Ignite Creation Date:
2025-12-24 @ 7:45 PM
Ignite Modification Date:
2025-12-29 @ 7:46 PM
Study NCT ID:
NCT01682603
Status:
COMPLETED
Last Update Posted:
2017-03-20
First Post:
2012-09-07
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effect of Botulinum Toxin A on Detrusor Overactivity and Renal Function in Chronic Spinal Cord Injured Patients
Sponsor:
Buddhist Tzu Chi General Hospital
Organization:
Study Overview
Official Title:
Effect of Botulinum Toxin A on Detrusor Overactivity and Renal Function in Chronic Spinal Cord Injured Patients - Clinical Effects and Investigating Mechanism of Action
Status:
COMPLETED
Status Verified Date:
2014-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To investigate the clinical effect of detrusor botulinum toxin A (BoNT-A) injection on neurogenic detrusor overactivity (NDO) and renal function and to compare the difference of expressions of sensory receptors and nerve growth factor (NGF) in the bladder wall of patients respond and not respond to BoNT-A injections in chronic spinal cord injured (SCI) patients.
Detailed Description:
Study Procedure
A total of 30 patients with chronic suprasacral cord SCI will be enrolled in this study. All patients are more than 18 years old and have chronic suprasacral cord injury for more than 1 year. They have previously underwent an urodynamic study and have been proven having detrusor sphincter dyssynergia (DSD). The patients currently void by reflex, abdominal stimulation or clean intermittent catheterization (CIC), are free of indwelling catheter or cystostomy, and free of urinary tract infection (UTI) on their enrollment. During the screening period, a total glomerular filtration rate (GFR) should be less than 80 mL/min as measured by 99mTc-labelled diethylenetriamine pentaacetic acid (99mTc-DTPA) clearance renal scanning. Patients should also have adequate hand function or have a care-giver available for CIC. Other exclusion criteria include patients with detrusor underactivity and large bladder compliance, patients proven to have intrinsic sphincteric deficiency and patients who have hypersensitivity to botulinum toxin A (BTX-A) or constituent ingredients of BTX-A.
BTX-A injection will be performed in the operation room under light intravenous general anesthesia to prevent autonomic dysreflexia and hyperreflexia during cystoscopy. A total of 300U BTX-A (BOTOX, 100 U/vial, Allergan Co., Irvine, USA) dissolved into 30 mL normal saline will be injected into 30 sites of the bladder including lateral, posterior wall and dome. The injection sites are widely distributed to cover the whole bladder wall. A 14 Fr Foley catheter will be routinely inserted after BTX-A injection and patients will be discharged the next morning and followed up at out-patient clinic. All patients will be instructed to keep on CIC or abdominal stimulation as they previously performed. BTX-A injections will be repeated 6 months after the first treatment, then follow up to 24 months. Before each BTX-A injection a videourodynamic study and GFR test will be performed. Patients were also requested to report the severity of urinary incontinence by the mean daily incontinence episodes within three days, Urogenital Distress Inventory (UDI-6 Short Form), Incontinence Impact Questionnaire (IIQ-7), self assessed QoL index and the global satisfaction rate (graded as 0 to 3, indicating none, mild, moderate and very satisfied) to this treatment. The adverse events such as urinary tract infection, hematuria, difficult urination are also recorded.
This study should be approved by the Institutional Review Board and Ethics Committee of the hospital. Informed consent will be obtained before the screening and all patients are instructed about the possible complications related with BTX-A injection such as urinary retention, transient hematuria and subsequent urinary tract infection.
Patients will be classified as responders and non-responders according to their clinical presentation and urodynamic study results. Responders are considered if they become dry or reduction of incontinence episodes by 50% and have a decrease of detrusor pressure reduction by 50% of the baseline value, otherwise, they are considered as non-responders. The end-point is set at 6 months after the BTX-A injection.
There were two primary end-points: (1) the net change of the IIQ-7 and UDI-6 from baseline to 24 months, and (2) the net change of the GFR from baseline to 24 months. Secondary end-point efficacy measured the net change of the cystometric bladder capacity, bladder compliance, detrusor pressure during reflex voiding, end-filling pressure or detrusor leak-point pressure and postvoid residual volume from baseline to 24 months.
