Interstitial CystitisPhase 2NCT01969773
Intravesical Botulinum Toxin A Injections in Treatment of Interstitial Cystitis Refractory to Conventional Treatment
A Phase 2 study testing Botulinum toxin A and Normal saline instillation in people with Interstitial Cystitis, run by Buddhist Tzu Chi General Hospital at 1 site in Taiwan.
Trial summary
This study was designed in a multicenter, randomized, double-blind, placebo controlled trial to test the actual therapeutic effects of intravesical BoNTA injection. The results of this study might provide clinical evidence for a better therapeutic regimen in the treatment of IC/PBS. Read more about this study
- Who is it for?
- Ages 20 to 85 years
- Conditions the study is for
- Interstitial Cystitis
- What is being tested?
- Botulinum toxin A and Normal saline instillation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- Dec 2012to Dec 2014
- Phase
- Phase 2
- 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 20 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with IC/PBS who have failed conventional treatments for at least 6 months will be enrolled.
- A diagnosis of IC/PBS has been established based on characteristic symptoms and cystoscopic findings of glomerulations, petechia, or mucosal fissures after hydrodistention.
- All patients have been treated with at least two types of treatment modalities including non-steroid anti-inflammatory drugs, oral pentosan polysulfate sodium (PPS), intravesical instillation of heparin, hyaluronic acid, or tricyclic antidepressant for at least 6 months but the symptoms remained unchanged or relapsed.
Who cannot join
- Automatic exclusions:
- Age <18 years old
- Benign or malignant bladder tumors
- Radiation cystitis Tuberculous cystitis
- Bacterial cystitis
- Vaginitis
Show all 41Show fewer
- Cyclophosphamide cystitis
- Symptomatic urethral diverticulum
- Uterine, cervical, vaginal, or urethral cancer
- Active herpes
- Bladder or lower ureteral calculi
- Waking frequency <5 times in 12 hours
- Nocturia <2 times
- Symptoms relieved by antibiotics, urinary antiseptics, urinary analgesics (for example phenazopyridine hydrochloride)
- Duration < 12 months
- Involuntary bladder contractions (urodynamics)
- Capacity > 400ml, absence of sensory urgency
- Automatic inclusions:
- 1.Hunner's ulcer
- Positive factors: (two positive factors are necessary for inclusion)
- Pain on bladder filling relieved by emptying
- Pain (suprapubic, pelvic, urethral, vaginal or peripheral)
- Glomerulations on endoscopy
- Decreased compliance on cystometrogram
- Bladder distention is defined arbitrarily as 80 cm water pressure for 1 minute
- Use of Anticholinergic drugs, for the treatment of lower urinary tract symptoms who have an effect.
- Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up.
- Patients with bladder outlet obstruction on enrollment.
- Patients with urinary retention, PVR≥150 ml.
- Patients with uncontrolled confirmed diagnosis of acute urinary tract infection.
- Patients have laboratory abnormalities at screening including:
- Alanine aminotransferase (ALT) > 3 x upper limit of normal range
- Aspartate aminotransferase (AST) > 3 x upper limit of normal range.
- Patients have abnormal serum creatinine level > 2 x upper limit of normal range.
- Can not be used in the treatment of patients with transurethral catheter treatment.
- Pregnant and lactating women or women who intend to become pregnant during the study or have myasthenia gravis, Eaton Lambert syndrome.
- Patients with any other serious disease or condition considered by the investigator not suitable for entry into the trial.
- Patients participated investigational drug trial within 1 month before entering this study.
- Written informed consent has been obtained.
- Patient who did not complete the 3-day micturition diary according to the instruction.
- Intestinal bladder augmentation patients receive angioplasty for the treatment of overactive bladder.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intravesical Botulinum Toxin A Injection in Treatment of Interstitial Cystitis Refractory to Conventional Treatment - A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial
This study was designed in a multicenter, randomized, double-blind, placebo controlled trial to test the actual therapeutic effects of intravesical BoNTA injection. The results of this study might provide clinical evidence for a better therapeutic regimen in the treatment of IC/PBS.
Read the detailed description
Background: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating chronic disease of unknown etiology. Current treatments are usually unsuccessful in completely eradicating bladder pain and increasing bladder capacity. Although investigations on this topic have been enthusiastically performed, the etiology of IC/PBS remains unknown. Treatment based on single pathophysiology such as urothelial damage or neurogenic inflammation might not enough to eradicate the cascade of pathologies of IC/PBS.
