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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether fibroblast growth factor 2 (FGF2) heals chronic perforations (holes) in the eardrum more effectively than saline. Participants will receive either FGF2 or saline to determine which treatment closes the eardrum hole more effectively. The trial seeks individuals with a dry, central eardrum perforation present for over six months. This study builds on previous research to improve the success rate of eardrum healing. As a Phase 1 and Phase 2 trial, it aims to understand how FGF2 works in people and measure its effectiveness in a smaller group, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fibroblast growth factor 2 (FGF2) is safe for use on human eardrums. Studies have specifically examined its application on eardrums and found it well-tolerated. For instance, one study indicated that applying FGF2 to damaged eardrums did not cause any long-term negative effects, meaning participants did not experience harmful side effects over time. These findings support the safety of FGF2 for treating eardrum perforations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for a perforated eardrum, like watchful waiting or surgical repair, focus on allowing the body to heal naturally or mechanically patching the hole. But Fibroblast Growth Factor 2 (FGF2) works differently by stimulating tissue regeneration directly at the site of the perforation. Researchers are excited about FGF2 because it uses the body's own cellular processes to speed up healing, which could mean quicker recovery times and less need for surgical intervention. This innovative approach could offer a more efficient and less invasive solution for patients with this condition.

What evidence suggests that FGF2 might be an effective treatment for chronic tympanic membrane perforations?

This trial will compare the effectiveness of Fibroblast Growth Factor 2 (FGF2) with a saline control for treating perforated eardrums. Studies have shown that FGF2 effectively heals long-lasting eardrum holes. One study found that 92% of these holes completely closed after using FGF2. Another study reported success rates between 89.3% and 100% for closing these holes. Importantly, patients experienced better hearing and no serious side effects. These findings suggest that FGF2 is a promising option for treating chronic eardrum perforations. ^{2 4 6 7 8}

Who Is on the Research Team?

D. Bradley Welling, MD, PhD

Principal Investigator

Massachusetts Eye and Ear Infirmary

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7444771/

Topical fibroblast growth factor‐2 for treatment of chronic ... Hakuba et al in 2010 reported a 92% complete closure rate and near total closure in 5.7% of chronic tympanic membrane perforations with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02307916

Fibroblast Growth Factor Regeneration of Tympanic ... The goal is to determine the safety and efficacy of Fibroblast Growth Factor-2 (FGF-2) in the closure of chronic tympanic membrane perforations (TMP).

3. sciencedirect.com sciencedirect.com/science/article/pii/S0385814623001773

Outcomes of regenerative treatment for over 200 patients ... Our results showed that RT-TMP had high success rates for TMP closure and good hearing improvement and produced no severe complications that could affect ...

4. journals.lww.com journals.lww.com/otology-neurotology/fulltext/2020/07000/the_effectiveness_of_bfgf_in_the_treatment_of.20.aspx

The Effectiveness of bFGF in the Treatment of Tympanic... Objective: To investigate the effectiveness of basic fibroblast growth factor (bFGF) versus placebo or no intervention in the treatment of tympanic membrane (TM) ...

5. withpower.com withpower.com/trial/phase-2-tympanic-membrane-perforation-5-2024-5a7d0

FGF2 for Perforated Eardrum · Info for Participants 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6036947/

and long-term adverse effects of FGF-2 on tympanic ... This study suggests that the topical application of fibroblast growth factor-2 to human traumatic tympanic membranes is safe.

7. withpower.com withpower.com/trial/phase-3-tympanic-membrane-perforation-7-2021-6dfb4

FGF-2 for Ear Drum Perforation · Info for Participants The safety data for FGF-2 in treating tympanic membrane perforations includes findings from various studies. In a study on rats, a higher dose of FGF led to a ...

8. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/fgf_perfs

Do you have an ear drum perforation that has persisted for ... 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 ...