title: Etiology, pathogenesis, and diagnosis of interstitial cystitis. The efficacy of intravesical bacillus Calmette-Guerin in the treatment of interstitial cystitis: long-term followup. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis. Research criteria versus clinical criteria for interstitial cystitis. Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study. A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis. Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC) A prospective, double‐blind, randomized cross‐over study evaluating changes in urinary pH for relieving the symptoms of interstitial cystitis The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial. Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. Intravesical bacillus Calmette-Guerin and dimethyl sulfoxide for treatment of classic and nonulcer interstitial cystitis: a prospective, randomized double-blind study. Intravesical capsaicin for treatment of severe bladder pain: a randomized placebo controlled study. Interstitial cystitis: bladder training with intravesical oxybutynin. Psychometric analysis of the University of Wisconsin Interstitial Cystitis Scale: implications for use in randomized clinical trials. A controlled study of dimethyl sulfoxide in interstitial cystitis.
abstract: Interstitial cystitis ( IC ) is a bladder syndrome of unknown etiology . The cause of IC is most likely multifactorial and includes genetic and environmental factors . Various pathophysiological changes in the bladder , pelvis , and peripheral and central nervous systems have been identified , and this has led to the emergence of biologically specific treatment modalities . Interstitial cystitis is being diagnosed with increasing frequency ; however , current diagnostic criteria are non-uniform , and there is significant overlap between chronic pelvic pain syndromes in men and women , interstitial cystitis , recurrent " cystitis , " and the overactive bladder syndrome . The diagnosis of interstitial cystitis can be made clinical ly and by cystoscopy and hydrodistension . The sensitivity and specificity of urinary markers and the potassium sensitivity test have not been prospect ively studied PURPOSE Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency . A prospect i ve , double-blind , placebo controlled study of the use of intravesical bacillus Calmette-Guerin ( BCG ) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months . Results demonstrated a 60 % BCG response rate , compared to a 27 % placebo response rate . We now report the long-term followup results of those patients who received intravesical BCG .  MATERIAL S AND METHODS Subjects r and omized to receive BCG  were followed at routine intervals with question naires and voiding diaries identical to those in the blinded study . Adverse events were closely monitored in the treatment and followup phases of the study . Subject baseline values were compared to followup data . RESULTS Of the BCG responders mean followup was 27 months ( range 24 to 33 ) , and 8 of 9 ( 89 % ) continue to have an excellent response in all parameters measured . The global interstitial cystitis survey improved 70 % , daily voids decreased 31 % , nocturia improved 54 % , mean voided volume increased 61 % , pelvic pain decreased 81 % , vaginal pain decreased 71 % , urgency decreased 71 % and dysuria decreased 82 % . Overall well-being improved 54 % and the R and -36 quality of life survey overall improved 64 % . In 86 % of the patients ( 6 of 7 ) dyspareunia resolved . Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup , suggesting that BCG does not worsen interstitial cystitis symptoms . No long-term adverse events from BCG were noted . CONCLUSIONS Intravesical Tice BCG is safe , effective and durable in the treatment of interstitial cystitis . Of those patients who received only 6 weekly treatments and responded favorably 89 % continue to have an excellent response with followup ranging from 24 to 33 months OBJECTIVE To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate ( PPS ) compared with placebo in patients with interstitial cystitis ( IC ) . PATIENTS AND METHODS Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study ; 10 received intravesical PPS ( 300 mg in 50 mL of 0.9 % sodium chloride ) applied twice a week for 3 months and the other 10 received a placebo .  Symptomatic relief and objective variables ( bladder capacity voiding volumes and urinary frequency ) were assessed after 3 months and the long-term outcome of those continuing treatment was determined . RESULTS Of the patients treated with PPS , four gained significant symptomatic relief compared with only two receiving placebo . Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS ( P = 0.047 ) . At 18 months from the start of the study , the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment . CONCLUSIONS These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects In March 2003 experts on interstitial cystitis ( IC ) from around the world met in Kyoto , Japan for a series of workshops intended to define areas of agreement and difference in the approach to this disease . This workshop explored the diagnostic criteria IC in the clinical and research setting s. The NIDDK criteria are used almost universally for research but there is tremendous disparity in the clinics and no consensus at all as to the best practice in diagnosing IC for clinical purpose s. Throughout the world many physicians use the NIDDK research criteria for clinical diagnosis ; in some countries this is st and ard . Undoubtedly , this m and ates under-diagnosis and denies