Intravesical Instillation of Liposome Encapsulated Botulinum Toxin A (Lipotoxin) in Treatment of Interstitial Cystitis - a Randomized, Double-blind, Placebo-controlled, Prospective Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change of the O'Leary-Sant symptom score
研究概览
简要总结
To evaluate the efficacy and safety of intravesical instillation of Lipotoxin for the treatment of IC/BPS
详细描述
Liposome has been proven able to carry botulinum toxin protein across the cell membrane and effect on urothelial receptors in human overactive bladder. However, the therapeutic duration is limited to 1 month. Intravesical BOTOX injection in patients with interstitial cystitis (IC) can effectively decrease pain, improve bladder capacity and decrease frequency. However, the need of cystoscopic injection limits its wide application.
A total of 100 eligible women with non-ulcer IC will be enrolled to receive intravesical instillation of Lipotoxin containing 80mg liposomes and 200U BOTOX (treatment group), 200U BOTOX in normal saline (N/S) (active control group) or normal saline (placebo control group) single treatment. At least 90 evaluable patients will be included for the final analysis.
All patients should have IC symptoms for at least 6 months, and proven to have grade 2 diffused glomerulations after cystoscopic hydrodistention (HD) within recent 1 year without Hunner's lesion. Patients should not have UTI in recent 12 months, no urinary tract stone. Patients should have been proven free of detrusor overactivity or bladder outlet obstruction. Patients should not receive intravesical hyaluronic acid treatment in recent 6 months, or intravesical Botox injection in recent 12 months. Intravesical instillation of Lipotoxin at OPD and the patient should hold the solution for 2 hours to allow bladder distention. Retreatment with Lipotoxin at 3 months if patient reports ineffective.
Primary end-point is the change of the O'Leary-Sant symptom score (including ICSI and ICPI) from baseline to 1 month after treatment. Secondary endpoints include VAS, daily frequency, nocturia and FBC as record in 3-day voiding diary, Qmax, voided volume, PVR and global response assessment (GRA). Four visits are required at baseline screening (before first treatment), treatment (V1), 2 weeks (V2), 4 weeks (V3, primary end-point) and 12 weeks (V4).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
All participants, investigators and care providers do not know which regimen is given to patients of the three arms.
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults with age of 20 years old or above
- •Patients with symptoms of frequency, urgency, nocturia, and/or bladder pain.
- •Proven to have glomerulations (at least grade 2) by cystoscopic hydrodistention under anesthesia in recent 1 year
- •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
排除标准
- •Hunner's lesion proven by cystoscopy
- •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 postvoid residual >250ml
- •Patients with uncontrolled confirmed diagnosis of acute urinary tract infection
- •Patients have laboratory abnormalities at screening including: ALT> 3 x upper limit of normal range, AST> 3 x upper limit of normal range; Patients have abnormal serum creatinine level > 2 x upper limit of normal range
- •Patients with any contraindication to be urethral catheterization during treatment
- •Female patients who is pregnant, lactating, or with child-bearing potential without contraception.
- •Myasthenia gravis, Eaton Lambert syndrome.
- •Patients with any other serious disease considered by the investigator not in the condition to enter the trial
- •Patient had received intravesical treatment for IC within recent 1 month
- •Patients participated investigational drug trial within 1 month before entering this study
研究组 & 干预措施
Group A: Liposome encapsulated BoNT-A
Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation
干预措施: Liposome encapsulated BoNT-A (Drug)
Group B: BoNT-A 200 U in Normal saline
BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation
干预措施: BOTOX 200U in normal saline (Drug)
Group C: Normal saline
Normal saline (N/S) 50ml in single intravesical instillation
干预措施: Normal saline (Drug)
结局指标
主要结局
Change of the O'Leary-Sant symptom score
时间窗: Baseline and 1 month
Change of the O'Leary-Sant symptom score from baseline to 1 month after the treatment day
次要结局
- Net Change of the voided volume(Baseline and 1 month)
- Net Change of the PVR(Baseline and 1 month)
- Net changes of the voiding frequency at night time as recorded in 3-day voiding diary(Baseline and 1 month)
- Net changes of the Visual Analog Scale (VAS)(Baseline and 1 month)
- Net changes of the functional bladder capacity (FBC)(Baseline and 1 month)
- Net Change of the Global response assessment (GRA)(Baseline and 1 month)
- Net Change of the maximum flow rate(Baseline and 1 month)
- Net Change of the urinary nerve growth factor(Baseline and 1 month)
- Net Change of the cytokines level(Baseline and 1 month)
- Net changes of the voiding frequency at daytime as recorded in 3-day voiding diary(Baseline and 1 month)
研究者
Hann-Chorng Kuo
Director of Urology
Buddhist Tzu Chi General Hospital