Inhibition of neuroplasticity of the sensory fibers in the suburothelial space by intravesical BoNT-A injections might have good therapeutic targeting on pain and sensory urgency in patients with IC/PBS. In recent basic researches, BoNT-A has been shown to inhibit not only the release of acetylcholine and norepinephrine, but also that of nerve growth factor, adenosine triphosphate, substance P and calcitonin gene-related peptide from the nerve fibers and urothelium. This study was designed in a multicenter, randomized, double-blind, placebo controlled trial to test the actual therapeutic effects of intravesical BoNT-A injection on IC/PBS. The results of this study might provide clinical evidence for a better therapeutic regimen in the treatment of IC/PBS.
Materials and Methods: A total of 90 patients with IC/PBS who have failed conventional treatments for at least 6 months will be enrolled in this study. A diagnosis of IC/PBS has been established based on characteristic symptoms and cystoscopic findings of glomerulations, petechia, or mucosal fissures after hydrodistention. They will be investigated thoroughly on enrollment and will be excluded if not meeting the inclusion criteria of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). However, in this study the patients with Hunner's ulcer will not be included because previous study has shown that ulcer type IC/PBS does not respond to intravesical BoNT-A injection.
A 3-day voiding diary for functional bladder capacity, urinary frequency and nocturnal, O'Leary-Sant symptom and problem indexes, visual analog score (VAS), and videourodynamic parameters and potassium chloride (KCl) sensitivity test will be used to assess the therapeutic efficacy. Patients will be informed of the possible complications associated with BoNT-A injection such as generalized muscle weakness, difficult urination, transient urinary retention, or urinary tract infections. Eligible patients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA) (the treatment group) or injection with normal saline (control group). The intravesical injection will be performed immediately followed by cystoscopic hydrodistention under intravenous general anesthesia in the operation room.
Blood (10ml) and urine samples (30ml) will be collected before intravesical injection and after bladder hydrodistention. Bladder wall biopsies will also be performed after hydrodistention. The patients will be allocated to treatment or control group by the permuted block randomization code in 2:1 ratio, which is centrally controlled by a clinical pharmacist who prepares the solution for injection. Each vial of BoNT-A will be diluted with 10 ml of normal saline, resulting in 10U BoNT-A per 1.0 ml. Patients receive 20 suburothelial injections of BoNT-A solution or normal saline, each injection site receives 5U or saline in 0.5 ml. After the BoNT-A injections, patients will be followed up in the outpatient clinic 2 weeks and 4 weeks later. Then the patients will be followed up at out-patient clinic at 2 weeks, 4 weeks and 12 weeks. The primary end-point of this study is the reduction of bladder pain at 12-week follow-up. If patient has a reduction of VAS pain score of 2 or more, they will be considered as successfully treated. The treatment outcome will also be assessed by the global response assessment (GRA) to evaluate the overall perception of treatment result. The result will be considered as excellent when patients report improvement in the GRA by >2 or patients become free of bladder pain (VAS=0). Data will be compared between treatment and placebo groups. A p-value of less than 0.05 will be considered statistically significant.
Cystoscopy and bladder biopsy will be performed and sent for pathological examination and urological laboratory for investigations. The urine and serum biomarkers (NGF) and urothelial dysfunction markers (TUNEL for apoptosis, Ki-67 for proliferation, tryptase staining for mast cell activity, E-cadherin and zonula occludens-1 for junction protein expression) will be assessed to investigate the severity of urothelial dysfunction and chronic inflammation presented in these diseased bladders. Furthermore, the inflammatory protein assay such as TNFα, IL-6, IL-8 or TGF-beta will also be measured by protein array and western blotting. The urine and blood samples will be collected at baseline, 4 weeks, and end-point (12 weeks) in both treatment and controlled patients. The changes of urine and serum nerve growth factor (NGF) and cytokines (such as IL-1 beta, IL-6, IL-8, TNF-alpha) will be compared within group and between groups to provide laboratory evidence of decrease of bladder inflammation in IC/PBS. The changes of NGF and cytokines levels after BoNT-A injection treatments will also be compared in patients who respond and not respond to the treatment given. Urinary and serum NGF and cytokines levels were measured by the ELISA method.
Expected Results: The results of this study may demonstrate that intravesical injection of BoNT-A has a better clinical effect to provide greater pain relief and increase bladder capacity in patients with IC/PBS compared to the patients who received saline injection treatment. The clinical effect of BoNT-A on IC/PBS might be further reflected by the reduction of the serum or urinary NGF and cytokines levels.
- Conditions
- Interstitial Cystitis
- Being tested
- Botulinum toxin A, Normal saline instillation
- Keywords
- Botulinum Toxin A (BoNT-A), Interstitial Cystitis
- Medical subject headings
- Cystitis, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum toxin ADrug
Also called BoNT-A, BOTOX
Patients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA)
Normal saline instillationDrug
Also called N/S
Patients will be randomly assigned to receive intravesical injection of injection with normal saline.
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin A | Experimental | Patients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA) Receives: Drug: Botulinum toxin A |
| Control arm-Normal saline instillation | Placebo comparator | Patients will be randomly assigned to receive intravesical injection of injection with normal saline. Receives: Drug: Normal saline instillation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Net change of Patient Perception of Visual Analogue Scale (VAS)
Efficacy:
The primary end-point of this study is the reduction of bladder pain at 8-week follow-up. If patient has a reduction of VAS pain score of 2 or more, they will be considered as successfully treated at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Secondary outcomes (9)
Net change of Patient Perception of global response assessment (GRA)
Efficacy:
The treatment outcome will be assessed by the global response assessment (GRA) to evaluate the overall perception of treatment resultant at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of O'Leary-Sant symptom and problem indexes
Efficacy:
The IC symptoms will be assessed by the O'Leary-Sant symptom and problem indexes at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of the functional bladder capacity (FBC)
Efficacy:
Patients will be requested to keep a 3-day voiding diary prior to treatment to record the functional bladder capacity (FBC). Then the patients will be followed up at out-patient clinic at 8 weeks.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of the number of urinary frequency
Efficacy:
Patients will be requested to keep a 3-day voiding diary prior to treatment to record the number of urinary frequency at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of the number of nocturnal
Efficacy:
Patients will be requested to keep a 3-day voiding diary prior to treatment to record the number of nocturnal at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of the Quality of Life (QoL)
Efficacy:
Efficacy measured the net change of the Quality of Life (QoL) at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of the maximal flow rate (Qmax)
Efficacy:
Efficacy measured the net change of the maximal flow rate (Qmax) at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of the voided volume
Efficacy:
Efficacy measured the net change of the voided volume at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Net change of the residual urine volume (PVR)
Efficacy:
Efficacy measured the net change of the residual urine volume (PVR) at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups.
Safety:
Systemic adverse events
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2013 (estimated)
- Study startDec 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Interstitial CystitisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- The patients were allocated to the treatment or control group by permuted block randomization code in a 2:1 ratio
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Buddhist Tzu Chi General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hann-Chorng Kuo, Buddhist Tzu Chi General Hospital
- Investigators
- Hann-Chorng Kuo, M.D., Principal investigator, Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01969773
- Sponsor's protocol ID
- TCGHUROL009
- Status last verified
- Feb 2017
- First submitted
- 22 Oct 2013
- Last updated
- 17 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD was not planned to share
Publications
Hanno PM, Sant GR. Clinical highlights of the National Institute of Diabetes and Digestive and Kidney Diseases/Interstitial Cystitis Association scientific conference on interstitial cystitis. Urology. 2001 Jun;57(6 Suppl 1):2-6. doi: 10.1016/s0090-4295(01)01112-8.
PubMed 11378041Payne CK, Mosbaugh PG, Forrest JB, Evans RJ, Whitmore KE, Antoci JP, Perez-Marrero R, Jacoby K, Diokno AC, O'Reilly KJ, Griebling TL, Vasavada SP, Yu AS, Frumkin LR; ICOS RTX Study Group (Resiniferatoxin Treatment for Interstitial Cystitis). Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. J Urol. 2005 May;173(5):1590-4. doi: 10.1097/01.ju.0000154631.92150.ef.
PubMed 15821499Nickel JC, Barkin J, Forrest J, Mosbaugh PG, Hernandez-Graulau J, Kaufman D, Lloyd K, Evans RJ, Parsons CL, Atkinson LE; Elmiron Study Group. Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. Urology. 2005 Apr;65(4):654-8. doi: 10.1016/j.urology.2004.10.071.
PubMed 15833501Sant GR, Propert KJ, Hanno PM, Burks D, Culkin D, Diokno AC, Hardy C, Landis JR, Mayer R, Madigan R, Messing EM, Peters K, Theoharides TC, Warren J, Wein AJ, Steers W, Kusek JW, Nyberg LM; Interstitial Cystitis Clinical Trials Group. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003 Sep;170(3):810-5. doi: 10.1097/01.ju.0000083020.06212.3d.
PubMed 12913705Hanno PM, Buehler J, Wein AJ. Use of amitriptyline in the treatment of interstitial cystitis. J Urol. 1989 Apr;141(4):846-8. doi: 10.1016/s0022-5347(17)41029-9.
PubMed 2926877Sairanen J, Forsell T, Ruutu M. Long-term outcome of patients with interstitial cystitis treated with low dose cyclosporine A. J Urol. 2004 Jun;171(6 Pt 1):2138-41. doi: 10.1097/01.ju.0000125139.91203.7a.
