Clinical trial NCT04565925: Sildenafil for Treatment of Urinary Incontinence in Patients With Spinal Cord Injuries
Official title: Sildenafil for Treatment of Urinary Incontinence in Patients With Spinal Cord Injuries
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Spinal Cord Injuries
Urinary Incontinence
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2020-09-25
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each subject will be administered both sildenafil 20mg TID for 4 weeks and placebo (lactose) TID for 4 weeks in a crossover fashion with a 2 week washout period between treatments.
Primary purpose: TREATMENT

Brief summary: The goal of this study is to determine whether administration of sildenafil will decrease urine leakage in patients with spinal cord injuries.

Detailed description: Spinal cord injury (SCI) is a devastating condition affecting 291,000 women and men in the US alone. Urinary incontinence (UI) is a common problem in these patients, affecting 52% of the population, with episodes of incontinence occurring daily in 20-27% of affected persons. UI after spinal cord injury (SCI) is a major cause of distress and morbidity amongst patients with SCI, and is associated with decreased quality of life in general, physical, and emotional domains. UI has the undesirable side effects of perineal irritation and infection, increased odor, disrupted sleep, embarrassment, need to change clothes/bedding, and sexual dysfunction, as well as significant financial burden. Persons living with a SCI have ranked urinary problems as the most important health problem after injury. Addressing this significant problem and providing relief has the potential to significantly improve the lives of patients with SCI.

Typical treatment options are geared toward the type of UI in each patient. For stress UI, the goal of treatment is to provide support to the pelvic floor and urethra. Pessaries (devices placed inside the vagina in women) or surgery (e.g. suburethral sling) to elevate the urethra and/or bladder neck to increase the resistance to leak through the urethra are commonly used. Urethral bulking agents or pelvic muscle floor therapy are also employed to strengthen the closure pressure of the urethra in patients with stress UI. No pharmacologic agents are currently available to treat stress UI. For urge UI, medications or electrical stimulation aimed at relaxation of the detrusor muscle, including anticholinergics, are used. For overflow or obstructive UI, treatments are aimed at shrinking or removing the obstruction, such as medications to shrink the prostate, prostatectomy or mass removal. For neurogenic UI, surgery for diversion or implant placement may be utilized.

Sildenafil (Viagra) has been well studied and used extensively in males to treat erectile dysfunction. Phosphodiesterase 5 (PDE5) inhibitors, including sildenafil, are potent vasodilators that enhance tissue perfusion, relax smooth muscle of the vasculature and bladder, and stimulate skeletal muscle protein synthesis. It has been reported to improve lower urinary tract symptoms, including urge UI and benign prostatic hyperplasia (BPH) in men. In our team's recent study using sildenafil for treatment of UI in women, the investigators found improvement in quality of life and a decrease in the number of incontinence episodes in women taking sildenafil. Higher sildenafil plasma levels were associated with greater improvement in symptoms. While the types of UI in women are somewhat different than in men, studies have shown improvements in UI in both sexes.

Thus, the investigators propose to conduct a two month randomized, placebo-controlled crossover trial of sildenafil in male and female adult SCI patients with UI to assess the therapeutic potential of sildenafil to reduce the symptoms of urinary leakage.

Aims:

Aim 1: To determine whether sildenafil will decrease episodes of leakage of UI in adult women and men with SCI.

Aim 2: To determine the effects of sildenafil on the subjective measures of UI, including quality of life.

Experimental Protocol:

Investigators will study patients with spinal cord injuries (aged 18-70) with current urine leakage of more than 3 times/week (n=24). Subjects will undergo a double blinded randomized cross over treatment of sildenafil (20mg TID) and placebo. Each treatment period will last 4 weeks with a 2 week washout between treatment periods.

Before and after each treatment period, subjects will undergo testing which will consist of measurements of urine post void residual volume (PVR), adverse event assessment, and questionnaires of quality of life and urinary health.

Eligibility criteria: Inclusion Criteria:

* Adults with spinal cord injury (SCI), 18-75 years of age, at the time of consent
* Have urinary incontinence (UI), with at least 3 leakage episodes/week
* Have urodynamics assessment on file with their provider in past 3 years. If no historical data on file, subject may complete prior to study visit 1.
* Willing and able to comply with study procedures
* Willing and able to provide written informed consent

Exclusion Criteria:

