Botulin-A Toxin/Dimethyl Sulfoxide Bladder Instillations for Treatment of Voiding Dysfunction Secondary to Detrusor Hyperreflexia and Detrusor Instability in Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Median Number of Incontinent Episodes During 24 Hours
研究概览
简要总结
The primary objective of this pilot study is to evaluate the safety and efficacy of direct instillations of Botulinum-A toxin/DMSO into the bladder via a catheter system as a means of treating women with symptoms of overactive bladder and secondary urinary incontinence. In doing so, we will focus on estimating the percentage of women who experience an improvement in their urinary incontinence symptoms at one month and three months following this novel instillation technique.
详细描述
Rationale:
To date, the standard treatment for overactive bladder (including detrusor hyperreflexia and detrusor overactivity) consists of oral anticholinergic medications that can have troublesome side effects and variable efficacy. What's more, patients failing pharmacological therapy must either live with their malady or undergo open surgery that is irreversible and carries a prolonged convalescence. The fact remains however that treatment for overactive bladder is necessary to help maintain quality of life and prevent upper urinary tract deterioration. In recent years, cystoscopic-guided injection of Botulinum-A toxin has been used as a novel method of addressing detrusor hyperreflexia and overactivity by blocking acetylcholine transmission at the bladder. The obvious benefits of a more targeted therapy notwithstanding, this method requires the use of a cystoscope, needle delivery of the agent through approximately 30 separate injection sites and either regional or topical intravesical anesthesia for peri-operative pain control. Clearly, the identification of less invasive and more cost effective means of delivering the beneficial effects of Botulinum-A toxin to the bladder muscle has the potential to enhance the overall appeal of this treatment method.
Objectives:
The primary objective of this pilot study is to evaluate the safety and efficacy of direct instillations of Botulinum-A toxin/DMSO into the bladder via a catheter system as a means of treating women with symptoms of overactive bladder and secondary urinary incontinence. In doing so, we will focus on estimating the percentage of women who experience an improvement in their urinary incontinence symptoms at one month and three months following this novel instillation technique.
Study Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patient aged 18 years or older
- •Patient with a history of stress urinary incontinence for at least 12 months
- •Patient with Intrinsic Sphincter Deficiency who demonstrate an abdominal leak point pressure of less than 100 cm of water on urodynamic evaluation
- •Patient with urinary incontinence verified by the Provocation test: a mean urinary leakage of 10 g on screening and baseline visits
- •Patient with positive stress test and/or urodynamic stress incontinence
- •Patient who has failed prior non-invasive treatment (e.g. behavior modification, pelvic floor exercises, biofeedback, electrical stimulation and/or drug therapy)
- •Patient with negative Contigen skin test during screening.
- •Patient who is mentally competent with the ability to understand and comply with the requirements of the study
- •Patient who agrees to be available for the follow-up evaluations as required by the protocol
- •Patient who has given signed informed consent
排除标准
- •Patient with Q-tip angle greater than 30 degrees
- •Patient with Functional Bladder capacity <200 ml as recorded in the baseline Bladder Diary
- •Patient with Post-Void Residual Urine (PVRU) greater than 100 ml on repeated measures. (Patient with a single PVRU of >100 ml and followed by two consecutive PVRU measurements of <100 ml may be included in the study)
- •Patient with vesicoureteral reflux, interstitial cystitis, genitourinary fistulae
- •Patient with predominant urge incontinence
- •Patient with detrusor overactivity on filling cystometry
- •Patient with pelvic organ prolapse stage III or IV, i.e. the most distal part of the prolapse protruding more than 1 cm beyond the hymen (>+1), at straining
- •Patient with urinary incontinence due to neurological disease that is known to affect urinary tract infection
- •Patient with uninvestigated hematuria
- •Patient with genitourinary malignancies
- •Patient on current medication for stress urinary incontinence, such as alpha-adrenergic agonists or duloxetine, within three weeks prior to completing the baseline Bladder Diary (estrogen therapy on a stable dose for at least two months prior to study start is allowed)
- •Patient who has had bulking therapy for stress urinary incontinence
- •Patient with ongoing complications of prior anti-incontinence surgery
- •Patient who is pregnant, lactating, or planning to become pregnant within the study period
- •Patient who has received pelvic radiation
- •Patient with any condition, which could lead to significant postoperative complications, including current infection and uncontrolled diabetes.
