Extracoporeal Shock Wave Therapy (ESWT) for the Treatment of Detrusor Underactivity/ Underactive Bladder (DU/UAB)

Sponsor

Chang Gung Memorial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04161183

Collaborator

(none)

Enrollment

Location

Arms

33.5

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of ESWT for the treatment of patients with DU/UAB

Condition or Disease	Intervention/Treatment	Phase
Detrusor, Underactive Detrusor Underactivity	Device: Extracoporeal shock wave therapy Device: Placebo	N/A

Detailed Description

The prevalence of detrusor underactivity/ underactive bladder (DU/UAB) increased with age, which is 9-28% in young men (<50 years), and is up to 48% in the elderly men (>70 years) with non-neurogenic lower urinary tract symptoms. In women aged >70 years, the prevalence of DU ranged from 12% to 45%. Currently, there is a lack of effective pharmacological or surgical treatment of DU/UAB. Previously we demonstrated that extracoporeal shock wave therapy (ESWT) was able to mediate a partial recovery in the contractility of cryoinjury induced DU/UAB model in rats. Wang et al. reported the therapeutic effect of ESWT in the streptozotocin induced diabetic underactive bladder rat model with significantly improved voiding function, enhanced detrusor contractility, increased muscle actin expression and muscle proportion of the bladder wall, and recovery of neuronal integrity and innervations. Taken together, these findings suggest that a potential clinical benefit of ESWT treatment for patients with DU/UAB.

A total of 60 patients with DU/UAB will be enrolled to receive ESWT once a week for 6 weeks or placebo treatment. Patients with DU/UAB symptoms with post void residual (PVR) ≥ 100 mL and proven of DU/UAB without bladder outlet obstruction (BOO) by urodynamic study. Patients should not have uncontrolled acute urinary tract infection, and should not have treated with an investigational device, drug, or procedure for UAB within the last 3 months. Retreatment with ESWT at 3 months if patient reports ineffective will be allowed.

Primary end-point is the change of PVR volume (mL) from baseline to 1 month after treatment. Secondary endpoints include daily frequency, nocturia and FBC as record in 3-day voiding diary, Qmax, Pdet@Qmax, voided volume, PVR and global response assessment (GRA). One visit is required at baseline screening (before first treatment), treatment 1 (V1), treatment 2 (V2), treatment 3 (V3), treatment 4 (V4), treatment 5 (V5), treatment 6 (V6) and 1 month post V6 treatment (V7, primary end-point), and 3 months post V6 treatment (V8). Urine samples will be collected at each time-point for NGF and cytokines tests. Cystoscopy bladder biopsy will be performed at baseline and at 3 months post treatment, optional.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double blind, placebo control study. Eligible patients 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 (ESWT and Placebo) in 1: 1 ratio as shown below. The ESWT and placebo will be controlled by a research assistance who will not evaluate the therapeutic outcome to ensure the double-blind method.Double blind, placebo control study. Eligible patients 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 (ESWT and Placebo) in 1: 1 ratio as shown below. The ESWT and placebo will be controlled by a research assistance who will not evaluate the therapeutic outcome to ensure the double-blind method.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Extracoporeal Shock Wave Therapy (ESWT) for the Treatment of Detrusor Underactivity/ Underactive Bladder (DU/UAB) - a Single Center, Randomized, Double-blind, Placebo-controlled, Prospective Study

Actual Study Start Date :

Oct 15, 2019

Anticipated Primary Completion Date :

Jul 30, 2022

Anticipated Study Completion Date :

Jul 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo treatment (shock wave probe w/o energy)	Device: Placebo Probe be transcutaneous applied to the region of bladder dome, right upper lateral wall, right lower lateral wall, left upper lateral wall, and left lower lateral wall with 2500 shocks, frequency of 4 pulses per second but no energy once a week for 6 weeks
Experimental: Extracoporeal shock wave therapy Extracoporeal shock wave therapy (shock wave probe w/ energy)	Device: Extracoporeal shock wave therapy Probe be transcutaneous applied to the region of bladder dome, right upper lateral wall, right lower lateral wall, left upper lateral wall, and left lower lateral wall with 2500 shocks, frequency of 4 pulses per second and maximum total energy flow density 0.25 millijoule/mm2 once a week for 6 weeks

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo treatment (shock wave probe w/o energy)

Device: Placebo

Probe be transcutaneous applied to the region of bladder dome, right upper lateral wall, right lower lateral wall, left upper lateral wall, and left lower lateral wall with 2500 shocks, frequency of 4 pulses per second but no energy once a week for 6 weeks

Experimental: Extracoporeal shock wave therapy

Extracoporeal shock wave therapy (shock wave probe w/ energy)

Device: Extracoporeal shock wave therapy

Outcome Measures

Primary Outcome Measures

Net changes of the mean post void residual (PVR) volume (mL) from baseline to 1 month after the last treatment day [Baseline and 1 month]
Net changes of the PVR from baseline to 1 month after the last treatment day (higher PVR volumes represent a worse outcome)