Three bladder biopsies using a small cystoscopic biopsy forceps will be performed in all patients. The biopsy will be performed at baseline and each time-point just prior to intravesical BTX-A injection. The bladder biopsy specimens will be sent to pathological department for H-E staining to exclude the possibility of carcinoma in situ, and also will be embedded in O.C.T. medium and stored at -80℃ refrigerator or liquid nitrogen tank for investigations. The bladder biopsies will be prepared for measurement of NGF messenger RNA (mRNA) and immunohistochemistry investigation of the expression of Transient Receptor Potential Vanilloid 1 (TRPV-1), purinergic receptor P2X, ligand-gated ion channel, 3 (P2X3) receptors at baseline and 6 months after each BTX-A injection, and the difference of these sensory protein expressions between responders and .non-responders to BTX-A injection.
A total of 30 patients with chronic suprasacral cord SCI will be enrolled in this study. All patients are more than 18 years old and have chronic suprasacral cord injury for more than 1 year. They have previously underwent an urodynamic study and have been proven having detrusor sphincter dyssynergia (DSD). The patients currently void by reflex, abdominal stimulation or clean intermittent catheterization (CIC), are free of indwelling catheter or cystostomy, and free of urinary tract infection (UTI) on their enrollment. During the screening period, a total glomerular filtration rate (GFR) should be less than 80 mL/min as measured by 99mTc-labelled diethylenetriamine pentaacetic acid (99mTc-DTPA) clearance renal scanning. Patients should also have adequate hand function or have a care-giver available for CIC. Other exclusion criteria include patients with detrusor underactivity and large bladder compliance, patients proven to have intrinsic sphincteric deficiency and patients who have hypersensitivity to botulinum toxin A (BTX-A) or constituent ingredients of BTX-A.
BTX-A injection will be performed in the operation room under light intravenous general anesthesia to prevent autonomic dysreflexia and hyperreflexia during cystoscopy. A total of 300U BTX-A (BOTOX, 100 U/vial, Allergan Co., Irvine, USA) dissolved into 30 mL normal saline will be injected into 30 sites of the bladder including lateral, posterior wall and dome. The injection sites are widely distributed to cover the whole bladder wall. A 14 Fr Foley catheter will be routinely inserted after BTX-A injection and patients will be discharged the next morning and followed up at out-patient clinic. All patients will be instructed to keep on CIC or abdominal stimulation as they previously performed. BTX-A injections will be repeated 6 months after the first treatment, then follow up to 24 months. Before each BTX-A injection a videourodynamic study and GFR test will be performed. Patients were also requested to report the severity of urinary incontinence by the mean daily incontinence episodes within three days, Urogenital Distress Inventory (UDI-6 Short Form), Incontinence Impact Questionnaire (IIQ-7), self assessed QoL index and the global satisfaction rate (graded as 0 to 3, indicating none, mild, moderate and very satisfied) to this treatment. The adverse events such as urinary tract infection, hematuria, difficult urination are also recorded.
This study should be approved by the Institutional Review Board and Ethics Committee of the hospital. Informed consent will be obtained before the screening and all patients are instructed about the possible complications related with BTX-A injection such as urinary retention, transient hematuria and subsequent urinary tract infection.
Patients will be classified as responders and non-responders according to their clinical presentation and urodynamic study results. Responders are considered if they become dry or reduction of incontinence episodes by 50% and have a decrease of detrusor pressure reduction by 50% of the baseline value, otherwise, they are considered as non-responders. The end-point is set at 6 months after the BTX-A injection.
There were two primary end-points: (1) the net change of the IIQ-7 and UDI-6 from baseline to 24 months, and (2) the net change of the GFR from baseline to 24 months. Secondary end-point efficacy measured the net change of the cystometric bladder capacity, bladder compliance, detrusor pressure during reflex voiding, end-filling pressure or detrusor leak-point pressure and postvoid residual volume from baseline to 24 months.
Three bladder biopsies using a small cystoscopic biopsy forceps will be performed in all patients. The biopsy will be performed at baseline and each time-point just prior to intravesical BTX-A injection. The bladder biopsy specimens will be sent to pathological department for H-E staining to exclude the possibility of carcinoma in situ, and also will be embedded in O.C.T. medium and stored at -80℃ refrigerator or liquid nitrogen tank for investigations. The bladder biopsies will be prepared for measurement of NGF messenger RNA (mRNA) and immunohistochemistry investigation of the expression of Transient Receptor Potential Vanilloid 1 (TRPV-1), purinergic receptor P2X, ligand-gated ion channel, 3 (P2X3) receptors at baseline and 6 months after each BTX-A injection, and the difference of these sensory protein expressions between responders and .non-responders to BTX-A injection.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: