Direct instillation of a solution containing botulinum toxin Type A (Botox) and dimethyl sulfoxide (DMSO [Rimso-50]) appears to be a safe and potentially promising method of treating women with voiding dysfunction associated with detrusor overactivity, according to results of a Phase I/II trial conducted by researchers at Mayo Clinic, Jacksonville, Fla.

This novel method of delivering botulinum toxin Type A to the bladder has obvious advantages over the current standard approach of injecting the agent into the detrusor muscle through a cystoscope-based procedure.

"Once the efficacy of botulinum toxin Type A for use in overactive bladder had been established, our team started looking for a way of delivering the agent that would not require a cystoscope or anesthetic," says first author Steven P. Petrou, MD, professor of urology at Mayo Clinic. "The idea for this less-invasive approach took its roots from collegial discourse and a review of the literature where DMSO was used as a carrier agent with other bladder-based medicines."

The 25 women enrolled in the Mayo trial had urodynamically confirmed detrusor overactivity and had failed at least two oral anticholenergic therapies. Petrou describes these women as suffering from severe incontinence and being at the end of the line in terms of oral medical treatment options.

The first nine patients enrolled constituted the Phase I portion of the study, with three women receiving a 66% dosing of the botulinum toxin Type A/DMSO bladder solution followed by six receiving the full dose. At 3-month follow-up, none of the patients had suffered any serious adverse events, nor had any experienced a clinically significant increase in postvoid residuals.

The remaining patients were given a full 300-unit dose of botulinum toxin Type A with 50 cc of DMSO (50% concentration) to complete the Phase II portion of the study.

Among the 21 women who received the full dosage and completed all follow-up visits (one withdrew for reasons unrelated to the study), there was a reduction in median 24-hour pad weight from baseline (135 grams) to 1 month (46 grams, p = .21) and 3 months (55 grams, p = .43).

Patients also reported improvements from baseline to 1 month in median scores on various quality of life and impact questionnaires, including the Incontinence Impact Questionnaire ([IIQ-7] 13 to 7, p = .007), Unified Dosimetry Index ([UDI] 10 to 6, p = .003), and Incontinence Quality of Life Questionnaire ([I-QOL] 45 to 79, p < .001). Similar improvements were reported at 3 months (all p ≤ .002).

Eleven women (52%) reported severe urgency at baseline, but only one (p < .001) and three (p = .004) still reported severe urgency at 1 and 3 months, respectively.

"We had hoped for demonstrable efficacy, and were pleased with the results, especially at the 1-month point," Petrou says.

If there is any reason for concern, it lies in the durability of the treatment. The median number of incontinence episodes dropped from four at baseline to two at 1 month (p = .004), but returned to four at 3 months (p = .81).

The study establishes the need of further research into this delivery method. For the Phase III study, in addition to enrolling women who will receive the two-drug instillation, Petrou and colleagues also will enroll a control group of similar women who will receive instillation of a solution of DMSO only. This will allow investigators to examine whether the benefit they observed in the Phase I/II trial stems from the botulinum toxin Type A itself or a placebo effect.

[Source: Urology Times]