* In phone prescreen, delighted or pleased with current quality of life due to urinary symptoms.
* Indwelling catheter
* History of greater than 4 urinary tract infections per year
* Multiple sclerosis
* Significant heart, liver, kidney, pulmonary, blood, autoimmune or peripheral vascular disease
* Systolic blood pressure \<90 or \>170, diastolic blood pressure \<50 or \>110 after repeated evaluation with proper cuff. This range is the acceptable range stated in the prescribing information for sildenafil (\>90/50 and \<170/110)
* Active cancer
* HIV, Hepatitis B, or Hepatitis C
* Use of systemic nitrates, anabolic steroids, corticosteroids, or long acting PDE5 inhibitors in the past 1 month
* Use of short acting PDE5 inhibitors in the past 1 week
* Use of alpha blockers, anticholinergic agents, bethanechol, or other UI treatment within the past 2 weeks ( 3 weeks for long acting muscarinic receptor antagonists)
* Known allergic reaction to any agent under investigation or required by the protocol
* Females who are pregnant or lactating
* Atonic bladder or high detrusor and high pelvic floor muscle pressure based on previous cystometrogram (CMG) (on file with their provider) that would place subjects at risk for kidney injury
* Any medical condition that, in the opinion of the investigator, would place the subject at increased risk for participation

Primary outcomes:
measure: Bladder Leakage as measured by 5 day bladder diary at Baseline
timeFrame: baseline
measure: Bladder Leakage as measured by 5 day bladder diary after 4 weeks of Sildenafil Treatment
timeFrame: after 4 weeks of sildenafil treatment
measure: Bladder Leakage as measured by 5 day bladder diary after 4 weeks of Placebo Treatment
timeFrame: after 4 weeks of placebo treatment
Secondary outcomes:
measure: Blood sildenafil levels as measured by Liquid Chromatography Mass Spectrometry (LCMS) at baseline
timeFrame: baseline
measure: Blood sildenafil levels as measured by Liquid Chromatography Mass Spectrometry (LCMS) after 4 weeks of sildenafil treatment
timeFrame: after 4 weeks of sildenafil treatment
measure: Blood sildenafil levels as measured by Liquid Chromatography Mass Spectrometry (LCMS) after 4 weeks of placebo treatment
timeFrame: after 4 weeks of placebo treatment
measure: Post void residual urine volume as measured by ultrasound bladder scanner at baseline
timeFrame: baseline
measure: Post void residual urine volume as measured by ultrasound bladder scanner after 4 weeks of sildenafil treatment
timeFrame: after 4 weeks of sildenafil treatment
measure: Post void residual urine volume as measured by ultrasound bladder scanner after 4 weeks of placebo treatment
timeFrame: after 4 weeks of placebo treatment
measure: Urinary symptoms as measured by the American Urological Association Symptom Score at baseline
timeFrame: baseline
measure: Urinary symptoms as measured by the American Urological Association Symptom Score after 4 weeks of sildenafil treatment
timeFrame: after 4 weeks of sildenafil treatment
measure: Urinary symptoms as measured by the American Urological Association Symptom Score after 4 weeks of placebo treatment
timeFrame: after 4 weeks of placebo treatment
measure: Bladder dysfunction as measured by the Neurogenic Bladder Symptom Score at baseline
timeFrame: baseline
measure: Bladder dysfunction as measured by the Neurogenic Bladder Symptom Score after 4 weeks of sildenafil treatment
timeFrame: after 4 weeks of sildenafil treatment
measure: Bladder dysfunction as measured by the Neurogenic Bladder Symptom Score after 4 weeks of placebo treatment
timeFrame: after 4 weeks of placebo treatment
measure: Perception of bladder conditions as measured by the Patient Perception of Bladder Symptoms questionnaire at baseline
timeFrame: baseline
measure: Perception of bladder conditions as measured by the Patient Perception of Bladder Symptoms questionnaire after 4 weeks of sildenafil treatment
timeFrame: after 4 weeks of sildenafil treatment
measure: Perception of bladder conditions as measured by the Patient Perception of Bladder Symptoms questionnaire after 4 weeks of placebo treatment
timeFrame: after 4 weeks of placebo treatment
measure: Urinary Symptoms Interference as measured by Pelvic Floor Impact Questionnaire at baseline
timeFrame: baseline
measure: Urinary Symptoms Interference as measured by Pelvic Floor Impact Questionnaire after 4 weeks of sildenafil treatment
timeFrame: after 4 weeks of sildenafil treatment
measure: Urinary Symptoms Interference as measured by Pelvic Floor Impact Questionnaire after 4 weeks of placebo treatment
timeFrame: after 4 weeks of placebo treatment
Other outcomes:
Locations:
city: College Station
country: United States
facility: Texas A&M University
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: University of Texas
name: Kathy Vincent, MD
role: PRINCIPAL_INVESTIGATOR
References: