Painful Bladder SyndromePhase 4NCT04268810
Prospective Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of PBS/Interstitial Cystitis
A Phase 4 study testing Bladder instillations in people with Painful Bladder Syndrome and Interstitial Cystitis, run by National Multiple Sclerosis Center at 1 site in Belgium.
Trial summary
Painful bladder syndrome/interstitial cystitis (PBS/IC)is a disease of unknown origin with a significant impact on the quality of life. Next to oral treatment with tricyclic antidepressants or pentosan polysulphate, intravesical treatment can be used as well. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Painful Bladder Syndrome, Interstitial Cystitis
- What is being tested?
- Bladder instillations
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteBelgium
- Study dates
- Mar 2010to 31 Dec 2013
- Phase
- Phase 4
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female and male patients from 18-75 years
- A history of symptoms of bladder pain/discomfort described as suprapubic pain related to bladder filling, accompanied by other symptoms such as daytime and/or nighttime frequency in the absence of infection or other pathology, with or without the typical cystoscopic findings of interstitial cystitis
- Patients willing and able to complete the necessary questionnaires
Who cannot join
- Patients with transitional cell carcinoma of the bladder or other significant malignancy
- Pregnant women
- Breastfeading women
- Patients with significant bacteriuria
- Patients with hematuria
- Neurogenic bladder
Show all 21Show fewer
- Patients with indwelling catheters
- Chronic bacterial prostatitis
- Currently receiving or having received investigational drugs thirty (30) days or less prior to screening
- Currently receiving or having had prior therapy with intravesical treatment (eg. Uracyst, Cystistat®, heparin or BCG)
- Receiving therapy for less than three months with antidepressants, antihistaminics, hormonal agonists or antagonists; hence patient not stabilized on therapy. (Stable therapy defined as continuous treatment for at least three months.)
- IC symptoms relieved by antimicrobials, anticholinergics or antispasmodics
- Functional Bladder capacity of greater than 400 ml
- Neurologic disease affecting bladder function; any previous surgery or procedure having affected bladder function
- Current diagnosis of chemical, tuberculous or radiation cystitis
- bladder or lower ureteral calculi
- History of cancer within the last five years other than adequately treated non-melanoma skin cancers
- Active sexual transmitted disease
- Current vaginitis
- Endometriosis
- Any condition/disease which in the opinion of the investigator could interfere with patient compliance and/ or interfere with the interpretation of the treatment results
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Randomised Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of Painful Bladder Syndrome/ Interstitial Cystitis
Painful bladder syndrome/interstitial cystitis (PBS/IC)is a disease of unknown origin with a significant impact on the quality of life. Next to oral treatment with tricyclic antidepressants or pentosan polysulphate, intravesical treatment can be used as well. The purpose of this treatment is to restore the protective lining of the bladder that consists of glycan structures (GAG). Currently only dimethylsulfoxide (DMSO) is FDA approved for this. Several other compounds have been introduced. We want to compare a solution of chondroitin sulphate 2% with the standard DMSO solution. We will compare the patient perception of benefit,but also pain scores, quality of life and micturition diaries.
Read the detailed description
- Introduction
Painful bladder syndrome(PBS) is a syndrome which is poorly understood. Patients usually report suprapubic pain related to bladder filling and also report urinary urgency and frequency. In a subgroup of patients, typical cystoscopic findings can be noted and this defines this subgroup as interstitial cystitis. (Abrams et al. 116-26) The treatment of PBS/IC is empirical. Bladder hydrodistension under anesthesia, tricyclic antidepressants, antihistaminics and intravesical DMSO instillations are the only treatment for which some evidence exists in the literature. More than 150 other treatment modalities have been described . Most of them were poorly studied. (Fall et al. 1-99) Intravesical treatment with DMSO has stood the test of time and is the only FDA approved intravesical treatment of PBS/IC. DMSO however is also used as a solvent in the chemical industry and is in fact used ' off label' in this indication. (Erickson 333-43;Emerson and Perezmarrero A136;Perez-Marrero, Emerson, and Feltis 36-39) One of the theories on which intravesical treatment is based, claims that the glycosaminoglycan layer, which protects the urothelial cells is damaged. DMSO, Chondroitin sulphate, hyaluronic acid and heparin have been used to repair the GAG layer with variable clinical success. (Daha et al. 369-72;Daha et al. 987-90;Riedl et al. 717-21) Chondroitin sulphate seems to be promising, but comparative data are lacking. (Gauruder-Burmester and Popken 355-59;Nickel et al. 56-60;Hauser et al. 2477-82;Nordling and van Ophoven 328-35) Assessing the outcome of such treatments is difficult. Objective parameters such as daytime and nighttime frequency may not always reflect the impact of the condition on the life of the patient.
