Transvaginal Botulinum Toxin A for Interstitial Cystitis / Bladder Pain Syndrome

Study Overview
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Brief Summary
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Interstitial cystitis / bladder pain syndrome (IC/BPS) is a debilitating condition that affects millions of women in the United States. Women suffer from recurring pelvic pain, bladder pressure, painful bladder, urinary frequency (needing to go often) and urgency (feeling a strong need to go). Women are five times more likely to suffer from IC/BPS than men. IC/BPS is a common cause of painful bladder after excluding urinary tract infection. About one-third of women resort to opioids, thus contributing to the current opioid crisis. Sadly, there are no durable treatments and the majority of therapies are not FDA-approved for IC/BPS.

Detailed Description
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Botulinum toxin A (BTA) injected into the bladder wall off-label for the IC/BPS indication has been effective in many women. Unfortunately most women cannot get BTA injection without general anesthesia due to pain from cystoscopy (small camera placed in the bladder). Dr. Dobberfuhl and her team created the transvaginal trigone treatment (T3) approach. Dr. Dobberfuhl was the first investigator in the world to complete a clinical trial of 31 injections of T3 BTA through the vaginal approach, for a non-painful condition, overactive bladder. The T3STOPBPS study is an open label dose-escalation clinical study of BTA, for women with refractory IC/BPS. BTA is injected through the vaginal wall using a simple technique, the T3 approach, without the need for anesthesia or cystoscopy. The T3 BTA injection procedure has been well tolerated. The T3STOPBPS study will generate data needed for NIH R01 funding which will 1. Bring us closer to making T3 BTA available to women with IC/BPS, 2. Identify neuropeptide (pain) signaling targets for new IC/BPS therapies, and 3. Improve our understanding of fNIRS brain connectivity associated with IC/BPS treatment success. Twelve patients will be recruited from the clinical practice of Dr. Dobberfuhl to undergo 50 unit T3 BTA injection at baseline. Psychometrically validated questionnaires (AUASS, ICIQ FLUTS, SF12, OLS ICSI / ICPI), voiding diaries, fNIRS and whole urine will be obtained at baseline (pre-treatment), 6 and 12 weeks after T3 BTA. Noninvasive fNIRS brain testing will be performed in collaboration with Dr. Hosseini, which will assess changes in cerebral connectivity from baseline. Whole urine will assess changes in neuropeptide molecular signaling using bulk RNA sequencing following T3 BTA treatment. RNA sequencing will be correlated with our single cell sequencing bladder biopsy data in IC/BPS. Following 50 unit T3 BTA injection, after the 12 week study visit, subjects will be offered dose escalation to 100 units if they do not achieve >50% improvement in PGIC. Milestone for T3 BTA efficacy will be met if >50% improvement is achieved in PGIC versus baseline. Subjects will be eligible for repeat BTA injection when they report less than 50% improvement in symptoms according to the patient global impression of change (PGIC) scale after the 12 week study visit. This will help us understand how long the effect of the BTA lasts, which is typically 3 to 12 months with the traditional cystoscopic route of delivery. A new consent form will be signed at the time of repeat injection.

Official Title
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T3STOPBPS: Open Label Clinical Trial of Transvaginal Trigone Treatment (T3) With Botulinum Toxin A (BTA) for Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS)

Conditions
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Interstitial Cystitis, Bladder Pain Syndrome

Intervention / Treatment
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* Drug: Transvaginal botulinum toxin A (BTA) injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females with IC/BPS Females who are considering intradetrusor BTA chemodenervation for the treatment of refractory IC/BPS Exclusion Criteria: Involvement in other studies with potentially overlapping indications or symptoms Patients who are unable to undergo a transvaginal intervention as a result of anatomic barriers or discomfort will be excluded from enrollment patients known to be pregnant or breastfeeding Known allergy to BTA injection therapy or lidocaine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transvaginal Botulinum Toxin A (BTA) injection<br>Botulinum toxin A (Botox® 100 units) will be injected into the detrusor muscle of the bladder by inserting a needle through the anterior vaginal wall. | Drug: Transvaginal botulinum toxin A (BTA) injection<br>* Botulinum toxin A (Botox® 100 units) will be injected into the detrusor muscle of the bladder by inserting a needle through the anterior vaginal wall.<br>* Other names: Botox® 100 units;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Patient Global Impression of Change (PGIC) scale | Patients will be classified as treatment success if they achieve our primary efficacy outcome of a >50% improvement in the Patient Global Impression of Change (PGIC) scale | Baseline through week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in American Urological Association Symptom Score (AUASS) | American Urological Association Symptom Score | Baseline through week 12 | 
| Change from baseline in International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms (ICIQ FLUTS) | International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms | Baseline through week 12 | 
| Change from baseline in Short Form 12-item Survey (SF12) | Short Form 12-item Survey | Baseline through week 12 | 
| Change from baseline in O'Leary Sant (OLS) Symptom Score [Interstitial Cystitis Symptom Index (ICSI) / Interstitial Cystitis Problem Index (ICPI)] | O'Leary Sant Symptom Score (Interstitial Cystitis Symptom Index / Interstitial Cystitis Problem Index) | Baseline through week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IC/BPS