Botox-A Injection to Improve Bladder Function in Early Spinal Cord Injury (#H-20344)
Condition: Neurogenic Bladder Dysfunction Nos; Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Urinary Bladder, Neurogenic; Wounds and Injuries
Intervention: BOTOX-A; Saline injection
Intervention description: Group 1-100 units of BTX-A (Botox®, Allergan Inc., Irvine, CA) on Day 0 and 100 units of BTX-A on Day 90; Group 2-sham saline injections on both Day 0 and Day 90.
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Spinal Cord Injury; Bladder; Botulinum toxin (BOTOX-A; Detrusor External Sphincter Dyssynergia

Summary:

      The purpose of this study is to see what the effect of Botox has on bladder function for
      those who have recently suffered spinal cord injury. We also will study bladder tissue levels
      of NGF (nerve growth factor) that can tell us how the nerves to the bladder are healing after
      injury.

      Consenting male and female cervical and high thoracic (T10 and above) SCI patients will be
      identified within the first 6-7 weeks after SCI and randomized to two external urethral
      sphincter injection groups. Each group will be injected within 8 weeks after SCI (Day 0) and
      3 months later (Day 90). The injection paradigm will consist of: Group 1-100 units of BTX-A
      (Botox®, Allergan Inc., Irvine, CA) on Day 0 and 100 units of BTX-A on Day 90; Group 2-sham
      saline injections on both Day 0 and Day 90. Injections will be performed under local
      anesthesia using standard flexible cystoscopic equipment.

      Use of placebo is justified because: 1. there have been documentation of nerve
      desensitization with dry needling (i.e. acupuncture) and wet needling (i.e.
      saline)--therefore, to truly demonstrate benefit of Botox over just the needle insertion into
      the sphincter muscle or injection of the diluent saline, a sham saline injection group is
      included, 2. the injection procedure itself is minimally invasive and not expected to result
      in any complications.

      Subjects who qualify and have signed the informed consent document will be randomized into
      two groups, those receiving the BTX-A and those receiving placebo. Blinding will be performed
      by the TIRR pharmacy department who will provide Botox and placebo in identical syringes so
      that the treating staff will be blinded. Pharmacists will ensure patients receive the same
      agent at the time of the second injection. Unblinding will occur at the end of the study or
      if complications necessitate breaking of the code. Both groups will undergo urodynamic
      testing to document before and after treatment data. Bladder biopsies will be taken prior to
      treatment in both groups that will be analyzed for nerve growth factor. Three day voiding
      diaries will be kept and reviewed with the study coordinator at the follow up visits. Quality
      of life questionnaires will be completed at each follow up visit. The treatments will take
      place on Day 0 and Day 90. Follow up visits will occur at Day 120, 16 month, and 28 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or Females between ages of 18-50

          -  Patient weighs over 111 pounds

          -  Patient has documented Spinal Cord Injury T10 or above Thoracic Level by ASIA Score
             less than 8 weeks prior to the start of the study. Both complete and incomplete spinal
             cord injuries will be included in this study.

          -  Ability to complete all study requirements including voiding diary and to attend all
             scheduled study visits, in the opinion of the investigator

          -  Written informed consent has been obtained

          -  Patient has negative pregnancy test result if female and of child-bearing potential

          -  Written authorization for use and release of Health and Research Study Information has
             been obtained

          -  Patient or family member is willing and able to perform clean intermittent
             catheterization for duration of this study

        Exclusion Criteria:

          -  Patient has received anticholinergic medication for the treatment of overactive
             bladder before randomization into the study

          -  Patient has history or evidence of any pelvic or urological abnormalities, bladder or
             urethral surgery or disease, other than neurogenic bladder related to spinal cord
             injury, that may impact bladder function

          -  Patient has significant stress urinary incontinence, determined by patient history, in
             the opinion of the investigator

          -  Neurogenic detrusor overactivity (greater than 10cm elevation in pdet pressure) at
             baseline urodynamic screening (Day 0)

          -  Patient found to have significant baseline renal pathology (e.g. hydronephrosis,
             stones, renal mass) at Day -7

          -  Patient has a history of two or more treated urinary tract infections within 6 months
             of screening Day -7

          -  Patient has urinary tract infection defined as a bacteriuria count of greater than
             105/ml conjoint with leukocyturia greater than 5hpf at screening Day -7

          -  Patient has asymptomatic urinary tract infection, defined as positive nitrites,
             leukocyte esterase and or blood on urine dipstick reagent strip at randomization Day 0

          -  Patient has history of unexplained hematuria or unexplained hematuria if greater than
             5 RBC's/hpf are present at screening Day -7

          -  Patient has active genital infection, other than genital warts, either concurrently or
             within 4 weeks prior to screening Day -7

          -  Patient has history of interstitial cystitis, in the opinion of the investigator

          -  Patient has evidence of urethral obstruction, in the opinion of the investigator at
             screening Day -7 or randomization Day 0

          -  Patient uses medications with anti-platelet or anti-coagulant effects (except Lovenox)
             within 10 days of randomization Day 0. Lovenox 30mg SQ every 12 hours is standard of
             care after SCI until 2-3 months post injury. Lovenox will be stopped 24 hours before
             and for 48 hours after each sphincter injection or bladder biopsy procedure.

          -  Patient has hemophilia, or other clotting factor deficiencies or disorders that cause
             bleeding diathesis

          -  Patient has previously been treated with any endovesical pharmacologic agent (e.g.
             capsaicin, resiniferatoxin)

          -  Patient has had previous or current botulinum toxin therapy of any serotype for any
             condition

          -  Patient has a known allergy or sensitivity to any components of the study medication,
             anesthetics or antibiotics to be used during the study

          -  Any medical condition that may put the patient at increased risk with exposure to
             Botox® including diagnosed myasthenia gravis, Eaton-Lambert syndrome or amyotrophic
             lateral sclerosis

          -  Females who are pregnant, nursing or planning a pregnancy during the study or females
             of child-bearing potential who are unable or unwilling to use a reliable form of
             contraception during the study

          -  Current or previous participation in another therapeutic study within 30 days of
             screening Day -7

          -  Any condition or situation which, in the investigator's opinion, puts the patient at
             significant risk, could confound the study results, or may interfere significantly
             with the patient's participation in the study