Patient reported outcome parameters are more frequently used to assess treatments in overactive bladder disease and in painful bladder research. Several validated questionnaires can be used to assess patients with PBS/IC. One of the most frequently used is the O'Leary-Sant questionnaire ( see annex 1). Next to this questionnaire the Global Response Assessment will be used. This is a validated 7 point Likert scale comparing the current status of the patient to the pre-intervention status. This scale has been used in several other studies on PBS/IC. (Nickel et al. 910-18;Baranowski et al. 33-36) Aim To compare the clinical effectiveness of intravesical chondroitin sulphate 2% ( Uracyst ™) and DMSO 50% in the treatment of patients with painful bladder syndrome
- Randomization A central randomization will be used. Participating centers will have to contact the trial office of the dept. of urology of the University Hospitals Leuven to randomize the patient to one or the other treatment, either by telephone 016/346692 or 016/348345 or by mail elza.goossens@uzleuven.be or evelien.vankriekingen@uzleuven.be . A block randomization per center will be done. The randomization list was generated on a web application ( www.randomizer.org) to ensure an unbiased randomization schedule.
- Protocol of administration Patients that are enrolled in the study will receive one intravesical instillation of Uracyst or DMSO a week during 6 weeks. DMSO is prepared as a 50% solution in 50cc physiologic serum. Uracyst will be prepared by the nurse or urologist administering the product.
Uracyst is delivered as a 2% sterile solution in 20cc vials. The instillation is done by a urethral catheterization. The catheter is withdrawn once the fluid has been instilled. The solution is kept in the bladder for at least 30 minutes. A simple instillation protocol is followed, meaning that the patient can move immediately after the instillation of the product. The product is eliminated by spontaneous voiding after 30 minutes.
- Safety Safety is assessed by monitoring adverse events at every visit. Anticipated adverse events are hematuria, algiuria, urinary tract infection and garlic odor ( for DMSO)…
- Statistics Comparison of the mean GRA by T-test will be used for the primary endpoint. Appropriate statistical tests will be used for the secondary variables.
To detect a 0.75 difference on the 7 point Likert scale, with 80% power at 0.05% significance 45 patients will be needed in each group.
- Conditions
- Painful Bladder Syndrome, Interstitial Cystitis
- Being tested
- Bladder instillations
- Keywords
- painful bladder syndrome, interstitial cystitis, chondroitin sulphate, DMSO
- Medical subject headings
- Cystitis, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bladder instillationsProcedure or surgery
bladder instillations with either solution (DMSO or Uracyst)
| Study group | Role | What they receive |
|---|---|---|
| Chondroitin sulphate 2% | Experimental | chondoritin sulphate 2% ( Uracyst) for bladder instillation. One bladeer instillation per week during 6 weeks. Receives: Procedure: Bladder instillations |
| DMSO 50% | Active comparator | DMSO 50% in saline for bladder instillation. One bladder instillation per week during 6 weeks Receives: Procedure: Bladder instillations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global response assessment scale
Primary endpoint: Global response assessment scale.
This is a 7 point scale asking: As compared to when you started the current study, how would you rate your overall bladder symptoms now? Seven response options are given to the patient: Markedly worse, moderately worse, slightly worse, no change, slightly improved, moderately improved, markedly improved.
Measured: 4 weeks after last treatment
Secondary outcomes (5)
Urinary Frequency
- Frequency measured as the mean frequency on a 3 day micturition diary
- Nocturia episodes as the mean number of nocturia episodes on a 3 day micturition diary
- Functional bladder capacity measured as the mean bladder capacity measured on a 3 day micturition diary
- VAS pain scale
- O'Leary -Sant scale
Measured: 4 weeks after last treatment
Nocturia Episodes
Nocturia measured on 3 day micturition diary
Measured: 4 weeks after last treatment
Functional bladder capacity
bladder capacity measured on 3 day micturition diary
Measured: 4 weeks after last treatment
VAS pain scale
visual analogue pain scale
Measured: 4 weeks after last treatment
O'Leary Sant
O'Leary Sant questionnaire score
Measured: 4 weeks after last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study startMar 2010
- Primary completionSep 2013
- Study completion31 Dec 2013
Why it stopped: too many side effect in the control arm (DMSO)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Painful Bladder SyndromeStudies of the same condition, open and under way.