treatment to many patients . Still , a majority feel that one diagnostic system is m and atory to promote clarity in communication . The group called for two initiatives to help advance this area of controversy : ( 1 ) a large-scale , prospect i ve study critically examining the role of  cystoscopy , bladder distention , and biopsy  in the diagnosis of IC ; ( 2 ) a concerted effort to develop a single evidence -based guideline or algorithm that would be flexible enough to meet the needs of clinicians , research ers , and patients PURPOSE Present therapeutic approaches to control hypersensitive disorder of the lower urinary tract and bladder pain are clinical ly and scientifically unsatisfactory . We performed a r and omized placebo controlled study with followup after 1 and 3 months using intravesical resiniferatoxin to treat hypersensitive disorder and bladder pain . MATERIAL S AND METHODS We prospect ively r and omized 18 patients into 2 groups to receive a single dose of 10 nM. resiniferatoxin intravesically ( group 1 ) or a placebo saline solution only ( group 2 ) . All patients had at least a 6-month history of frequency , nocturia , urgency and symptoms of pelvic pain as well as no urinary tract infection within the last 3 months , functional disorders of the lower urinary tract , or other vesical or urethral pathology . Pretreatment voiding pattern and pain score were recorded . Patients were evaluated after 30 days ( primary end point ) and 3 months ( secondary end point ) . RESULTS The 2 groups were adequately homogeneous in regard to patient age , sex ratio , disease duration , voiding pattern and pain score . At the primary end point mean frequency plus or minus st and ard error of mean was decreased from 12 . 444 + /- 0.70 voids to 7.111 + /- 0.67 and nocturia from 3.777 + /- 0 . 27 to 1.666 + /- 0.16 ( p < 0.01 ) . We observed a lesser significant improvement in mean frequency in group 1 at the secondary end point to 10.444 + /- 0.94 voids ( p < 0.05 ) . No significant modification was noted in patients assigned to placebo .  Mean pain score significantly decreased in group 1 at the primary end point from 5.555 + /- 0.29 to 2.666 + /- 0.23 ( p < 0.01 ) but not at the secondary end point ( 4.777 + /- 0.66 , p > 0.05 ) . No statistically significant improvement in mean pain score was observed in placebo group 2 . During resiniferatoxin infusion 4 group 1 patients noticed a light warm or burning sensation at the suprapubic and /or urethral level . CONCLUSIONS Intravesical resiniferatoxin may significantly improve the voiding pattern and pain score in patients with hypersensitive disorder and bladder pain . Because resiniferatoxin did not cause a significant warm or burning sensation at the suprapubic and /or urethral level , it may be considered a new strategy for treating hypersensitive disorder and bladder pain . However , further studies are necessary to confirm our results and define the resiniferatoxin mechanism of action , dose and necessary treatment schedule PURPOSE We compared intravesical bacillus Calmette-Guerin ( BCG ) to placebo instillations in patients with treatment refractory interstitial cystitis ( IC ) . MATERIAL S AND METHODS Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC , and reported at least moderate pain and frequency for a minimum of 6 months before study entry , were r and omized to 6 weekly double-blinded intravesical instillations of either BCG or placebo , and then followed for a total of 34 weeks . The primary outcome was a patient reported global response assessment at week 34 , supplemented with medications for IC during weeks 31 to 34 . Secondary outcomes included a 24-hour voiding diary , pain , urgency , vali date d IC symptom indexes and adverse events . The target sample size was 260 participants , design ed to detect a difference in response rates between placebo and BCG of 30 % and 50 % , respectively . RESULTS A total of 265 participants were r and omized and 17 ( 6 % ) patients withdrew from study . The response rates for the primary outcome were 12 % for placebo and 21 % for BCG ( p = 0.062 ) . Small improvements were observed for all secondary outcomes , some more so with BCG , but these differences were of borderline statistical significance . Although a large number of adverse events were reported in the BCG arm , there was no statistically significant difference between the treatment arms in overall adverse event rates . CONCLUSIONS Although the BCG safety profile was acceptable , the response rate for the primary outcome was low . Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive Objective : To determine the safety and tolerability of intravesical resiniferatoxin ( RTX ) in interstitial cystitis ( IC ) patients . Material s and Methods : IC patients were instilled with 50 cc of test solution containing either placebo , 0.05 μM or 0.10 μM RTX in the bladder . Plasma concentration of RTX and its degradant resiniferonol 9- , 13- , 14-orthophenylacetate was measured . Immediate post-treatment blood sampling and cystoscopy were performed . Symptoms were evaluated before treatment , at 4- and at 12-week follow-ups , using VAS indicator for pain , voiding diary , and O’Leary ’s IC symptom/problem indices . Results : Among 22 patients observed ( ten in 0.10 μM RTX , eight in 0.05 μM RTX , and four in placebo groups ) , the most commonly reported adverse event was pain during instillation ( 80.0 % , 87.5 % , and 25.0 % ) . No serious adverse events were reported . Conclusions : Use of intravesical RTX in IC patients is associated with important tolerability issues but safe at 0.10 μM and 0.05 To provide evidence for the clinical efficacy of changes in urinary pH on the pain associated with interstitial cystitis ( IC ) PURPOSE Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure . A recent report suggested that bacillus Calmette-Guerin ( BCG ) may be effective in the treatment of interstitial cystitis . A r and omized , prospect i ve , double-blind , placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done . MATERIAL S AND METHODS Patients meeting the National Institute of Arthritis , Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo .  