FGF2 for Perforated Eardrum

Overseen By D Bradley Welling, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: D. Bradley Welling, MD, PhD

Must not be taking: Corticosteroids, Immunosuppressants, Chemotherapy

Disqualifiers: Radiation treatment, Tympanoplasty failure, others

Compensation: Varies

Number of Visits: 6

Duration: 9 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare the application of fibroblast growth factor 2 (FGF2) with normal saline for the healing of chronic tympanic membrane (TM) perforations. This is an extension of a prior study. The main question it aims to answer is: Will modifications to our prior surgical trial provide higher success rates in obtaining complete closure of chronic tympanic membrane perforations? Twenty participants will be randomized in a controlled study to FGF2 or saline in a 3:1 ratio and the total tympanic membrane closure compared.

Will I have to stop taking my current medications?

The trial requires that you do not currently use corticosteroids, immunosuppressive agents, or chemotherapy. If you are taking any of these, you would need to stop before participating.

What data supports the effectiveness of the treatment Fibroblast Growth Factor 2 for perforated eardrum?

Research shows that Fibroblast Growth Factor 2 (FGF-2) can help heal eardrum perforations faster. In one study, rats treated with FGF-2 had their eardrum holes close in about 6.1 days, compared to 8.8 days for untreated ears. ^{1 2 3 4 5}

Is fibroblast growth factor-2 (FGF-2) safe for treating perforated eardrums?

FGF-2 appears to be generally safe for treating perforated eardrums, with some short-term side effects like ear discharge and rare cases of middle ear infection or re-perforation. No serious long-term side effects were found in studies. ^{1 2 4 6 7}

How does the treatment FGF2 differ from other treatments for perforated eardrum?

FGF2 (fibroblast growth factor 2) is unique because it is applied topically to the eardrum and works by promoting cell growth to speed up healing, which is different from surgical repair methods. It has been shown to significantly reduce healing time in animal studies compared to untreated cases. ^{1 2 3 8 9}

Research Team

D. Bradley Welling, MD, PhD

Principal Investigator

Massachusetts Eye and Ear Infirmary

Eligibility Criteria

This trial is for individuals with chronic tympanic membrane (eardrum) perforations. It's an extension of a previous study aiming to improve healing success rates.

Inclusion Criteria

Confirmed tympanic membrane perforation for 6 months or longer

Confirmed central perforation

I am 12 years old or older.

Exclusion Criteria

I currently have an ear infection.

I have had radiation treatment before.

I had ear surgery before, but it didn't work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to four applications of FGF2 or saline at 3-week intervals for tympanic membrane perforation repair

9 weeks

4 visits (in-person)

Follow-up

Participants are monitored for complete closure of tympanic membrane perforations and hearing outcomes

6 months

2 visits (in-person)

Treatment Details

Interventions

• Fibroblast Growth Factor 2

Trial Overview The trial compares the effectiveness of fibroblast growth factor 2 (FGF2) versus saline in healing eardrum perforations. Twenty participants will be randomly assigned to receive either FGF2 or saline at a ratio of 3:1.

Participant Groups

Group I: FGF2 active arm Experimental Treatment 1 Intervention

Active 0.1-0.2 ml of FGF2 will be placed on gelatin sponge in middle ear and on the lateral surface of the tympanic membrane and then covered with fibrin glue.

Group II: Saline control Placebo Group 1 Intervention

0.1-0.2 ml of normal sterile saline will be placed on gelatin sponge in middle ear and on the lateral surface of the tympanic membrane and then covered with fibrin glue.

Who Is Running the Clinical Trial?

D. Bradley Welling, MD, PhD

Lead Sponsor

Trials

1

Recruited

20+

Nobelpharma

Industry Sponsor

Trials

36

Recruited

2,200+

Findings from Research

In a phase 2 clinical trial involving 54 patients with chronic tympanic membrane perforations, fibroblast growth factor-2 (FGF-2) treatment did not show a statistically significant improvement in closure rates compared to a placebo, with closure rates of 57.5% for FGF-2 and 71.4% for placebo.

There were no significant differences in hearing outcomes between the FGF-2 and placebo groups, indicating that FGF-2 may not be an effective treatment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical fibroblast growth factor-2 for treatment of chronic tympanic membrane perforations. Santos, F., Shu, E., Lee, DJ., et al.[2022]

Topical application of 400 ng of fibroblast growth factor (FGF) significantly accelerated the healing of tympanic membrane perforations in rats, reducing the closure time from 8.8 days in untreated ears to 6.1 days.

Higher doses of FGF led to complications such as myringitis, while a dose of 200 ng did not show any significant difference compared to the placebo, indicating that the optimal dose for healing is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblast growth factor improves the healing of experimental tympanic membrane perforations. Mondain, M., Saffiedine, S., Uziel, A.[2019]

In a study of 138 patients with traumatic tympanic membrane perforations, the use of fibroblast growth factor-2 (FGF-2) delivered via Gelfoam patches resulted in a significantly higher closure rate of 97.9% compared to 70.7% in the observation group.

FGF-2 plus Gelfoam patches not only improved closure rates but also reduced closure times to an average of 15.7 days, making it a promising minimally invasive treatment option for tympanic membrane perforations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fibroblast growth factor-2 delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic eardrum perforations lying close to the malleus. Jin, ZH., Dong, YH., Lou, ZH.[2018]

Fibroblast growth factor-2 has shown a high success rate (89.3-100%) in regenerating tympanic membrane perforations in humans, with an average closure time of about 2 weeks, indicating its efficacy in treating both acute and chronic cases.

When combined with Gelfoam, fibroblast growth factor-2 achieved an impressive success rate of 83-98.1% for chronic perforations, compared to only 10% for those treated with gelatine sponge alone, highlighting its potential advantages over traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regeneration of the tympanic membrane using fibroblast growth factor-2. Lou, ZC., Lou, ZH., Xiao, J.[2018]

In a mouse model of chronic tympanic membrane perforations, heparin binding epidermal growth factor-like growth factor (HB-EGF) demonstrated a significantly higher healing rate (83.3%) compared to fibroblast growth factor 2 (FGF2, 31.6%) and epidermal growth factor (EGF, 15.8%).

The study suggests that HB-EGF not only promotes better healing but also results in tympanic membranes that resemble normal structure, indicating its potential as an effective nonsurgical treatment option for chronic TM perforations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model. Santa Maria, PL., Weierich, K., Kim, S., et al.[2018]

References

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

Topical fibroblast growth factor-2 for treatment of chronic tympanic membrane perforations. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Fibroblast growth factor improves the healing of experimental tympanic membrane perforations. [2019]

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

The effects of fibroblast growth factor-2 delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic eardrum perforations lying close to the malleus. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Regeneration of the tympanic membrane using fibroblast growth factor-2. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Effects of basic fibroblast growth factor dose on traumatic tympanic membrane perforation. [2014]

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

Repair of chronic tympanic membrane perforations with fibroblast growth factor. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

The short- and long-term adverse effects of FGF-2 on tympanic membrane perforations. [2019]

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

Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Risk factors affecting human traumatic tympanic membrane perforation regeneration therapy using fibroblast growth factor-2. [2016]