Several intravesical instillation regimens for the treatment of IC/BPS have been described in the literature, and they have been utilized for decades based on individual physician preference and anecdotal experience. To date, there has been a lack of evidence to inform best practices and to delineate the impact of the most commonly used intravesical IC/BPS therapies on both objective and subjective outcomes. The aim of this prospective RCT was to compare the overall impact of DMSO versus BTH intravesical installation therapy in female subjects newly diagnosed with IC/BPS.

The primary study outcome was defined as greater than 29.5% change in O’Leary-Sant Interstitial Cystitis Symptoms Index (ICSI) total score. Secondary outcomes included changes in urinary frequency and nocturia, and objective change in bladder capacity after treatment. We utilized change in bladder capacity as an objective outcome because reduced bladder capacity tends to be observed among patients with IC/BPS, and therefore may be expected to increase with successful treatment. Our hypothesis was that intravesical therapy with DMSO would be associated with a greater decrease in ICSI score, as well as a greater increase in bladder capacity as compared to intravesical BTH therapy for the treatment of IC/BPS.

This was a prospective, randomized, non-blinded study; a blinded study was not feasible due to the characteristic strong odor of DMSO. After obtaining IRB approval, patients with newly diagnosed IC/BPS were randomized 1:1, with treatment allocations stored in sealed opaque envelopes, to receive treatment with six weekly bladder instillations using either 50 mL DMSO and 1mL triamcinolone (10mg/mL) or 30 mL 0.5% bupivacaine (5mg/mL), 2 mL triamcinolone (10mg/mL), and 2 mL Heparin (10,000 units/mL). At each visit, subjects completed the O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI) and questionnaires detailing number of voids during day and night. Bladder capacity was measured at each visit by retrograde filling of the bladder with sterile water through a catheter, until the patient reported their maximum capacity sensation.

The ICSI is a valid and reliable method for measuring successful IC/BPS treatment, with a reduction of at least 29.5% in ICSI score corresponding with moderate to marked improvement in symptoms on the Patient Overall Rating of Improvement of Symptoms Index [1]. One study utilizing global assessments of response determined that 40% of patients receiving DMSO had a moderate improvement after treatment [2]. Another study determined that 15% of patients had a moderate response to lidocaine and heparin instillations [3]. Our power and sample size calculations were performed using these previously published response rates and using the validated outcome of a percent reduction in ICSI of at least 29.5%. It was determined that 49 subjects per group would be required to detect the expected difference in response (25%) with 80% power at a 0.05 significance level. Data were analyzed using Student’s t-test or Chi-squared tests.

Eighty-three patients were randomized and 70 participants completed the six once-weekly instillations (42 DMSO, 28 BTH). The groups were similar in baseline demographics and clinical characteristics with the exception of baseline CMG maximum capacity (DMSO 338.62 +/- 139.44mL, BTH 447.43+/- 180.38mL, p= 0.01). A greater than 29.5% reduction in total ICSI score was seen at the conclusion of treatment in 63% of DMSO patients and 43% of BTH patients (p=0.15). Overall, there was a significant difference in the change of total ICSI score favoring DMSO at visit 5 and 6 (p=0.02 each). At treatment visits 5 and 6, there were significantly greater improvements in the individual ICSI pain question for DMSO compared to BTH (p=0.03 and p=0.01, respectively). Significant improvements were observed in individual ICSI question scores between visits 1, 5 and 6 in regard to urgency, frequency, nocturia, and pain (p<0.0001 each) in the DMSO group, while questions addressing urgency and daytime frequency were significantly improved in the BTH treatment group (p=0.009 and p=0.003) but not for pain. 

Bladder capacity increased significantly from baseline for both DMSO and BTH (p<0.01 each). There was a nonsignificant difference in percent change in bladder capacity at the conclusion of treatment (DMSO 74% vs BHT 42%, p=0.16). There was no significant difference between treatment groups with respect to daytime voiding frequency or nocturia; however, there was a significant reduction in nocturia in the DMSO treatment arm (mean -1, p=0.01).

These data revealed several interesting and clinically relevant differences in outcomes between DMSO and BTH treatment groups, which became apparent only towards the end of the 6-week treatment cycle. Patients receiving their last two bladder instillations (weeks #5 and #6) of DMSO reported statistically significant improved pain as compared to those receiving BTH, according to individual ICSI question scores. Responses to ICSI questions pertaining to urgency, frequency, nocturia and bladder pain all improved significantly in the DMSO group, while questions addressing urgency and daytime frequency were significantly improved in the BTH treatment group. 

Bladder capacity increased from baseline in both groups, indicating that bladder instillations with DMSO and BTH are effective in improving capacity. The maximum capacity was significantly lower in the DMSO group, at baseline. While a statistically significant difference between percent change in bladder capacity was not observed between the two groups, a trend suggested the possibility of a greater increase in bladder capacity from baseline in the DMSO versus the BTH group; further exploring this finding may require a larger sample size.

Whereas the percentage of patients reporting greater than 29.5% reduction in total ICSI score was not statistically significant between the two treatment groups (63% of DMSO and 43% of BTH, p=0.15), this finding may have been impacted by our recruitment not achieving the target of 49 per group as defined by the power calculation. Despite this limitation, the individual ICSI question analyses, as well as bladder capacity analysis, all revealed positive findings pointing towards consistent conclusions relating to our fundamental study questions: both therapies demonstrate the ability to provide effective symptom relief and improved bladder capacity, and when systematically compared in newly diagnosed IC/BPS patients, DMSO appears to outperform BTH in several respects. As always, these findings need to be considered through additional perspectives including cost, which were not addressed by the current study.

Bladder instillations with DMSO or BTH provide overall symptomatic improvement, larger bladder capacity, and improved frequency and nocturia in patients with newly diagnosed IC/BPS. DMSO appears to provide greater improvement in symptoms, particularly bladder pain. The impact of these therapies, and the differences between groups, tend to be fully revealed only after 5 sessions of once-weekly therapy.

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