Secondary Outcome Measures

Net changes of the functional bladder capacity (FBC) as assessed by the maximum urine volume (milliliters) as recorded in 3-day voiding diary [Baseline and 1 month]
Net changes of the functional bladder capacity (FBC) from baseline to 1 month after the last treatment day (higher FBC volumes represent a better outcome)
Net changes of the Global response assessment (GRA) [Baseline and 1 month]
Global response assessment (GRA) of therapeutic result by the patient (categorized from -3 to +3, indicating markedly worse to markedly improved) at 1 month after the last treatment day
Net changes of the maximum flow rate [Baseline and 1 month]
Net changes of the maximum flow rate from baseline to 1 month after the last treatment day (higher maximum flow rate represent a better outcome)
Net changes of the voided volume [Baseline and 1 month]
Net changes of the voided volume from baseline to 1 month after the last treatment day (higher voided volumes represent a better outcome)
Net changes of the Pdet@Qmax [Baseline and 1 month]
Net changes of the Pdet@Qmax from baseline to 1 month after the last treatment day
Net changes of the postvoid residual volume [Baseline and 1 month]
Net changes of the postvoid residual volume from baseline to 1 month after the last treatment day (lower postvoid residual volume represent a better outcome)
Changes of the Underactive Bladder Questionnaire (UAB-Q) score [Baseline and 1 month]
Changes of the UAB-Q score from baseline to 1 month after the last treatment day (lower UAB-Q score represent a better outcome)
Changes of urinary nerve growth factor and cytokines level [Baseline and 1 month]
Changes of the urinary nerve growth factor and cytokines level from baseline to 1 month after the last treatment day

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult male or female, at least 20 years of age.
History of UAB (defined as bothersome chronic incomplete bladder emptying) for at least 3 months documented in the medical record with recurring UAB symptoms.
No UAB symptom relief (unresponsiveness) with previous used medications and/or other treatments.
Voiding difficulty (complains of difficulty emptying the bladder).
UAB consistent with diabetes, MS, Parkinson's disease, or aging idiopathic.
Post void residual ≥ 100 mL.
Bladder capacity > 200 mL and < 800 mL.
Pressure flow Urodynamic testing demonstrating impaired detrusor contractility or areflexia without evidence of BOO, with maximum detrusor pressure Pdet at Qmax (Pdet@Qmax) of < 20 cmH2O and Maximum flow rate (Qmax) < 15 mL/sec for female, and BCI < 100 and BOOI < 40 for male.
Total UAB Questionnaire Score ≥ 3.
Females of child-bearing potential agree to use reliable birth control for the entire study duration.
Willing and capable of understanding and complying with all requirements of the protocol, including proper completion of the voiding diaries and self-administered questionnaires.
Free of active urinary tract infection.
Free of bladder outlet obstruction on enrollment.
Patient or his/her legally acceptable representative has signed the written informed consent form.
Subject on clean intermittent catheterization (CIC) should have been on CIC for at least 1 month and should be able to void spontaneously and not be completely dependent on CIC.

Exclusion Criteria:

Female patients who is pregnant, lactating, plans to become pregnant, or with child-bearing potential without contraception.
Simultaneously participating in another investigational drug or device study or use of any investigational drug(s) or therapeutic device(s) within 3 months preceding enrollment
Has been treated with an investigational device, drug, or procedure for UAB within the last 3 months.
History of cancer in pelvic organs, ureters, or kidneys or any cancer that has undergone treatment within the past 12 months.
Medical condition or disorder that may limit life expectancy or that may cause protocol deviations (e.g. unable to perform self-evaluations/accurately report medical history, and/or urinary symptoms).
History of spinal cord injury affecting urinary function.
Patients with uncontrolled acute urinary tract infection. An active urinary tract infection as evidenced by positive urine culture at the time of baseline assessment. If a UTI is confirmed in the baseline sample (e.g., positive urine culture containing

100,000 cfu/mL in midstream urine), the run-in period should be stopped. After successful treatment of the UTI, the patient can be rescreened and if eligible enroll in the study. If the patient has asymptomatic bacteriuria (i.e., a positive urine culture without clinical signs and symptoms of a UTI), the patient should not be excluded.

Currently taking medication(s) that may affect urination, including prescription drugs (i.e. anticholinergics, tricyclic antidepressants, bethanechol), over the counter drugs, dietary and/or herbal supplements, adrenergic antagonists. Alpha adrenergic blockers are allowed to use in a stable condition (longer than 1 month and keeping use during the study period).
Pelvic organ prolapses beyond the introitus (e.g., cystocele, rectocele).
Prior mesh surgery for stress urinary incontinence or pelvic prolapse.
Any other condition which per investigators' judgement, may affect the patient's safety (e.g. significant cardiovascular disease, asthma or other breathing disorders).
Patients with bladder outlet obstruction on enrollment.
Patients with any contraindication to be urethral catheterization during diagnostic test or treatment or follow-up period.
Patients have laboratory abnormalities at screening including:

ALT > 3 x upper limit of normal range AST > 3 x upper limit of normal range Serum creatinine level > 2 x upper limit of normal range.

Patients with any other serious disease considered by the investigator not in the condition to enter the trial.
Patients with cortisone treatment 6 week before first LESW therapy.

Other single item of Lab examination also can be retested per Investigator's discretion if abnormality. Patient will be rescreened and randomized into the study once confirmed eligible.