Amniotic Membrane Therapy for Interstitial Cystitis

Overseen By David Sheyn, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: David Sheyn

Disqualifiers: Anatomical malformations, others

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

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

Compensation: Varies

Number of Visits: 5

Duration: Immediate (single procedure)

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a clinical syndrome in which patients report symptoms of bladder and/or pelvic pain with pressure and/ or discomfort associated with urinary frequency and urgency. The primary objective of this study is to determine the efficacy of amniotic membrane therapy in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) as defined by clinically-significant improvement in validated symptom questionnaires.

Do I need to stop my current medications for the trial?

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

What data supports the effectiveness of the treatment Amniotic Membrane Therapy for Interstitial Cystitis?

Amniotic membranes are known for their wound healing abilities in various medical fields, and early reports suggest they may help heal the bladder lining in interstitial cystitis, potentially reducing symptoms like pain and frequent urination. ^{1 2 3 4 5}

Is Amniotic Membrane Therapy safe for humans?

Amniotic Membrane Therapy has been used safely in various medical treatments, such as eye conditions and bone repair, with no major safety concerns reported. It is prepared under sterile conditions and tested for viruses to ensure safety. ^{6 7 8 9 10}

How is Amniotic Membrane Therapy different from other treatments for interstitial cystitis?

Amniotic Membrane Therapy is unique because it uses components from the amniotic membrane, which have anti-inflammatory and healing properties, and is applied directly to the affected area, unlike traditional treatments that may involve oral medications or bladder instillations. ^{6 11 12 13 14}

Research Team

David Sheyn

Principal Investigator

University Hospitals Cleveland Medical Center

Eligibility Criteria

This trial is for English-speaking women aged 18 or older who have been diagnosed with Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) and haven't found relief from at least one previous treatment.

Inclusion Criteria

I have tried at least one treatment for bladder pain syndrome that didn't work.

I am female.

I am 18 years old or older.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amniotic membrane therapy or placebo injections under general anesthesia

Immediate (single procedure)

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness with clinical evaluations and questionnaires at 2, 4, 8, and 12 weeks post-operatively

12 weeks

4 visits (in-person)

Treatment Details

Interventions

• Amniotic Membrane Therapy

Trial Overview The study aims to test the effectiveness of amniotic membrane therapy (Clarix Flo) compared to a placebo in improving symptoms of IC/PBS, as measured by responses to symptom questionnaires.

Participant Groups

Group I: Amniotic Membrane Therapy Experimental Treatment 1 Intervention

Under general anesthesia, cystoscopy will be performed. A needle will be inserted into the detrusor muscle to a depth of approximately 2 mm. 100mg of commercially available micronized amniotic membrane (Clarix Flo; BioTissue, Miami, FL) diluted in 10 mL of 0.9% preservative-free sodium chloride, and 0.5 mL of the solution will be injected into 20 equally spaced sites into the posterior and lateral walls of the bladder, sparing the dome and the trigone.

Group II: Placebo Placebo Group 1 Intervention

Under general anesthesia, cystoscopy will be performed. A needle will be inserted into the detrusor muscle to a depth of approximately 2 mm. 0.5 mL of 10 mL of 0.9% preservative-free sodium chloride will be injected into 20 equally spaced sites into the posterior and lateral walls of the bladder, sparing the dome and the trigone.

Amniotic Membrane Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Amniotic Membrane Therapy for:

• Lower-extremity diabetic skin ulcers
• Certain ophthalmic indications

Approved in European Union as Amniotic Membrane Therapy for:

• Lower-extremity diabetic skin ulcers
• Certain ophthalmic indications

Who Is Running the Clinical Trial?

David Sheyn

Lead Sponsor

Trials

5

Recruited

390+

Findings from Research

In a study of 12 women with interstitial cystitis who received one course of intravesical dimethyl sulphoxide (DMSO) therapy, most maintained symptom relief during pregnancy, suggesting that DMSO treatment may be safe and effective for managing symptoms in pregnant patients.

All 13 pregnancies resulted in healthy babies, indicating that pregnancy outcomes are favorable after DMSO treatment for interstitial cystitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy outcomes following the diagnosis of interstitial cystitis. Onwude, JL., Selo-Ojeme, DO.[2017]

Mesenchymal stem cells (MSC) show promise as a new treatment for Interstitial Cystitis (IC) due to their unique abilities to produce a conditioned medium (CM) rich in growth factors and cytokines that can enhance bladder regeneration.

MSC-CM possesses multiple beneficial properties, including anti-inflammatory and immunomodulatory effects, making it a potential candidate for intravesical therapy to alleviate symptoms and prevent recurrence of IC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials. Adamowicz, J., Pokrywczyńska, M., Drewa, T.[2022]

In a study involving 10 female patients with chronic interstitial cystitis/bladder pain syndrome (IC/BPS), intra-detrusor injections of micronized amniotic membrane (AM) significantly improved bladder pain and voiding symptoms over a 3-month period, with no adverse events reported.

The treatment led to a substantial decrease in the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) from 37.4 to 12.2, indicating a marked improvement in both physical and mental quality of life for the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early three-month report of amniotic bladder therapy in patients with interstitial cystitis/bladder pain syndrome. Madan, R., Radoiu, C., Liaw, A., et al.[2023]

Alternative therapies are increasingly sought by patients with interstitial cystitis who do not find relief from conventional allopathic treatments, indicating a need for more diverse treatment options.

The review highlights various alternative and additive methods that have been reported as effective supportive treatments for interstitial cystitis, suggesting their potential role in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Alternative and complementary therapeutic measures in interstitial cystitis]. Herwig, R., Oberpenning, F.[2019]

Pentosan polysulfate sodium (Elmiron) is currently the only FDA-approved oral treatment for painful bladder syndrome/interstitial cystitis, providing symptom relief after several months of use.

The article suggests that human chorionic gonadotropin may have therapeutic potential for treating this chronic bladder disease, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Human Chorionic Gonadotropin Against Painful Bladder Syndrome/Interstitial Cystitis. Rao, CV.[2017]

In a study of 12 patients with severe bacterial keratitis, combining early amniotic membrane transplantation (AMT) with topical corticosteroids resulted in significant pain relief, reducing pain scores from a median of 8 to 2 within three days after treatment.

The treatment also facilitated corneal epithelial healing, with recovery times averaging 25.5 days, and no serious complications like perforation or neovascularization were observed, indicating a safe approach to managing severe bacterial keratitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation in severe bacterial keratitis. Gicquel, JJ., Bejjani, RA., Ellies, P., et al.[2013]

Amniotic membrane transplantation (AMT) was successful in treating postinfectious corneal ulceration in 62.8% of the 43 patients studied, indicating its efficacy as a therapeutic option for severe cases.

The median healing time after AMT was 40 days, but patients experienced a decrease in best-corrected visual acuity (BCVA) compared to baseline, highlighting the need for careful patient selection and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic Membrane Transplantation in the Management of Corneal Ulceration Following Infectious Keratitis. Lamas-Francis, D., Navarro, D., Moreno, C., et al.[2023]

Amniotic membrane implantation as a therapeutic contact lens is a safe and effective treatment for epithelial defects, with no intra- or postoperative complications reported in a study of 20 patients.

Longer retention of the amniotic membrane (over 1 week) significantly increases the chances of complete epithelialization, especially in patients with persistent defects, highlighting the importance of maintaining the implant in place for optimal healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane implantation as a therapeutic contact lens for the treatment of epithelial disorders. Gris, O., del Campo, Z., Wolley-Dod, C., et al.[2019]

In an animal study involving 4 dogs, the use of amniotic membrane over a xenograft significantly increased bone formation in dental defects, with an average bone quantity of 56.81 mm compared to 37.38 mm in the control group, showing a statistically significant difference (P = 0.025).