- 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Multiple Sclerosis Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dirk JM De Ridder, MD, PhD, Principal investigator, University Hospitals KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04268810
- Sponsor's protocol ID
- S52212
- Other IDs
- Uracyst study
- Status last verified
- Feb 2020
- First submitted
- 31 Mar 2013
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tutolo M, Ammirati E, Castagna G, Klockaerts K, Plancke H, Ost D, Van der Aa F, De Ridder D. A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroitin sulphate 2% for painful bladder syndrome/interstitial cystitis. Int Braz J Urol. 2017 Jan-Feb;43(1):134-141. doi: 10.1590/S1677-5538.IBJU.2016.0302.
PubMed 28124536
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Randomised Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of Painful Bladder Syndrome/ Interstitial Cystitis
- ClinicalTrials.gov ID
- NCT04268810
- Acronym / sponsor ID
- S52212
- Conditions
- Painful Bladder Syndrome, Interstitial Cystitis
- Keywords
- painful bladder syndrome, interstitial cystitis, chondroitin sulphate, DMSO
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: too many side effect in the control arm (DMSO)
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Multiple Sclerosis CenterUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Sep 2013 (actual)
- Study completion
- 31 Dec 2013 (actual)
- First posted
- 13 Feb 2020 (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.
Painful bladder syndrome/interstitial cystitis (PBS/IC)is a disease of unknown origin with a significant impact on the quality of life. Next to oral treatment with tricyclic antidepressants or pentosan polysulphate, intravesical treatment can be used as well. The purpose of this treatment is to restore the protective lining of the bladder that consists of glycan structures (GAG). Currently only dimethylsulfoxide (DMSO) is FDA approved for this. Several other compounds have been introduced. We want to compare a solution of chondroitin sulphate 2% with the standard DMSO solution. We will compare the patient perception of benefit,but also pain scores, quality of life and micturition diaries.
Detailed description
- Introduction
Painful bladder syndrome(PBS) is a syndrome which is poorly understood. Patients usually report suprapubic pain related to bladder filling and also report urinary urgency and frequency. In a subgroup of patients, typical cystoscopic findings can be noted and this defines this subgroup as interstitial cystitis. (Abrams et al. 116-26) The treatment of PBS/IC is empirical. Bladder hydrodistension under anesthesia, tricyclic antidepressants, antihistaminics and intravesical DMSO instillations are the only treatment for which some evidence exists in the literature. More than 150 other treatment modalities have been described . Most of them were poorly studied. (Fall et al. 1-99) Intravesical treatment with DMSO has stood the test of time and is the only FDA approved intravesical treatment of PBS/IC. DMSO however is also used as a solvent in the chemical industry and is in fact used ' off label' in this indication. (Erickson 333-43;Emerson and Perezmarrero A136;Perez-Marrero, Emerson, and Feltis 36-39) One of the theories on which intravesical treatment is based, claims that the glycosaminoglycan layer, which protects the urothelial cells is damaged. DMSO, Chondroitin sulphate, hyaluronic acid and heparin have been used to repair the GAG layer with variable clinical success. (Daha et al. 369-72;Daha et al. 987-90;Riedl et al. 717-21) Chondroitin sulphate seems to be promising, but comparative data are lacking. (Gauruder-Burmester and Popken 355-59;Nickel et al. 56-60;Hauser et al. 2477-82;Nordling and van Ophoven 328-35) Assessing the outcome of such treatments is difficult. Objective parameters such as daytime and nighttime frequency may not always reflect the impact of the condition on the life of the patient.
Patient reported outcome parameters are more frequently used to assess treatments in overactive bladder disease and in painful bladder research. Several validated questionnaires can be used to assess patients with PBS/IC. One of the most frequently used is the O'Leary-Sant questionnaire ( see annex 1). Next to this questionnaire the Global Response Assessment will be used. This is a validated 7 point Likert scale comparing the current status of the patient to the pre-intervention status. This scale has been used in several other studies on PBS/IC. (Nickel et al. 910-18;Baranowski et al. 33-36) Aim To compare the clinical effectiveness of intravesical chondroitin sulphate 2% ( Uracyst ™) and DMSO 50% in the treatment of patients with painful bladder syndrome
- Randomization A central randomization will be used. Participating centers will have to contact the trial office of the dept. of urology of the University Hospitals Leuven to randomize the patient to one or the other treatment, either by telephone 016/346692 or 016/348345 or by mail elza.goossens@uzleuven.be or evelien.vankriekingen@uzleuven.be . A block randomization per center will be done. The randomization list was generated on a web application ( www.randomizer.org) to ensure an unbiased randomization schedule.