Periodic question naires , voiding diaries and cystometrograms were obtained . A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months ( range 6 to 13 ) . Based on an exit question naire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better . RESULTS A 60 % BCG response rate was noted , compared to a 27 % placebo response rate . Minimum voided volume and quality of life improved in the BCG group compared to placebo .  Adverse events were similar in each group , mostly irritative in nature , and no significant systemic events were noted . CONCLUSIONS Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis . Additional studies must be performed to confirm the results of this pilot study PURPOSE 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 . MATERIAL S AND METHODS A r and omized , double-blind , placebo controlled study was conducted in 163 patients with interstitial cystitis . Participants were r and omly 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 result ed in a dose-dependent increase in the incidence of instillation pain , but was otherwise generally well tolerated . CONCLUSIONS In the largest prospect i ve , r and omized 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 PURPOSE We conducted a prospect i ve , double-blind study with a crossover design of intravesical bacillus Calmette-Guerin ( BCG ) and dimethyl sulfoxide to determine whether patients with classic and nonulcer interstitial cystitis , respectively , might benefit from either regimen . MATERIAL S AND METHODS A total of 21 patients , including 11 with classic and 10 with nonulcer interstitial cystitis , r and omly underwent treatments with intravesical BCG or dimethyl sulfoxide and , if not improved , were treated with the other substance after a washout period . All 21 patients were evaluated with symptom question naires , including a visual analog pain scale and voiding diaries . RESULTS Regardless of regimen , there was no improvement in maximal functional capacity . There was a reduction in urinary frequency following dimethyl sulfoxide treatment but only in the classic subtype ( p < 0.05 ) , whereas no reduction was seen following BCG in either subtype . A substantial pain decrease was noted in classic ( p < 0.05 ) as well as nonulcer ( p < 0.05 ) interstitial cystitis following dimethyl sulfoxide . CONCLUSIONS Intravesical BCG has been presented as a promising new option for treatment of interstitial cystitis . We failed to demonstrate benefit from this treatment . Dimethyl sulfoxide had no positive effect on maximal functional capacity but result ed in a significant reduction in pain and urinary frequency , although only in patients with classic interstitial cystitis PURPOSE Present therapeutic approaches to control bladder pain are clinical ly and scientifically unsatisfactory , and pain in the lower urinary tract remains a challenge even to the skilled urologist . A r and omized placebo controlled study was done to evaluate intravesical capsaicin for severe bladder pain . Followup was 6 months . MATERIAL S AND METHODS A total of 36 patients was prospect ively r and omized into those receiving 10 microM. intravesical capsaicin twice weekly for 1 month ( group 1 ) or placebo ( group 2 ) . All patients had pelvic pain for at least 6 months , and had no urinary tract infection within the last 3 months , functional disorders of the lower urinary tract , or other vesical or urethral pathology . Pretreatment voiding pattern and pain score were recorded . Patients were evaluated immediately at the end of treatment ( primary end point ) and 6 months later ( secondary end point ) . RESULTS Both groups were adequately homogeneous with regard to age , sex ratio , duration of disease , voiding pattern and pain score . At both end points group 1 had significant improvement in frequency and nocturia but no improvement in urgency . No change was noted in group 2 . A significant decrease in pain score was found in group 1 at the primary ( mean plus or minus st and ard deviation 3.22 + /- 0.42 , p < 0.01 ) and secondary ( 3.83 + /- 0.47 , p < 0.01 ) end points compared to before treatment ( 5.61 + /- 0.40 , chi-square with 2 degrees of freedom 29.25 , p < 0.0001 ) . A significant improvement was also observed in the placebo group , in which the pretreatment pain score ( 5.47 + /- 0.37 ) was decreased at the primary ( 4.47 + /- 0.36 , p < 0.01 ) and secondary ( 4.48 + /- 0.34 , p < 0.01 , chi-square with 2 degrees of freedom 12.71 , p < 0.002 ) end points . There were no statistically significant differences between the 2 groups . CONCLUSIONS We confirmed the beneficial effect of intravesical instillation of capsaicin on voiding pattern in patients with hypersensitive disorders ( frequency and nocturia ) . We could not confirm improvement in pain score after capsaicin treatment compared to placebo . Possibly a larger dose of capsaicin would be more effective in controlling pain and neurological disease of the bladder PURPOSE We assess the efficacy of intravesical administration