Low Energy Shock Wave for the Treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)

Study Overview
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Brief Summary
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To investigate the efficacy and safety of LESW on participants with IC/BPS

Detailed Description
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Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW has been proved to have therapeutic effects in patients with nonbacterial prostatitis and chronic pelvic pain syndrome (CPPS). Investigator's previous study has demonstrated that LESW treatment inhibited nerve growth factor (NGF), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) expression, and blocked the bladder pain, inflammation and overactivity in a cyclophosphamide induced cystitis model in rats. These findings suggest that a potential clinical benefit of LESW treatment for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). A total of 50 participants with IC/BPS will be enrolled to receive LESW (transcutaneous applied to the suprapubic bladder region with 2000 shocks, frequency of 3 pulses per second and maximum total energy flow density 0.25 millijoule/mm2) once a week for 4 weeks or placebo (same condition but with no energy) treatment. All participants should have IC symptoms for at least 6 months, and have received cystoscopy to rule out other bladder lesion. Participants should not have urinary tract infection (UTI) in recent 3 months, and no urinary tract stone. Participants should not receive intravesical hyaluronic acid treatment in recent 3 months, or intravesical Botox injection in recent 12 months. Retreatment with LESW at 3 months if participants reports ineffective. Primary end-point is the change of the O'Leary-Sant symptom score (OSS), including Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) from baseline to 1 month after treatment. Secondary endpoints include Visual Analogue Scale (VAS), daily frequency, nocturia and functional bladder capacity (FBC) as record in 3-day voiding diary, maximum flow rate (Qmax), voided volume, postvoiding residual (PVR) and global response assessment (GRA). Two visits are required at baseline screening (before first treatment), treatment (V1), 1 week (V2), 2 weeks (V3), 3 weeks (V4) and 1 week post V4 treatment (V5), 1 month post V4 treatment (V6, primary end-point), and 3 months post V4 treatment (V7) . Urine samples will be collected at each time-point for NGF and cytokines tests. Bladder biopsy will be performed at baseline and repeat cystoscopy at 3 months post treatment optional.

Official Title
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Low Energy Shock Wave for the Treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) - a Randomized, Double-blind, Placebo-controlled, Prospective Study

Conditions
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Interstitial Cystitis

Intervention / Treatment
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* Device: Low energy shock wave
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with age of 20 years old or above Patients with symptoms of unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six months duration, in the absence of infection or other identifiable causes Patients has received cystoscopy and ruled out other bladder lesion Free of active urinary tract infection Free of bladder outlet obstruction on enrollment Free of overt neurogenic bladder dysfunction and limitation of ambulation Patient or his/her legally acceptable representative has signed the written informed consent form Exclusion Criteria: Patients had received intravesical hyaluronic acid treatment in recent 3 months, or intravesical Botox injection in recent 12 months Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up Patients with bladder outlet obstruction on enrollment Patients with PVR >100 ml Patients with uncontrolled confirmed diagnosis of acute urinary tract infection Patients have laboratory abnormalities at screening including: alanine aminotransferase (ALT)> 3 x upper limit of normal range, and aspartate aminotransferase (AST) > 3 x upper limit of normal range Patients have abnormal serum creatinine level > 2 x upper limit of normal range Female patients who is pregnant, lactating, or with child-bearing potential without contraception Patients with any other serious disease considered by the investigator not in the condition to enter the trial Patients had received intravesical treatment for IC within recent 1 month Patients had participated investigational drug trial within 1 month before entering this study Patients with coagulopathy

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind, placebo control study. Eligible participants will be assigned a randomization number in sequential order and each of the randomization will determine the allocation of one of the two treatment groups (LESW and Placebo) in 1: 1 ratio as shown below. The LESW and placebo will be controlled by a research assistance who will not evaluate the therapeutic outcome to ensure the double blind method.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo treatment (shock wave probe w/o energy) | Device: Placebo<br>* Probe be transcutaneous applied to the suprapubic bladder region with 2000 shocks, frequency of 3 pulses per second but no energy once a week for 4 weeks<br>|
| Experimental: Low energy shock wave<br>Low energy shock wave treatment (shock wave probe w/ energy) | Device: Low energy shock wave<br>* Probe be transcutaneous applied to the suprapubic bladder region with 2000 shocks, frequency of 3 pulses per second and maximum total energy flow density 0.25 millijoule/mm2 once a week for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the O'Leary-Sant symptom score (OSS, including ICSI and ICPI) | Change of the O'Leary-Sant symptom score from baseline to 1 month after the treatment day. Subscales ICSI and ICPI are graded from 0 to 20 and 0 to 16, respectively. The items are summed to obtain OSS (range from 0 to 36, higher values represent a worse outcome). | Baseline and 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net changes of the Visual Analog Scale (VAS) | Net changes of the Visual Analog Scale from baseline to 1 month after the treatment day (VAS range from 0 to 10, higher values represent a worse outcome) | Baseline and 1 month | 
| Net changes of the functional bladder capacity (FBC) as assessed by the maximum urine volume (milliliters) as recorded in 3-day voiding diary | Net changes of the functional bladder capacity (FBC) from baseline to 1 month after the treatment day (higher FBC volumes represent a better outcome) | Baseline and 1 month | 
| Net changes of the voiding frequency at daytime as recorded in 3-day voiding diary | Net changes of the voiding frequency at daytime as recorded in 3-day voiding diary from baseline to 1 month after the treatment day (higher voiding frequency at daytime represent a worse outcome) | Baseline and 1 month | 
| Net changes of the voiding frequency at night time as recorded in 3-day voiding diary | Net changes of the voiding frequency at night time as recorded in 3-day voiding diary from baseline to 1 month after the treatment day (higher voiding frequency at night time represent a worse outcome) | Baseline and 1 month | 
| Net changes of the Global response assessment (GRA) | Global response assessment (GRA) of therapeutic result by the patient (categorized from -3 to +3, indicating markedly worse to markedly improved) at 3 months after the last treatment day | Baseline and 3 month | 
| Net changes of the maximum flow rate | Net changes of the maximum flow rate from baseline to 1 month after the treatment day (higher maximum flow rate represent a better outcome) | Baseline and 1 month | 
| Net changes of the voided volume | Net changes of the voided volume from baseline to 1 month after the treatment day (higher voided volumes represent a better outcome) | Baseline and 1 month | 
| Net changes of the PVR | Net changes of the PVR from baseline to 1 month after the treatment day (higher PVR volumes represent a worse outcome) | Baseline and 1 month | 
| Net changes of the cytokines level | Net changes of the cytokines level from baseline to 1 month after the treatment day (e.g. NGF and IL-6, higher values represent a worse outcome) | Baseline and 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low Energy Shock Wave (LESW), Extracorporeal Shockwave Therapy, interstitial cystitis/bladder pain syndrome (IC/BPS)