Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial.
OBJECTIVE
Interstitial cystitis is a painful bladder condition of unknown etiology and poorly understood pathophysiology. Current therapies have met with limited success. Vanilloid receptor agonists such as resiniferatoxin (RTX) desensitize C-fibers that transmit pain; it is hypothesized that such drugs will be effective in the treatment of interstitial cystitis and painful bladder syndrome by decreasing the pain that leads to urinary frequency and urgency.


METHODS
A randomized, double-blind, placebo controlled study was conducted in 163 patients with interstitial cystitis. Participants were randomly assigned to receive a single intravesical dose of 50 ml of either RTX 0.01 microM, 0.05 microM, 0.10 microM, or placebo. Safety and efficacy was evaluated over 12 weeks. The primary efficacy endpoint was the Global Response Assessment, a 7-point scale rating overall change in symptoms of interstitial cystitis after 4 weeks. Secondary efficacy endpoints included reduction in pain, urgency, frequency, nocturia, average void volume, and the O'Leary-Sant Symptom and Problem Indexes.


RESULTS
RTX did not improve overall symptoms, pain, urgency, frequency, nocturia, or average void volume during 12 weeks followup. RTX resulted in a dose-dependent increase in the incidence of instillation pain, but was otherwise generally well tolerated.


CONCLUSIONS
In the largest prospective, randomized clinical trial reported to date with intravesical vanilloid therapy, single administration of RTX at doses of 0.01 microM to 0.10 microM was not effective in patients with interstitial cystitis.
Payne
Christopher K
CK
Stanford University School of Medicine, Stanford, California, USA. cpayne@stanford.edu
Mosbaugh
Philip G
PG
Forrest
John B
JB
Evans
Robert J
RJ
Whitmore
Kristene E
KE
Antoci
Joseph P
JP
Perez-Marrero
Ramon
R
Jacoby
Karny
K
Diokno
Ananias C
AC
O'Reilly
Keith J
KJ
Griebling
Tomas L
TL
Vasavada
Sandip P
SP
Yu
Albert S
AS
Frumkin
Lyn R
LR
D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D018856:Cystitis, Interstitial / Q000188:drug therapy*; D004224:Diterpenes / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009498:Neurotoxins / Q000008:administration & dosage*
D004224:Diterpenes; D009498:Neurotoxins; C024353:resiniferatoxin