of oxybutynin chloride in patients with interstitial cystitis . MATERIAL S AND METHODS The study included 36 women with a mean age of 45 years with a diagnosis of interstitial cystitis . Patients were treated with gradual intravesical instillation of saline oxybutynin solution ( oxybutynin group ) or gradual filling of simple saline ( control group ) . Evaluation parameters consisted of symptom problem index , voids per day , volume per void , functional bladder capacity , volume at first sensation , cystometric bladder capacity and cystometric volume at first sensation . RESULTS Statistically significant improvement of all evaluated parameters was found in both groups . When comparing the outcomes statistically significant improvement of parameters favored the oxybutynin group . CONCLUSIONS Bladder training alone produces a satisfactory result by gradually exp and ing the bladder , and an additional statistically significant improvement is evident with intravesical oxybutynin PURPOSE A psychometric analysis of the University of Wisconsin Interstitial Cystitis Scale was conducted on 30 females previously enrolled in a phase II double-blind r and omized controlled trial evaluating the efficacy of six weekly intravesical instillations of TICE BCG .  The analyses were to : ( 1 ) evaluate the adequacy of the seven individual IC component items for measuring the range of patient responses ; ( 2 ) verify the 2-factor ( IC versus reference ) construct of the scale ; ( 3 ) evaluate the internal consistency and reliability of the IC items ; ( 4 ) better define the scale 's applicability and limitations ; and ( 5 ) if possible , make recommendations for improvements in the scale . MATERIAL S AND METHODS St and ard psychometric analyses were used to perform the evaluation , and included descriptive analysis of individual items , computing of item-total correlations and Cronbach 's internal consistency measures , and the application of factor and Rasch analyses . RESULTS The original 7-item IC scale was found to have ceiling effects that could limit its use in detecting small therapeutic differences . It was also found that the Pelvic item originally assigned to the reference set of items of the scale should be included as an IC item when used in a comparable IC population . After including this item into the IC scale Cronbach 's alpha was 0.84 , compared with 0.82 . CONCLUSIONS The UW-IC Scale has psychometric properties similar to other measurement instruments used in clinical research , and appears worthy of further study in well-characterized IC population s. The reference items suggest that IC patients do not indiscriminately report high values for generalized body complaints , but do so on bladder related symptoms as recorded by the IC items of the scale . Although the scale has limitations it appears applicable for use in future IC intervention clinical trials To evaluate the effectiveness of dimethyl sulfoxide in the treatment of patients with biopsies suggestive of interstitial cystitis , 33 patients underwent a controlled crossover trial . Patients were allocated r and omly to receive 50 per cent dimethyl sulfoxide or placebo ( saline ) . The medication was administered intravesically every 2 weeks for 2 sessions of 4 treatments each . Response was assessed urodynamically and symptomatically . Thirty women and 3 men ( mean age 48 years and mean duration of symptoms 5.5 years ) were entered into the study . No significant side effects to dimethyl sulfoxide were noted . When assessed subjectively , 53 per cent of dimethyl sulfoxide treated patients were markedly improved compared to 18 per cent of the placebo treated patients . Of the dimethyl sulfoxide group 93 per cent had objective improvement versus 35 per cent of the placebo group . Thus , dimethyl sulfoxide proved to be superior to placebo in the objective and subjective improvement of patients with interstitial cystitis
target: Resiniferatoxin was not associated with sustained differences in the review outcomes reported but pain during instillation and withdrawal from treatment was significantly more common .
  Groups treated with BCG tended to report less pain and fewer general symptoms .
  Although adverse events were commonly reported , these were no more common after BCG than after placebo instillation .
  The few data about Pentosanpolysulphate tended to favour the actively treated , but with wide confidence intervals ; there was little information about adverse events .
  Oxybutinin instillation was associated with increased bladder capacity , reduced frequency , improved quality of life scores and fewer drop-outs .
  Alkalinisation of urine pH did not make any clear difference , but with potentially wide confidence intervals .
  BCG and oxybutin are reasonably well-tolerated and evidence is most promising for these .
  Resiniferatoxin showed no evidence of effect for most outcomes and caused pain , which reduced treatment compliance .
  There is little evidence for the other treatments included in this review .
background: BACKGROUND Painful Bladder Syndrome/Interstitial Cystitis ( PBS/IC ) occurs predominantly in women .
  It is a poorly-understood condition with symptoms of bladder pain , urinary frequency , urgency and nocturia .
  Treatments for PBS/IC include dietary/lifestyle interventions , oral medication , intravesical instillations and , in some cases , surgery .
  Success rates are generally modest and there is little consensus as to the best form of treatment for this condition .
  OBJECTIVES To assess the effectiveness of intravesical treatment for PBS/IC .