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Comparison of the Treatment of Refractory Bladder Pain Syndrome With DMSO and DMSO With Botulinum Toxin A

Primary Purpose

Bladder Pain Syndrome

Status
Completed
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
DMSO
Botox
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Pain Syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Women ages 18-75 years, capable of giving consent
  2. Previously diagnosed with bladder pain syndrome/Interstitial cystitis that is refractory to dietary and behavioral modifications with an O'Leary-Sant score of 12 at baseline.
  3. Patients should have no change in their oral medications for bladder pain syndrome in the last 3 months
  4. Patients with respiratory conditions will be required to present a medical clearance before administration Botulinum toxin.

Exclusion Criteria:

  • 1. active treatment for bladder pain syndrome that is satisfactory to reduce symptoms 2. Urinary tract infection in the previous 6 weeks 3. History of bladder cancer, high grade dysplasia or radiation cystitis 4. Current or planned pregnancy in the next 6 months 5. Any change to regimen for lower urinary tract manipulations in the past 8 weeks (including Interstim, Tibial Nerve stimulation, pelvic floor muscle training, and biofeedback) 6. Previous botulinum toxin instilled or injected in the last 6 months. 7. Subjects cannot be homeless persons, or have active drug/alcohol dependence or abuse history 8. Subjects cannot have a personal history of a hypersensitivity reaction to Botulinum Toxin A

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    DMSO alone

    DMSO with Botox

    Arm Description

    Half of the patients will undergo DMSO instillation

    The other half will be randomized to DMSO mixed with 200U of botulinum toxin instillation

    Outcomes

    Primary Outcome Measures

    Pain Score
    We hypothesize that DMSO can deliver botulinum toxin to the suburothelium of the bladder to produce the same effect as direct injection of botulinum toxin via cystoscopy. The primary endpoint will be a pain score as measured by visual analog scale at 2 months post-instillation compared to pre-instillation pain score. We hypothesize that the effect of DMSO will have dissipated by that point and any improvement in pain will be attributable to the effects of botox.

    Secondary Outcome Measures

    Full Information

    First Posted
    March 31, 2017
    Last Updated
    June 8, 2017
    Sponsor
    University of Pennsylvania
    Collaborators
    Society for Urodynamics and Female Urology
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03103594
    Brief Title
    Comparison of the Treatment of Refractory Bladder Pain Syndrome With DMSO and DMSO With Botulinum Toxin A
    Official Title
    Comparison of the Treatment of Refractory Bladder Pain Syndrome With Dimethyl Sulfoxide (DMSO) Alone and DMSO as a Carrier Molecule for Botulinum Toxin A Instillation.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    August 2015 (Actual)
    Primary Completion Date
    August 2016 (Actual)
    Study Completion Date
    April 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Pennsylvania
    Collaborators
    Society for Urodynamics and Female Urology

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Bladder Pain Syndrome

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Masking Description
    The patients will not be notified of which arm they are randomized to.
    Allocation
    Randomized
    Enrollment
    2 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    DMSO alone
    Arm Type
    Active Comparator
    Arm Description
    Half of the patients will undergo DMSO instillation
    Arm Title
    DMSO with Botox
    Arm Type
    Experimental
    Arm Description
    The other half will be randomized to DMSO mixed with 200U of botulinum toxin instillation
    Intervention Type
    Drug
    Intervention Name(s)
    DMSO
    Intervention Description
    DMSO will be instilled intravesically.
    Intervention Type
    Drug
    Intervention Name(s)
    Botox
    Intervention Description
    Botox will be instilled intravesically with DMSO.
    Primary Outcome Measure Information:
    Title
    Pain Score
    Description
    We hypothesize that DMSO can deliver botulinum toxin to the suburothelium of the bladder to produce the same effect as direct injection of botulinum toxin via cystoscopy. The primary endpoint will be a pain score as measured by visual analog scale at 2 months post-instillation compared to pre-instillation pain score. We hypothesize that the effect of DMSO will have dissipated by that point and any improvement in pain will be attributable to the effects of botox.
    Time Frame
    6 months

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Women ages 18-75 years, capable of giving consent Previously diagnosed with bladder pain syndrome/Interstitial cystitis that is refractory to dietary and behavioral modifications with an O'Leary-Sant score of 12 at baseline. Patients should have no change in their oral medications for bladder pain syndrome in the last 3 months Patients with respiratory conditions will be required to present a medical clearance before administration Botulinum toxin. Exclusion Criteria: 1. active treatment for bladder pain syndrome that is satisfactory to reduce symptoms 2. Urinary tract infection in the previous 6 weeks 3. History of bladder cancer, high grade dysplasia or radiation cystitis 4. Current or planned pregnancy in the next 6 months 5. Any change to regimen for lower urinary tract manipulations in the past 8 weeks (including Interstim, Tibial Nerve stimulation, pelvic floor muscle training, and biofeedback) 6. Previous botulinum toxin instilled or injected in the last 6 months. 7. Subjects cannot be homeless persons, or have active drug/alcohol dependence or abuse history 8. Subjects cannot have a personal history of a hypersensitivity reaction to Botulinum Toxin A
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Ariana Smith, MD
    Organizational Affiliation
    University of Pennsylvania
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    No plan to share individual participant data.
    Citations:
    PubMed Identifier
    2719523
    Citation
    D'Ascanio P, Pompeiano M, Tononi G. Inhibition of vestibulospinal reflexes during the episodes of postural atonia induced by unilateral lesion of the locus coeruleus in the decerebrate cat. Arch Ital Biol. 1989 Mar;127(2):81-97.
    Results Reference
    background
    PubMed Identifier
    24676791
    Citation
    Cui Y, Zhou X, Zong H, Yan H, Zhang Y. The efficacy and safety of onabotulinumtoxinA in treating idiopathic OAB: A systematic review and meta-analysis. Neurourol Urodyn. 2015 Jun;34(5):413-9. doi: 10.1002/nau.22598. Epub 2014 Mar 28.
    Results Reference
    background
    PubMed Identifier
    18184328
    Citation
    Lucioni A, Bales GT, Lotan TL, McGehee DS, Cook SP, Rapp DE. Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int. 2008 Feb;101(3):366-70. doi: 10.1111/j.1464-410X.2007.07312.x.
    Results Reference
    background
    PubMed Identifier
    15533466
    Citation
    Smith CP, Radziszewski P, Borkowski A, Somogyi GT, Boone TB, Chancellor MB. Botulinum toxin a has antinociceptive effects in treating interstitial cystitis. Urology. 2004 Nov;64(5):871-5; discussion 875. doi: 10.1016/j.urology.2004.06.073.
    Results Reference
    background
    PubMed Identifier
    9334655
    Citation
    Birder LA, Kanai AJ, de Groat WC. DMSO: effect on bladder afferent neurons and nitric oxide release. J Urol. 1997 Nov;158(5):1989-95. doi: 10.1016/s0022-5347(01)64199-5.
    Results Reference
    background
    PubMed Identifier
    5137793
    Citation
    Stewart BH, Branson AC, Hewitt CB, Kiser WS, Straffon RA. The treatment of patients with interstitial cystitis, with special reference to intravesical DMSO. Trans Am Assoc Genitourin Surg. 1971;63:69-74. No abstract available.
    Results Reference
    background

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    Comparison of the Treatment of Refractory Bladder Pain Syndrome With DMSO and DMSO With Botulinum Toxin A

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