- •Patient who is morbidly obese (defined as BMI > 32 Kg/m2)
- •Patient who is bedridden, institutionalized or in such physical condition that she cannot move to the closest bathroom without assistance from another person
- •Patient with current or acute urinary tract infection, including cystitis or urethritis. (Patient with such infections should be treated with antibiotics, with subsequent urinalysis tests confirming the absence of such infection before study inclusion)
- •Patient with any condition that would preclude treatment due to contraindications and/or warnings in the study product's labeling
- •Patient on concomitant medication with anticoagulant properties (e.g., Warfarin, Heparin, Aspirin, Nonsteroidal anti-inflammatory drugs (NSAIDs), except for cox-2 inhibitors) within two weeks prior to treatment
- •Patient on immunomodulatory therapy (suppressive or stimulatory)
- •Patient with a known allergy to bovine collagen
- •Patient with known lidocaine hypersensitivity or hypersensitivity to any anesthetics to be used during the treatment session/surgical procedure
- •Patient with a concurrent use of another study product within two weeks prior to study start, or who concurrently participate in any other clinical study
- •Any disease that in the opinion of the Investigator would make the patient unsuitable for the study
- •Patient with a life expectancy of less than 12 months
研究组 & 干预措施
Botox/DMSO Solution
Subjects received Botulinum-A toxin and Dimethyl sulfoxide solution. The first 3 subjects in Phase 1 underwent bladder instillation of 50 cc of the solution utilizing 200 units of botulinum-A toxin and 50cc DMSO. The next 6 subjects in the Phase 1 trial received 300 units of botulinum-A toxin and 50cc DMSO.
All subjects in the Phase 2 trial received 300 units of botulinum-A toxin and 50cc DMSO.
干预措施: Botulinum-A toxin (Drug)
Botox/DMSO Solution
Subjects received Botulinum-A toxin and Dimethyl sulfoxide solution. The first 3 subjects in Phase 1 underwent bladder instillation of 50 cc of the solution utilizing 200 units of botulinum-A toxin and 50cc DMSO. The next 6 subjects in the Phase 1 trial received 300 units of botulinum-A toxin and 50cc DMSO.
All subjects in the Phase 2 trial received 300 units of botulinum-A toxin and 50cc DMSO.
干预措施: Dimethyl sulfoxide (DMSO) (Drug)
结局指标
主要结局
Median Number of Incontinent Episodes During 24 Hours
时间窗: baseline, 1 month, 3 months
The study coordinator instructed the subject to keep record of any incontinence episodes during the 24-hour period prior to their baseline and follow-up visits.
次要结局
- Incontinence Impact Questionnaire-short Form (IIQ-7) Scores(baseline, 1 month, 3 months)
- Urinary Urgency at 3 Months(3 months after treatment)
- Median 24 Hour Pad Weight(baseline, 1 month, 3 months)
- Blaivas-Groutz Anti-Incontinence Score at Baseline(baseline)
- Bothersomeness(baseline, 1 month, 3 months)
- Blaivas-Groutz Anti-Incontinence Score at 1 Month(1 month after treatment)
- Blaivas-Groutz Anti-Incontinence Score at 3 Months(3 months after treatment)
- Mean Number of Pads Per Day(baseline, 1 month, 3 months)
- Postvoid Residual(baseline, 1 month, 3 months)
- Urine Culture(baseline, 1 month, 3 months)
- Urinary Urgency at Baseline(baseline)
- Urinary Urgency at 1 Month(1 month after treatment)
- Median Urogenital Distress Inventory (UDI-6) Scores(baseline, 1 month, 3 months)