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
About this trial
This is an interventional treatment trial for Bladder Pain Syndrome
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
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
NCT ID
NCT03103594
First Posted
March 31, 2017
Last Updated
June 8, 2017
Sponsor
University of Pennsylvania
Collaborators
Society for Urodynamics and Female Urology
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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