Comparison of the Treatment of Refractory Bladder Pain Syndrome With DMSO and DMSO With Botulinum Toxin A
Condition: Bladder Pain Syndrome
MeSH terms: Cystitis, Interstitial; Syndrome; Somatoform Disorders
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The purpose of this research study is to evaluate the efficacy of intravesical botulinum A
      toxin and DMSO in women with bladder pain syndrome who have not responded to first-line
      treatments. Bladder pain syndrome is suprapubic pain with bladder filling as well as
      frequency, urgency, and nocturia in the absence of urinary tract infection or other
      pathology. DMSO has been shown to reduce pain in women with bladder pain syndrome as well as
      increase bladder absorption of various drugs. Botulinum toxin A has also been shown to
      improve pain in women with bladder pain syndrome when injected into the bladder suburothelium
      via a cystoscope. The main objective of this study is to assess if DMSO can deliver botulinum
      toxin to the suburothelium of the bladder to produce the same effect as direct injection of
      Botulinum toxin and a better effect than DMSO alone.
    

Detailed description: 
      Bladder pain syndrome (BPS) is defined by the AUA as an unpleasant sensation (pain, pressure,
      discomfort) perceived to be related to the urinary bladder, associated with lower urinary
      tract symptoms of more than six weeks duration, in the absence of infection or other
      identifiable causes. If the patient also has atypical cystoscopic and histological features
      then they are categorized as having Interstitial Cystitis.

      Dimethyl sulfoxide (DMSO) is an FDA-approved treatment for BPS and is thought to work by its
      exceptional solvent properties. It has been shown to desensitize nociceptive pathways in the
      lower urinary tract. It has been shown to improve pain in women with refractory BPS utilized
      initially in the 1960s when Stewart began instilling it intravesically.

      DMSO has also long been known to increase absorption of other agents instilled into the
      bladder. In a Japanese study, female rats were instilled with a chemotherapeutic agent as
      well as DMSO or just the chemotherapy alone. Using fluorescence they were able to show that
      with DMSO the chemotherapy drug was able to extend into the deeper layers of the bladder wall
      compared to just the epithelial layer in those that received just the chemotherapy drug.

      Botulinum toxin A is thought to work by decreasing acetylcholine release and causing
      paralysis of muscle tissue in smooth and striated muscle. It has been shown to improve pain
      in women with BPS when administered via injection It has also been shown to improve
      frequency/urgency in patients with BPS. Botulinum toxin has been shown to be effective when
      injected into the bladder urothelium for patients with overactive bladder.

      The investigators hypothesize that DMSO can deliver botulinum toxin to the suburothelium of
      the bladder to produce the same or similar effect as direct injection. Prior studies in women
      with refractory OAB showed that instillation resulted in improved continence, urgency, and
      quality of life as measured by UDI-6 and IIQ-7 questionnaires. In a prospective randomized
      study patients who received bladder instillation of liposome encapsulated botulinum toxin had
      improvement of their overactive bladder symptoms.

      The investigators hope to show this improvement in patients with bladder pain
      syndrome/interstitial cystitis. Botulinum toxin has a variable duration of effect in the
      bladder similar to other parts of the body. In one study, duration of improvement was
      estimated to be 7 to 12 months.
    

Intervention name(s): DMSO; Botox
Intervention type(s): Drug; Drug
Intervention description(s): DMSO will be instilled intravesically.; Botox will be instilled intravesically with DMSO.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment