A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis. Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis. The efficacy of intravesical bacillus Calmette-Guerin in the treatment of interstitial cystitis: long-term followup. Intravesical bacillus Calmette-Guerin and dimethyl sulfoxide for treatment of classic and nonulcer interstitial cystitis: a prospective, randomized double-blind study. Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study. The amelioration of the suffering associated with spinal cord injury with subperception transcranial electrical stimulation. A meta-analysis comparing trials of antimuscarinic medications funded by industry or not. [Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test].
We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC).
                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 randomized 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, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively.
                A total of 265 participants were randomized 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.
                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. 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.
                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.
                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.
                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. To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC).
                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.
                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.
                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. Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, 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.
                Subjects randomized to receive BCG were followed at routine intervals with questionnaires 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.
                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 Rand-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.
                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. We conducted a prospective, 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.
                A total of 21 patients, including 11 with classic and 10 with nonulcer interstitial cystitis, randomly 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 questionnaires, including a visual analog pain scale and voiding diaries.
                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.
                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 resulted in a significant reduction in pain and urinary frequency, although only in patients with classic interstitial cystitis. We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy.
                A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl. Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment.
                In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup. There were no local side effects with either treatment. Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup.
                In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin. Double blind, partial crossover.
                To evaluate the analgesic activity of a novel cranial electrostimulus in people with spinal cord injury (SCI).
                Hereward College, a residential centre that provides educational facilities for students with disabilities.
                Subjects with SCI experiencing chronic pain were randomly assigned into two groups, one of which received sham and the other transcranial electrostimulation treatment (TCET) on two occasions daily for four successive days. After a 'wash-out' period of 8 weeks all subjects returned and received the identical stimulus that the treated cohort received on the first arm of the study.
                Pain measurements applied before and after each session indicated that the pain decreased in the treated group to 51% of that reported at the commencement of treatment; reported pain intensity did not decrease significantly in the sham treated subjects. The same (sham) subject group reported experiencing 59% of the pain at the end of the second arm of the study (TCET) as on the first arm (sham). No significant differences were determined between the mood of all subjects estimated before and after each sham or TCET treatment session. The reported analgesic, and combined antidepressant and anxiolytic drug use in subjects receiving TCET on the second arm of the study, was 46% and 53% respectively of the average pre-study drug use. No similar decrease in the use of the drugs was noted in the same subjects after sham treatment on the first arm of the study. Salivary cortisol determinations made prior to and after each sham and treatment session implicated this corticoid in the pain-relieving mode of action of the treatment, but could not be associated with any changes in mood. Subjects receiving TCET had significantly higher urinary 3-methoxy-4-hydroxy-phenylglycol (MHPG) output after the TCET treatment period than sham stimulation, implicating increased central noradrenaline (NA) metabolism in the observed effects.
                The subjects reported less pain during, and immediately after receiving this transcranial treatment, although they were using less medication than when receiving sham treatment. To determine if there is a significant difference in outcomes of clinical trials funded by industry or not of antimuscarinic medications used to treat overactive bladder (OAB) symptoms and detrusor overactivity (DOA).
                A Medline search was conducted from January 1966 to June 2003 to identify human clinical trials of oxybutynin and tolterodine published in English. Randomized controlled trials on subjects aged > or = 16 years who were being treated with oxybutynin or tolterodine for OAB symptoms or DOA; 24 studies were identified. The endpoints assessed were OAB symptoms or changes in uninhibited detrusor contractions on cystometrography. The outcome variables were dichotomized as 'improvement' or 'no improvement'. Odds ratios and 95% confidence intervals were calculated for each study based on data derived or extracted from tables and figures.
                Meta-analysis showed no significant difference in the outcomes trails funded by industry or not. Trials were then reviewed to determine their adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized trials.
                Clinical trials are important for clinicians when selecting medical therapies. In this analysis we found no difference in outcomes when comparing studies funded by industry or not for tolterodine and oxybutynin. The quality of all trials would be improved by close adherence to the CONSORT guidelines for randomized clinical trials. Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy.
Overall, the evidence base for treating PBS/IC using intravesical preparations is limited and the potential for meta-analysis reduced by variation in the outcome measures used. The quality of trial reports was mixed and in some cases this precluded any meaningful data extraction. 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. Randomised controlled trials are still needed and study design should incorporate outcomes that are most relevant to these with PBS/IC and should be standardised.