Efficacy and Tolerability of Mirabegron Compared to Oxybutynin Chloride Immediate Release for Neurogenic Detrusor Overactivity in Persons With Chronic Spinal Cord Injury: A Randomized, Double-Blind, Controlled, Cross-Over Clinical Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Change in cystometric bladder capacity during filing cystometry
研究概览
简要总结
The purpose of this research study is to determine the effectiveness and safety of mirabegron compared to oxybutynin chloride immediate release (oxybutynin IR) for a condition called neurogenic detrusor overactivity in individuals with chronic spinal cord injury (SCI).
详细描述
Neurogenic detrusor overactivity or "NDO" is common in people with spinal cord injury (SCI) and is a medical condition characterized by involuntary urinary bladder contractions. These bladder contractions can cause episodes of urinary incontinence (involuntary urine leakage) and/or high bladder pressures that can lead to poor drainage from the kidneys and urinary tract infections (UTIs).
Neurogenic detrusor overactivity is most commonly treated with a medication called oxybutynin (Ditropan); however, this medication is associated with side effects such as dry mouth and constipation. Mirabegron (Myrbetriq) is a newer medication approved by the Food and Drug Administration for the treatment of overactive bladder that does not cause dry mouth or constipation; however, its use in persons with SCI is investigational.
The purpose of this research study is to determine the effectiveness and safety of mirabegron compared to oxybutynin chloride immediate release (oxybutynin IR) for neurogenic detrusor overactivity in individuals with SCI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All study investigators, participants, and assessors will be blind to group assignment. Blinding code will only be broken in emergency situations for reasons of subject safety, where knowledge of the treatment administered is necessary for the treatment of the adverse event under Good Clinical Practices (GCPs), or when required by local regulatory authorities.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject has a neurological impairment secondary to a traumatic spinal cord injury that occurred at least twelve (12) months prior to the screening visit.
- •The injury is classified as complete or incomplete (AIS grade A-D) and the neurological level of the injury is above T
- •The subject's method of bladder management is intermittent catheterization (IC) or indwelling catheter (transurethral or suprapubic).
- •There is urodynamic documentation of neurogenic detrusor overactivity (NDO).
- •The subject is on a stable dose of oxybutynin IR three times daily.
- •The subject is able and willing to comply with the study protocol, including availability for all scheduled clinic visits and locomotor training sessions.
- •The subject is able to and has voluntarily given informed consent prior to the performance of any study-specific procedures.
排除标准
- •The subject has taken mirabegron within one month of the Screening Visit.
- •The subject has received a botulinum toxin injection to the bladder within one year of the Screening Visit.
- •The subject is allergic to mirabegron.
- •The subject has a history of uncontrolled autonomic dysreflexia or significant autonomic dysreflexia on urodynamics (systolic BP≥150 mm/Hg).
- •The subject has a known history of significant anatomical problems of the upper tracts, including hydronephrosis, kidney stones, or ureteropelvic junction obstruction.
- •The subject has a known history or treatment for a non-neurogenic bladder or prostate problem (prostate cancer, bladder cancer).
- •The subject has recurrent UTIs, defined as a UTI more than every three months.
- •The subject has untreated Grade 3 or above vesicoureteral reflux.
- •If female, the subject is pregnant (documented by a urine pregnancy test) or breastfeeding.
- •The subject has taken another investigational drug within 30 days before screening.
- •The subject has a medical condition that might pose a safety issue or would interfere with interpretation of study results or study conduct.
研究组 & 干预措施
Oxybutynin chloride IR then Mirabegron
Subjects randomized to this group will receive oxybutynin IR (5 mg three times daily) for 6 weeks. After the initial 6 weeks, subjects in this group will then be switched to an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily).
干预措施: Oxybutynin Chloride IR (Drug)
Oxybutynin chloride IR then Mirabegron
Subjects randomized to this group will receive oxybutynin IR (5 mg three times daily) for 6 weeks. After the initial 6 weeks, subjects in this group will then be switched to an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily).
干预措施: Mirabegron (Drug)
Mirabegron then Oxybutynin chloride IR
Subjects randomized to this group will receive an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily). After the initial 6 weeks, subjects in this group will then be switched to receive oxybutynin IR (5 mg three times daily) for 6 weeks
干预措施: Oxybutynin Chloride IR (Drug)
Mirabegron then Oxybutynin chloride IR
Subjects randomized to this group will receive an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily). After the initial 6 weeks, subjects in this group will then be switched to receive oxybutynin IR (5 mg three times daily) for 6 weeks
干预措施: Mirabegron (Drug)
结局指标
主要结局
Change in cystometric bladder capacity during filing cystometry
时间窗: Week 6 and Week 12
The cystometric bladder capacity is the bladder volume (ml) at the end of the filling cystometrogram, when 'permission to void' is usually given.
次要结局
- Change in detrusor leak point pressure(Week 6 and Week 12)
- Change in maximum detrusor pressure(Week 6 and Week 12)
- Change in bladder compliance during filling cystometry(Week 6 and Week 12)
- Change in post-void residual volume(Week 6 and Week 12)
- Change on International Lower Urinary Tract Function Basic Spinal Cord Injury (SCI) Data Set(Week 6 and Week 12)
- Change on Bowel Function Measures - International SCI Bowel Function Basic & Extended Data Sets(Week 6 and Week 12)
- Change in California Verbal Learning Test - II (CVLT) scores(Week 6 and Week 12)
- Change in Symbol Digit Modalities Test oral version (SDMT) scores(Week 6 and Week 12)
- Wechsler Test of Adult Reading (WTAR) score(Screening Visit)
- Change in Qualiveen scores(Week 6 and Week 12)
- Change in SCI-QOL Bowel & Bladder Management Difficulties scores(Week 6 and Week 12)
- Change in Subject Global Impression (SGI) of Change score(Week 6 and Week 12)
- Change in Clinician Global Impression (CGI) of Change score(Week 6 and Week 12)
研究者
Trevor Dyson-Hudson, M.D.
Director, Spinal Cord Injury Research
Kessler Foundation