Amniotic Membrane Therapy for Interstitial Cystitis/Painful Bladder Syndrome

Amniotic Membrane Therapy for Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS): a Prospective, Double-Blind, Randomized Controlled 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Interstitial Cystitis; Painful Bladder Syndrome (PBS)
• Intervention / Treatment: Drug: Clarix Flo; Drug: Placebo

Detailed Description

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. These symptoms vary in severity and are known to cause significant impact on quality of life. Current recommended therapies include behavior modifications, stress management practices, physical therapy, oral pharmacologic pain management agents, intravesical instillations, hydrodistension, fulguration of bladder lesions and/or triamcinolone injections, intradetrusor onabotulinumtoxin A injections, neuromodulation, and major surgery.

Amniotic membranes, Clarix FLO™, have been used to assist in wound healing in many fields of medicine, and its use has evolved over the last century to various applications in regenerative medicine. A novel study using amniotic membranes for bladder therapy has showing promising preliminary results in a small cohort study of 10 females with recalcitrant IC/PBS. These women underwent intradetrusor injections of micronized amniotic membranes and had significant improvement of voiding symptoms and bladder pain over 3 months with no adverse events. No randomized controlled trials (RCT) of amniotic bladder therapy have been conducted to date. The proposed study would be the first RCT assessing the efficacy of amniotic membrane injections with Clarix FLO™ and has the potential to make significant impacts in the management and treatment of patients with IC/PBS.

Clarix FLO™ is a sterile, particulate human amniotic membrane and umbilical cord tissue product that is aseptically processed in compliance with current Good Tissue Practices from the same donated human tissue (placenta) after determination of eligibility and placenta/cord suitability. Amniotic Membrane and Umbilical Cord products are currently designated by the FDA as tissue products under PHS Act 361 HCT/P (human cells, tissues and cellular and tissue-based products). Clarix FLO™ does not contain living cells.

Patients will then be followed with clinical evaluation and questionnaires repeated at 2, 4, 8 and 12 weeks post-operatively. Additional urine culture and post void residuals will be repeated at 2 and 4 weeks post-operatively.

Primary Objective: Determine the efficacy of amniotic bladder therapy (ABT) in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) as defined by clinically-significant improvement

- Clinically-meaningful indicator defined as: 5 point reduction in Interstitial Cystitis Symptom Index (ICSI)

Secondary Objectives:

• Characterize duration of effect of ABT using clinical evaluation and the following questionnaires:

  • Interstitial Cystitis Symptom Index (ICSI)
  • Interstitial Cystitis Problem Index (ICPI)
  • Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS)
  • Overactive Bladder Assessment Tool
  • SF-12 Health Survey
• Determine if there are any adverse effects of ABT, such as urinary tract infections or acute urinary retention.

Hypothesis: ABT in patients with PBS improves clinical outcomes

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Margot Le Neveu, MD; Phone Number: 2013063828; Email: Margot.LeNeveu@uhhospitals.org
• Study Contact Backup: Name: David Sheyn, MD; Phone Number: 5132252314; Email: David.Sheyn@uhhospitals.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients 18 years of age or older
• Female
• English Speaking
• Diagnosis of IC/PBS
• Have failed at least one prior treatment for IC/PBS

Exclusion Criteria:

• Patients less than 18 years of age
• Unable to provide consent
• Non-English speaking
• Patients with known anatomical malformations of the ureters, bladder, or urethra

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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.	Drug: Placebo; 10 mL of 0.9% preservative-free sodium chloride
Experimental: Amniotic Membrane Therapy; Under general anesthesia, cystoscopy will be performed. A needle will be inserted into the detrusor muscle to a depth of approximately 2 mm. 100 mg 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.	Drug: Clarix Flo; 100 mg of commercially available micronized amniotic membrane (Clarix Flo; BioTissue, Miami, FL) diluted in 10 mL of 0.9% preservative-free sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Interstitial Cystitis Symptom Index (ICSI) score	Evaluate for clinically-meaningful reduction in symptoms as defined as a 5 point reduction in Interstitial Cystitis Symptom Index (ICSI)	To be completed pre-operatively and at 2, 4, 8 and 12 weeks post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Interstitial Cystitis Symptom Index Questionnaire	To determine the change in interstitial cystitis symptoms in participants who received amniotic membrane injection versus placebo injection (saline) as measured using the Interstitial Cystitis Symptom Index (ICSI).	To be completed pre-operatively and at 2, 4, 8 and 12 weeks post-operatively
Change in Interstitial Cystitis Problem Index Questionnaire	To determine the change in interstitial cystitis symptoms in participants who received amniotic membrane injection versus placebo injection (saline) as measured using the Interstitial Cystitis Problem Index (ICPI).	To be completed pre-operatively and at 2, 4, 8 and 12 weeks post-operatively
Change in Bladder Pain/ Interstitial Cystitis Symptom Score	To determine the change in interstitial cystitis symptoms in participants who received amniotic membrane injection versus placebo injection (saline) as measured using the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS).	To be completed pre-operatively and at 2, 4, 8 and 12 weeks post-operatively
Change in Overactive Bladder Assessment Tool Scores	To determine the change in interstitial cystitis symptoms in participants who received amniotic membrane injection versus placebo injection (saline) as measured using the Overactive Bladder Assessment Tool	To be completed pre-operatively and at 2, 4, 8 and 12 weeks post-operatively
Change in SF-12 Health Survey Scores	To determine the change in interstitial cystitis symptoms in participants who received amniotic membrane injection versus placebo injection (saline) as measured using the SF-12 Health Survey	To be completed pre-operatively and at 2, 4, 8 and 12 weeks post-operatively
Urinary tract infection	As defined by symptoms of urinary tract infection and positive urine culture	To be completed pre-operatively and at 2, 4, 8 and 12 weeks post-operatively

Collaborators and Investigators

• Sponsor: Case Western Reserve University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Cystitis; Pain; Cystitis, Interstitial
• Other Study ID Numbers: amnion_ic/pbs

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No