Bladder Pain SyndromeEarly Phase 1NCT03103594
Comparison of the Treatment of Refractory Bladder Pain Syndrome With DMSO and DMSO With Botulinum Toxin A
A Early Phase 1 study testing DMSO and Botox in people with Bladder Pain Syndrome, run by University of Pennsylvania.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Bladder Pain Syndrome
- What is being tested?
- DMSO and Botox
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- No sites listed yet
- Study dates
- Aug 2015to Apr 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
About this study
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.
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.
Read the 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.
- Conditions
- Bladder Pain Syndrome
- Being tested
- DMSO, Botox
- Medical subject headings
- Cystitis, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMSODrug
DMSO will be instilled intravesically.
BotoxDrug
Botox will be instilled intravesically with DMSO.
| Study group | Role | What they receive |
|---|---|---|
| DMSO alone | Active comparator | Half of the patients will undergo DMSO instillation Receives: Drug: DMSO |
| DMSO with Botox | Experimental | The other half will be randomized to DMSO mixed with 200U of botulinum toxin instillation Receives: Drug: DMSO; Drug: Botox |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2017
- Study startAug 2015
- Primary completionAug 2016
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Bladder Pain SyndromeStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Society for Urodynamics and Female Urology
- Responsible party
- Sponsor
- Investigators
- Ariana Smith, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03103594
- Sponsor's protocol ID
- 821084
- Status last verified
- Jun 2017
- First submitted
- 31 Mar 2017
- Last updated
- 9 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share individual participant data.
Publications
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.
PubMed 2719523Cui 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.
PubMed 24676791Lucioni 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.
PubMed 18184328Smith 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.
PubMed 15533466Birder 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.
PubMed 9334655Stewart 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.
PubMed 5137793
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03103594
- Acronym / sponsor ID
- 821084
- Conditions
- Bladder Pain Syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Society for Urodynamics and Female Urology
- Study start
- Aug 2015 (actual)
- Primary completion
- Aug 2016 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 6 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DMSO alone | Active comparator | Drug: DMSOHalf of the patients will undergo DMSO instillation |
| DMSO with Botox | Experimental | Drug: DMSO, Drug: BotoxThe other half will be randomized to DMSO mixed with 200U of botulinum toxin instillation |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DMSODMSO will be instilled intravesically. | Drug | DMSO alone, DMSO with Botox |
| BotoxBotox will be instilled intravesically with DMSO. | Drug | DMSO with Botox |
Primary outcome
Pain Score
Time frame: 6 months
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- Background: PubMed 2719523D'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.
- Background: PubMed 24676791Cui 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.
- Background: PubMed 18184328Lucioni 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.
- Background: PubMed 15533466Smith 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.
- Background: PubMed 9334655Birder 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.
- Background: PubMed 5137793Stewart 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.
- Individual participant dataSharing planned: No. No plan to share individual participant data.
Related trials for Bladder Pain Syndrome
Enrolling by invitationObservational study
Migraine Medication Effects on Urinary Symptoms
Overactive Bladder, Bladder Pain Syndrome
Recruiting
EPPIC: Easing Pelvic Pain Interventions Clinical Research Program
Urologic Chronic Pelvic Pain Syndrome (UCPPS), Interstitial Cystitis
Recruiting
Investigation of PEMF Therapy for Female Patients With IC/BPS
Interstitial Cystitis, Chronic Interstitial Cystitis
Recruiting
Aerobic Exercise and Connective Tissue Massage in Painful Bladder Syndrome
Bladder Pain Syndrome, Painful Bladder Syndrome
RecruitingPhase 2/3
Amniotic Membrane Therapy for Interstitial Cystitis/Painful Bladder Syndrome
Interstitial Cystitis, Painful Bladder Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ariana Smith, MD principal investigator
University of Pennsylvania
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing DMSO and Botox in people with Bladder Pain Syndrome, run by University of Pennsylvania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Score (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03103594, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2017.