Assessing the Effectiveness and Safety of Interferon Bladder Infusion for the Treatment of Interstitial Cystitis

Study Overview
=================
Brief Summary
-----------------
Interstitial cystitis/bladder pain syndrome (IC/BPS) is one of the most intractable diseases of Urogynecology. The main clinical manifestations of interstitial cystitis/bladder pain are frequent urination and severe overflowing bladder pain. Due to the unclear pathological mechanism and the diversity of clinical manifestations and pathological features of the disease, the diagnosis is mainly to exclude suspicious diseases. At present, IC/BPS treatment mainly includes oral administration of mast cell stabilizing drugs such as sodium pentosan sulfate and anticholinergic drugs, or bladder instillation of dimethyl sulfone, hyaluronic acid and other drugs directly acting on the bladder mucosa, or surgical treatment such as sacrospinal radiculotomy and peripheral denervation of the bladder, but all can only relieve clinical symptoms and improve quality of life, and can not be targeted etiological treatment according to the pathological mechanism. Research showed JC polyomavirus (JCPyV) virus may be the original pathogen causing the development of IC/BPS. Interferon, as a broad-body antiviral agent, plays a critical role in triggering innate and adaptive immune responses against viral replication and infection. It can inhibit the replication and transcription of JCPyV through a variety of pathways. Interferon may be a potential specific drug for IC/BPS. Therefore, this study aims to evaluate the efficacy and safety of interferon bladder perfusion for IC/BPS.

Detailed Description
-----------------
The main manifestations of IC/BPS patients are pain, pressure or discomfort related to the bladder. Due to the unclear pathogenesis and inconsistent diagnostic criteria, accurate and effective clinical diagnosis and treatment of IC/BPS become very difficult. The diagnosis of IC/BPS is often uncertain and delayed, with patients moving from one hospital to another, often taking 2-11 years to get a final diagnosis. At present, the treatment of IC/BPS is mostly aimed at relieving clinical symptoms (including drugs, bladder perfusion, sacral nerve regulation, etc.), instead of radical treatment based on pathological mechanism. However, the long-term follow-up effect of commonly used clinical treatment is not good, with a recurrence rate of 70%. And about 10% of patients will eventually choose bladder resection because of the physical torture and mental stress caused by the disease. Previous studies confirmed that the positive rate of JCPyV in the urine of IC/BPS patients was 95%, while no JCPYV was found in the control group, suggesting that JCPYV may play an important role in the pathological mechanism of IC/BPS. The literature review also confirmed the presence of BK polyomaviruses (BKPyV) and JCPyV in IC/BPS urine, and a case of bladder perfusion therapy with interferon was reported to alleviate the frequency of urination and pain symptoms in IC/BPS patients, suggesting that interferon may be a potential specific drug for IC/BPS treatment. However, there are basically no relevant clinical studies at present. Therefore, this study aims to explore the efficacy and safety of interferon intravesical infusion therapy for IC/BPS. The research results are expected to improve the existing therapeutic means and explore new therapeutic targets. It lays an important foundation for the accurate treatment of IC/BPS.

Official Title
-----------------
Assessing the Effectiveness and Safety of Interferon Bladder Infusion for the Treatment of Interstitial Cystitis: a Randomized, Double-blind, Placebo-controlled Study

