Intravesical Instillation of Liposome Encapsulated Botulinum Toxin A (Lipotoxin) in Treatment of Interstitial Cystitis

Interstitial Cystitis Clinical Trial

Official title:

Intravesical Instillation of Liposome Encapsulated Botulinum Toxin A (Lipotoxin) in Treatment of Interstitial Cystitis — a Randomized, Double-blind, Placebo-controlled, Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02247557
• Other study ID #: TCGHUROL011
• Status: Completed
• Phase: Phase 2
• First received: September 15, 2014
• Last updated: March 7, 2017
• Start date: September 2014
• Est. completion date: February 2017

Study information

• Verified date: March 2017
• Source: Buddhist Tzu Chi General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy and safety of intravesical instillation of Lipotoxin for the treatment of IC/BPS

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Adults with age of 20 years old or above

2. Patients with symptoms of frequency, urgency, nocturia, and/or bladder pain.

3. Proven to have glomerulations (at least grade 2) by cystoscopic hydrodistention under anesthesia in recent 1 year

4. Free of active urinary tract infection

5. Free of bladder outlet obstruction on enrollment

6. Free of overt neurogenic bladder dysfunction and limitation of ambulation

7. Patient or his/her legally acceptable representative has signed the written informed consent form

Exclusion Criteria:

1. Hunner's lesion proven by cystoscopy

2. Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up

3. Patients with bladder outlet obstruction on enrollment

4. Patients with postvoid residual >250ml

5. Patients with uncontrolled confirmed diagnosis of acute urinary tract infection

6. 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

7. Patients with any contraindication to be urethral catheterization during treatment

8. Female patients who is pregnant, lactating, or with child-bearing potential without contraception.

9. Myasthenia gravis, Eaton Lambert syndrome.

10. Patients with any other serious disease considered by the investigator not in the condition to enter the trial

11. Patient had received intravesical treatment for IC within recent 1 month

12. Patients participated investigational drug trial within 1 month before entering this study

Related Conditions & MeSH terms

• Cystitis
• Cystitis, Interstitial
• Interstitial Cystitis

Intervention

Drug:
• Liposome encapsulated BoNT-A
Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation
• BOTOX 200U in normal saline
BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation
• Normal saline
Normal saline (N/S) 50ml in single intravesical instillation

Locations

Country	Name	City	State
Taiwan	Buddhist Tzu Chi General Hospital	Hualien

Sponsors (1)

Lead Sponsor	Collaborator
Buddhist Tzu Chi General Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of the O'Leary-Sant symptom score	Change of the O'Leary-Sant symptom score from baseline to 1 month after the treatment day	Baseline and 1 month
Secondary	Net changes of the Visual Analog Scale (VAS)	Net changes of the Visual Analog Scale from baseline to 1 month after the treatment day; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net changes of the functional bladder capacity (FBC)	Net changes of the functional bladder capacity from baseline to 1 month after the treatment day; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net changes of the voiding frequency at daytime as recorded in 3-day voiding diary	Net changes of the voiding frequency at daytime from baseline to 1 month after the treatment day; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net changes of the voiding frequency at night time as recorded in 3-day voiding diary	Net changes of the voiding night time from baseline to 1 month after the treatment day; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net Change of the Global response assessment (GRA)	Global response assessment (GRA) of therapeutic result by the patient (categorized from -3 to +3, indicating markedly worse to markedly improved) at 3 months after the treatment day.; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net Change of the maximum flow rate	Net changes of the maximum flow rate from baseline to 1 month after the treatment day.; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net Change of the voided volume	Net changes of the voided volume from baseline to 1 month after the treatment day.; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net Change of the PVR	Net changes of the PVR from baseline to 1 month after the treatment day.; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net Change of the urinary nerve growth factor	Changes of urinary nerve growth factor from baseline to 1 month after treatment day.; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month
Secondary	Net Change of the cytokines level	Changes of cytokines level from baseline to 1 month after treatment day.; Safety; (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).	Baseline and 1 month