Prospective Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of PBS/Interstitial Cystitis
Primary Purpose
Painful Bladder Syndrome, Interstitial Cystitis
Status
Terminated
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Bladder instillations
Sponsored by
About this trial
This is an interventional treatment trial for Painful Bladder Syndrome focused on measuring painful bladder syndrome, interstitial cystitis, chondroitin sulphate, DMSO
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Urology, University Hospitals KU Leuven
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Chondroitin sulphate 2%
DMSO 50%
Arm Description
chondoritin sulphate 2% ( Uracyst) for bladder instillation. One bladeer instillation per week during 6 weeks.
DMSO 50% in saline for bladder instillation. One bladder instillation per week during 6 weeks
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Nocturia Episodes
Nocturia measured on 3 day micturition diary
Functional bladder capacity
bladder capacity measured on 3 day micturition diary
VAS pain scale
visual analogue pain scale
O'Leary Sant
O'Leary Sant questionnaire score
Full Information
NCT ID
NCT04268810
First Posted
March 31, 2013
Last Updated
February 11, 2020
Sponsor
National Multiple Sclerosis Center
1. Study Identification
Unique Protocol Identification Number
NCT04268810
Brief Title
Prospective Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of PBS/Interstitial Cystitis
Official Title
Prospective Randomised Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of Painful Bladder Syndrome/ Interstitial Cystitis
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
too many side effect in the control arm (DMSO)
Study Start Date
March 2010 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
December 31, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Multiple Sclerosis Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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
A. 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
B. 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.
C. 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.
D. 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)…
E. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Painful Bladder Syndrome, Interstitial Cystitis
Keywords
painful bladder syndrome, interstitial cystitis, chondroitin sulphate, DMSO
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Chondroitin sulphate 2%
Arm Type
Experimental
Arm Description
chondoritin sulphate 2% ( Uracyst) for bladder instillation. One bladeer instillation per week during 6 weeks.
Arm Title
DMSO 50%
Arm Type
Active Comparator
Arm Description
DMSO 50% in saline for bladder instillation. One bladder instillation per week during 6 weeks
Intervention Type
Procedure
Intervention Name(s)
Bladder instillations
Intervention Description
bladder instillations with either solution (DMSO or Uracyst)
Primary Outcome Measure Information:
Title
Global response assessment scale
Description
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.
Time Frame
4 weeks after last treatment
Secondary Outcome Measure Information:
Title
Urinary Frequency
Description
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
Time Frame
4 weeks after last treatment
Title
Nocturia Episodes
Description
Nocturia measured on 3 day micturition diary
Time Frame
4 weeks after last treatment
Title
Functional bladder capacity
Description
bladder capacity measured on 3 day micturition diary
Time Frame
4 weeks after last treatment
Title
VAS pain scale
Description
visual analogue pain scale
Time Frame
4 weeks after last treatment
Title
O'Leary Sant
Description
O'Leary Sant questionnaire score
Time Frame
4 weeks after last treatment
Other Pre-specified Outcome Measures:
Title
Drop-out
Description
patients refusing further treatment because of intolerance to the intravesical treatment of by lack of improvement
Time Frame
any time during study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk JM De Ridder, MD, PhD
Organizational Affiliation
University Hospitals KU Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
Urology, University Hospitals KU Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
12. IPD Sharing Statement
Citations:
PubMed Identifier
28124536
Citation
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.
Results Reference
background
Learn more about this trial
Prospective Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of PBS/Interstitial Cystitis
We'll reach out to this number within 24 hrs