The amniotic membrane also reduced inflammation intensity post-surgery, with moderate inflammation (50%) in the test group versus severe inflammation (62.5%) in the control group, indicating its potential to enhance healing and reduce discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane as an accelator in mandibular bone defects repair. Samandari, MH., Tamizifar, A., Hosseinian, M., et al.[2023]

The human amniotic membrane (AM) is effective in treating severe ocular surface diseases due to its properties that promote epithelial cell growth and reduce abnormal blood vessel formation.

AM transplantation (AMT) is a safe procedure, but patients should be informed that it may temporarily decrease visual acuity as the membrane is not completely transparent and will be absorbed within 4-6 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation and preservation of amniotic membrane. Dekaris, I., Gabrić, N.[2019]

In a case series of 28 patients with severe corneal surface disorders treated with amniotic membrane transplantation, 25% experienced serious complications, including spontaneous corneal perforation and descemetocele within 6 weeks.

These complications may be linked to the severity of the underlying conditions or the effects of the amniotic membrane on corneal fibroblasts, highlighting the need for careful consideration of risks when opting for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation in severe ocular surface disorders. Kaup, M., Redbrake, C., Plange, N., et al.[2022]

In a study involving 47 rats with bacterial keratitis, the combination of cefazolin drops and amniotic membrane (AM) transplantation resulted in the best clinical outcomes, showing less corneal haze and neovascularization compared to other treatments.

The use of AM transplantation significantly improved the healing process, as indicated by lower bacterial counts and less congested blood vessels in the corneas of treated rats, suggesting its effectiveness as an adjunctive treatment in corneal healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of amniotic membrane transplantation on the healing of bacterial keratitis. Barequet, IS., Habot-Wilner, Z., Keller, N., et al.[2013]

Amniotic membrane transplantation (AMT) is effective in promoting healing and preventing corneal perforation in patients with acute fungal keratitis, with a 75% epithelialization rate in patients with active infections.

Despite its effectiveness, there is a risk of persistent or recurrent fungal infections, highlighting the need for ongoing antifungal treatment and careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation for persistent corneal ulcers and perforations in acute fungal keratitis. Chen, HC., Tan, HY., Hsiao, CH., et al.[2022]

Amniotic membrane transplantation (AMT) in seven patients with acute herpetic keratitis led to significant healing of corneal ulcers and reduction of inflammation, with epithelial defects healing in an average of 17 days.

No serious side effects were reported, and vision improved in most patients, suggesting that AMT is a promising treatment option for restoring ocular surface integrity in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of acute ulcerative and necrotising herpes simplex and zoster keratitis with amniotic membrane transplantation. Heiligenhaus, A., Li, H., Hernandez Galindo, EE., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Pregnancy outcomes following the diagnosis of interstitial cystitis. [2017]

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

Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Early three-month report of amniotic bladder therapy in patients with interstitial cystitis/bladder pain syndrome. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[Alternative and complementary therapeutic measures in interstitial cystitis]. [2019]

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

Therapeutic Potential of Human Chorionic Gonadotropin Against Painful Bladder Syndrome/Interstitial Cystitis. [2017]

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

Amniotic membrane transplantation in severe bacterial keratitis. [2013]

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

Amniotic Membrane Transplantation in the Management of Corneal Ulceration Following Infectious Keratitis. [2023]

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

Amniotic membrane implantation as a therapeutic contact lens for the treatment of epithelial disorders. [2019]

9. Iran pubmed.ncbi.nlm.nih.gov

Amniotic membrane as an accelator in mandibular bone defects repair. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Preparation and preservation of amniotic membrane. [2019]

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

Amniotic membrane transplantation in severe ocular surface disorders. [2022]

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

Effect of amniotic membrane transplantation on the healing of bacterial keratitis. [2013]

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

Amniotic membrane transplantation for persistent corneal ulcers and perforations in acute fungal keratitis. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Management of acute ulcerative and necrotising herpes simplex and zoster keratitis with amniotic membrane transplantation. [2022]