Effect of Botulinum Toxin A on Detrusor Overactivity and Renal Function in Chronic Spinal Cord Injured Patients
Condition: Spinal Cord Injuries
MeSH terms: Spinal Cord Injuries
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Botulinum toxin A
Intervention type(s): Drug
Intervention description(s): BoNT-A (BOTOX 300U)
Other intervention name(s): BoNT-A (BOTOX 300U)
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Nerve growth factor; P2X3 receptor; Transient Receptor Potential Vanilloid 1 (TRPV-1) receptor; Bladder function; Glomerular filtration rate; Detrusor overactivity; Spinal cord injury