Intravesical resiniferatoxin for refractory detrusor hyperreflexia: a multicenter, blinded, randomized, placebo-controlled trial

J Spinal Cord Med. 2003 Winter;26(4):358-63. doi: 10.1080/10790268.2003.11753706.

Abstract

Objective: Resiniferatoxin (RTX) is an analogue of capsaicin with more than 1,000 times its potency in desensitizing C-fiber bladder afferent neurons. This study investigated the safety and efficacy of intravesical RTX in patients with refractory detrusor hyperreflexia (DH).

Methods: Thirty-six (22 males, 14 females) neurologically impaired patients (20 spinal cord injury, 7 multiple sclerosis, 9 other neurologic diseases) with urodynamically verified DH and intractable urinary symptoms despite previous anticholinergic drug use were treated prospectively with intravesical RTX using dose escalation in a double-blind fashion at 4 centers. Patients received a single instillation of 100 mL of placebo (n = 8 patients) or 0.005, 0.025, 0.05, 0.10, 0.2, 0.5, or 1.0 microM of RTX (n = 4 each group). A visual analog pain scale (VAPS) (0-10; 10 = highest level of pain) was used to quantify discomfort of application. Treatment effect was monitored using a bladder diary and cystometric bladder capacity at weeks 1, 3, 6, and 12 posttreatment.

Results: Mean VAPS scores revealed minimal to mild discomfort with values of 2.85 and 2.28 for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. Due to the small sample size, there were no statistically significant changes in mean cystometric capacity (MCC) or incontinence episodes in each treatment dose group. However, at 3 weeks, MCC increased by 53% and 48% for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. Patients in the 0.5-microM and 1.0-microM groups with MCC < 300 mL at baseline showed greater improvements in MCC at 120.5% and 48%, respectively. In some patients, MCC increased up to 500% over baseline, despite a low RTX dose. Incontinence episodes decreased by 51.9% and 52.7% for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. There were no long-term complications.

Conclusion: Intravesical RTX administration, in general, is a well-tolerated new therapy for DH. This patient group was refractory to all previous oral pharmacologic therapy, yet some patients responded with significant improvement in bladder capacity and continence function shortly after RTX administration. Patients at risk for autonomic dysreflexia require careful monitoring during RTX therapy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Intravesical
  • Adult
  • Aged
  • Diterpenes / administration & dosage*
  • Diterpenes / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / complications*
  • Muscle Hypertonia / drug therapy*
  • Muscle Hypertonia / etiology
  • Nerve Fibers, Unmyelinated / drug effects
  • Nervous System Diseases / complications*
  • Neurotoxins / administration & dosage*
  • Neurotoxins / adverse effects
  • Pain Measurement
  • Risk Factors
  • Spinal Cord Injuries / complications*
  • Treatment Outcome
  • Urinary Bladder / innervation
  • Urinary Bladder, Neurogenic / drug therapy*
  • Urinary Bladder, Neurogenic / etiology
  • Urodynamics / drug effects

Substances

  • Diterpenes
  • Neurotoxins
  • resiniferatoxin