Conditions
-----------------
Interstitial Cystitis

Intervention / Treatment
-----------------
* Drug: Interferon
* Drug: Sodium Hyaluronate
* Drug: Sodium Chloride Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients over 18 years old, regardless of gender Combined with bladder pain/discomfort during urination, and at least one lower urinary tract symptom such as frequency and urgency, duration > 6 months The total score of O'Leary-Sant ICSI+ICPI is more than 18 points Agree to receive bladder perfusion therapy Exclusion Criteria: Have a history of allergy to interferon drugs Patients with serious heart, lung, liver, kidney or blood diseases, abnormal liver function, renal insufficiency, etc. Pregnant or lactating women A history of urinary tract infection within 12 weeks IC/ BPS-like symptoms caused by urinary diseases, such as overactive bladder, neurogenic bladder, urinary calculi, radiation cystitis, and endometriosis Within 24 weeks, patients had the following treatment history: bladder hydrodilation, intravesical laser treatment, pelvic floor reconstruction surgery Patients who have taken related drugs or participated in other clinical studies and received study drugs or medical device interventions within 3 months
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group drug<br>Generic name: Human interferon a2b injection; Dosage form: solution; Dosage: 1ml: 3 million IU; Frequency and duration: The first 4 weeks were irrigated once a week, a total of 4 times, and the last 4 months were irrigated once a month, a total of 4 times. The total treatment cycle was 5 months, and a total of 8 bladder perfusion treatments were performed. | Drug: Interferon<br>* The patient was seated in the seat and rested quietly. A three-way urinary tube was indwelled to drain urine. Interferon solution was configured according to the ratio of 3 million IU interferon +49ml normal saline. The urinary tube was clamped and the interferon solution was injected through the water inlet tube and retained for 30 minutes.<br>|
| Active Comparator: Sodium Hyaluronate<br>Generic name: Sterile sodium hyaluronate solution; Dosage form: solution; Dosage: 40mg/50ml; Frequency and duration: The first 4 weeks were irrigated once a week, a total of 4 times, and the last 4 months were irrigated once a month, a total of 4 times. The total treatment cycle was 5 months, and a total of 8 bladder perfusion treatments were performed. | Drug: Sodium Hyaluronate<br>* The patient was seated in the seat and rested quietly. A three-way urinary tube was indwelled to drain urine. The urinary tube was clamped and the sterile sodium hyaluronate solution was injected through the water inlet tube and retained for 30 minutes.<br>|
| Placebo Comparator: Sodium chloride injection<br>Generic name: Sodium chloride injection; Dosage form: solution; Dosage: 50ml: 0.45g; Frequency and duration: The first 4 weeks were irrigated once a week, a total of 4 times, and the last 4 months were irrigated once a month, a total of 4 times. The total treatment cycle was 5 months, and a total of 8 bladder perfusion treatments were performed. | Drug: Sodium Chloride Injection<br>* The patient was seated in the seat and rested quietly. A three-way urinary tube was indwelled to drain urine. The urinary tube was clamped and the sodium chloride injection was injected through the water inlet tube and retained for 30 minutes.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The score of global response assessment (GRA) pre- and post-treatment | The primary treatment outcomes were assessed using the Global Response Assessment (GRA) score (categorized into - 3, - 2, - 1, 0, 1, 2, and 3, indicating markedly worse to markedly improved status) | The time frame was from the date of bladder infusion to the date of final follow-up, ranging from 1 to 12 months | 
| The score of visual analogue scale (VAS) pre- and post-treatment | The score of VAS ranging from 0 to 10. Higher scores indicate higher levels of pain. | The time frame was from the date of bladder infusion to the date of final follow-up, ranging from 1 to 12 months | 
| Interstitial Cystitis Symptom Average Index (ICSI) questionnaires pre- and post-treatment | The O'Leary-Sant instrument is comprised of Symptom Index (score range: 0-20 points), which contains four questions related to urinary and pain symptoms. The score is calculated by summing the points for each item, and a score ≥6 points indicates IC. | The time frame was from the date of bladder infusion to the date of final follow-up, ranging from 1 to 12 months | 
| Interstitial Cystitis Problem Average Index (ICPI) questionnaires pre- and post-treatment | The O'Leary-Sant instrument is comprised of Problem Index (score range: 0-16 points), which contains four questions related to urinary and pain symptoms. The score is calculated by summing the points for each item, and a score ≥6 points indicates IC. | The time frame was from the date of bladder infusion to the date of final follow-up, ranging from 1 to 12 months | 
| The score of pelvic pain and urgency/frequency (PUF) pre- and post-treatment | The score ranges from 0 to 35 points. A score ≥5 points is considered to indicate IC. | The time frame was from the date of bladder infusion to the date of final follow-up, ranging from 1 to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related complications | Treatment-related complications, such as urinary tract infections, pain, psychiatric symptoms, changes in liver and kidney function, and gastrointestinal symptoms. | The time frame was from the date of bladder infusion to the date of final follow-up, ranging from 1 to 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Interstitial cystitis, Interferon, Bladder infusion