- Protocol of administration Patients that are enrolled in the study will receive one intravesical instillation of Uracyst or DMSO a week during 6 weeks. DMSO is prepared as a 50% solution in 50cc physiologic serum. Uracyst will be prepared by the nurse or urologist administering the product.
Uracyst is delivered as a 2% sterile solution in 20cc vials. The instillation is done by a urethral catheterization. The catheter is withdrawn once the fluid has been instilled. The solution is kept in the bladder for at least 30 minutes. A simple instillation protocol is followed, meaning that the patient can move immediately after the instillation of the product. The product is eliminated by spontaneous voiding after 30 minutes.
- Safety Safety is assessed by monitoring adverse events at every visit. Anticipated adverse events are hematuria, algiuria, urinary tract infection and garlic odor ( for DMSO)…
- Statistics Comparison of the mean GRA by T-test will be used for the primary endpoint. Appropriate statistical tests will be used for the secondary variables.
To detect a 0.75 difference on the 7 point Likert scale, with 80% power at 0.05% significance 45 patients will be needed in each group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chondroitin sulphate 2% | Experimental | Procedure: Bladder instillationschondoritin sulphate 2% ( Uracyst) for bladder instillation. One bladeer instillation per week during 6 weeks. |
| DMSO 50% | Active comparator | Procedure: Bladder instillationsDMSO 50% in saline for bladder instillation. One bladder instillation per week during 6 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Female and male patients from 18-75 years
- A history of symptoms of bladder pain/discomfort described as suprapubic pain related to bladder filling, accompanied by other symptoms such as daytime and/or nighttime frequency in the absence of infection or other pathology, with or without the typical cystoscopic findings of interstitial cystitis
- Patients willing and able to complete the necessary questionnaires
Key exclusion criteria (21 listed)
- Patients with transitional cell carcinoma of the bladder or other significant malignancy
- Pregnant women
- Breastfeading women
- Patients with significant bacteriuria
- Patients with hematuria
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 |
|---|---|---|
| Bladder instillationsbladder instillations with either solution (DMSO or Uracyst) | Procedure or surgery | Chondroitin sulphate 2%, DMSO 50% |
Primary outcome
Global response assessment scale
Time frame: 4 weeks after last treatment
Primary endpoint: Global response assessment scale. This is a 7 point scale asking: As compared to when you started the current study, how would you rate your overall bladder symptoms now? Seven response options are given to the patient: Markedly worse, moderately worse, slightly worse, no change, slightly improved, moderately improved, markedly improved.
5 secondary outcomes
Urinary Frequency
Time frame: 4 weeks after last treatment
Nocturia Episodes
Time frame: 4 weeks after last treatment
Functional bladder capacity
Time frame: 4 weeks after last treatment
VAS pain scale
Time frame: 4 weeks after last treatment
O'Leary Sant
Time frame: 4 weeks after last treatment
Results and safety
The study was stopped early (reason given: too many side effect in the control arm (DMSO)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Background: PubMed 28124536Tutolo M, Ammirati E, Castagna G, Klockaerts K, Plancke H, Ost D, Van der Aa F, De Ridder D. A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroitin sulphate 2% for painful bladder syndrome/interstitial cystitis. Int Braz J Urol. 2017 Jan-Feb;43(1):134-141. doi: 10.1590/S1677-5538.IBJU.2016.0302.
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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.
Dirk JM De Ridder, MD, PhD principal investigator
University Hospitals KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bladder instillations in people with Painful Bladder Syndrome and Interstitial Cystitis, run by National Multiple Sclerosis Center at 1 site in Belgium.
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 3 inclusion and 21 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: stopped early, as of the sponsor's last update on 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early (reason given: too many side effect in the control arm (DMSO)). Results are not available in the source record.
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?
Global response assessment scale (time frame: 4 weeks after last treatment). 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 NCT04268810, which also lists 1 linked publication.
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 13 Feb 2020.