et al.[2022]

Recombinant DNA-derived human growth hormone (rhGH) has been effective in treating various growth disorders, achieving a final height increase of 5-7 cm in conditions like Turner syndrome and Prader-Willi syndrome, although this is less than the gains seen in growth hormone deficiency (GHD).

While rhGH has a good safety record, there are concerns about potential long-term risks of certain cancers, necessitating ongoing monitoring through national cancer registries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of growth hormone in children. Hindmarsh, PC., Dattani, MT.[2006]

In a 2-year study involving 148 adult patients with growth hormone deficiency, recombinant human growth hormone (rhGH) therapy significantly improved body composition, increasing lean body mass and total body water while reducing body fat and waist circumference, especially in the first year.

Despite the benefits, about one-third of patients experienced fluid-related side effects, suggesting that starting with lower doses of rhGH and adjusting them gradually may enhance safety and efficacy, as individual responses varied widely and could not be predicted by baseline characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two years of replacement therapy in adults with growth hormone deficiency. Verhelst, J., Abs, R., Vandeweghe, M., et al.[2019]

Recombinant human growth hormone (rhGH) has been deemed safe for approved uses in both children and adults, according to a consensus from the GH Research Society, but ongoing monitoring for long-term safety issues is essential.

Recent discussions among leading endocrine societies emphasize the need for continued surveillance regarding potential risks associated with rhGH, including cancer, glucose metabolism, and cardiovascular health, especially in adults who were treated as children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Allen, DB., Backeljauw, P., Bidlingmaier, M., et al.[2022]

In a study of 514 prepubertal children with idiopathic isolated growth hormone deficiency (GHD), baseline insulin-like growth factor-I (IGF-I) levels and stimulated peak growth hormone (GH) responses were found to be significant predictors of height velocity (HV) during the first year of rhGH treatment.

Children with moderate GHD showed an expected height velocity of 8.3 cm/year, indicating that identifying the severity of GHD through GH and IGF-I measurements can help tailor treatment strategies effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corroboration of Height Velocity Prediction Markers for rhGH With an Oral GH Secretagogue Treatment in Children With GHD. Blum, WF., Bright, GM., Do, MT., et al.[2022]

In a study involving 451 children with growth hormone deficiency, the weekly pegylated human growth hormone (Jintrolong) showed significantly greater increases in height velocity compared to daily rhGH after 25 weeks of treatment.

Both treatments had comparable safety profiles and compliance rates, indicating that Jintrolong is an effective and safe alternative to daily rhGH for managing growth hormone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies. Luo, X., Hou, L., Liang, L., et al.[2019]

In a study of 79 sites comparing the effects of enamel matrix derivative (EMD) and recombinant human fibroblast growth factor 2 (rhFGF-2) on early wound healing after periodontal surgery, rhFGF-2 showed significantly better outcomes in terms of redness and dehiscence scores.

The findings suggest that rhFGF-2 may enhance early wound healing more effectively than EMD, particularly in patients aged 50 and older and those with non-contained bone defects, although early healing did not predict radiographic bone fill after 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of early wound healing using modified papilla preservation technique between enamel matrix derivative and recombinant human fibroblast growth factor. Nakayama, Y., Tabe, S., Igarashi, K., et al.[2023]

References

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

Outcomes of regenerative treatment with rhPDGF-BB and rhFGF-2 for periodontal intra-bony defects: a systematic review and meta-analysis. [2018]

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

Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of platelet-rich fibrin vs. enamel matrix derivative in the treatment of periodontal intrabony defects: a clinical and cone beam computed tomography study. [2022]

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

A new era in periodontal and periimplant regeneration: use of growth-factor enhanced matrices incorporating rhPDGF. [2018]

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

Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Use of growth hormone in children. [2006]

7. England pubmed.ncbi.nlm.nih.gov

Two years of replacement therapy in adults with growth hormone deficiency. [2019]

8. England pubmed.ncbi.nlm.nih.gov

GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. [2022]

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

Corroboration of Height Velocity Prediction Markers for rhGH With an Oral GH Secretagogue Treatment in Children With GHD. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies. [2019]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Comparison of early wound healing using modified papilla preservation technique between enamel matrix derivative and recombinant human fibroblast growth factor. [2023]