PubMed 15126772Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, Freeman A, Scaravilli F, Fowler CJ, Anand P. Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int. 2004 Apr;93(6):770-6. doi: 10.1111/j.1464-410X.2003.04722.x.
PubMed 15049988Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford AP. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature. 2000 Oct 26;407(6807):1011-5. doi: 10.1038/35039519.
PubMed 11069181Beltinger J, McKaig BC, Makh S, Stack WA, Hawkey CJ, Mahida YR. Human colonic subepithelial myofibroblasts modulate transepithelial resistance and secretory response. Am J Physiol. 1999 Aug;277(2):C271-9. doi: 10.1152/ajpcell.1999.277.2.C271.
PubMed 10444403Cayan S, Coskun B, Bozlu M, Acar D, Akbay E, Ulusoy E. Botulinum toxin type A may improve bladder function in a rat chemical cystitis model. Urol Res. 2003 Feb;30(6):399-404. doi: 10.1007/s00240-002-0291-0. Epub 2003 Jan 21.
PubMed 12599022Steers WD, Tuttle JB. Mechanisms of Disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat Clin Pract Urol. 2006 Feb;3(2):101-10. doi: 10.1038/ncpuro0408.
PubMed 16470209Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, Dasgupta P, Fowler CJ, Anand P. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005 Sep;174(3):977-82; discussion 982-3. doi: 10.1097/01.ju.0000169481.42259.54.
PubMed 16094018Reitz A, Stohrer M, Kramer G, Del Popolo G, Chartier-Kastler E, Pannek J, Burgdorfer H, Gocking K, Madersbacher H, Schumacher S, Richter R, von Tobel J, Schurch B. European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. Eur Urol. 2004 Apr;45(4):510-5. doi: 10.1016/j.eururo.2003.12.004.
PubMed 15041117Smith 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 15533466Kuo HC. Preliminary results of suburothelial injection of botulinum a toxin in the treatment of chronic interstitial cystitis. Urol Int. 2005;75(2):170-4. doi: 10.1159/000087173.
PubMed 16123573
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravesical Botulinum Toxin A Injection in Treatment of Interstitial Cystitis Refractory to Conventional Treatment - A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT01969773
- Acronym / sponsor ID
- TCGHUROL009
- Conditions
- Interstitial Cystitis
- Keywords
- Botulinum Toxin A (BoNT-A), Interstitial Cystitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Buddhist Tzu Chi General HospitalUniversity, hospital or other
- Study start
- Dec 2012 (actual)
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 25 Oct 2013 (estimated)
- 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.
This study was designed in a multicenter, randomized, double-blind, placebo controlled trial to test the actual therapeutic effects of intravesical BoNTA injection. The results of this study might provide clinical evidence for a better therapeutic regimen in the treatment of IC/PBS.
Detailed description
Background: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating chronic disease of unknown etiology. Current treatments are usually unsuccessful in completely eradicating bladder pain and increasing bladder capacity. Although investigations on this topic have been enthusiastically performed, the etiology of IC/PBS remains unknown. Treatment based on single pathophysiology such as urothelial damage or neurogenic inflammation might not enough to eradicate the cascade of pathologies of IC/PBS.
Inhibition of neuroplasticity of the sensory fibers in the suburothelial space by intravesical BoNT-A injections might have good therapeutic targeting on pain and sensory urgency in patients with IC/PBS. In recent basic researches, BoNT-A has been shown to inhibit not only the release of acetylcholine and norepinephrine, but also that of nerve growth factor, adenosine triphosphate, substance P and calcitonin gene-related peptide from the nerve fibers and urothelium. This study was designed in a multicenter, randomized, double-blind, placebo controlled trial to test the actual therapeutic effects of intravesical BoNT-A injection on IC/PBS. The results of this study might provide clinical evidence for a better therapeutic regimen in the treatment of IC/PBS.
Materials and Methods: A total of 90 patients with IC/PBS who have failed conventional treatments for at least 6 months will be enrolled in this study. A diagnosis of IC/PBS has been established based on characteristic symptoms and cystoscopic findings of glomerulations, petechia, or mucosal fissures after hydrodistention. They will be investigated thoroughly on enrollment and will be excluded if not meeting the inclusion criteria of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). However, in this study the patients with Hunner's ulcer will not be included because previous study has shown that ulcer type IC/PBS does not respond to intravesical BoNT-A injection.
A 3-day voiding diary for functional bladder capacity, urinary frequency and nocturnal, O'Leary-Sant symptom and problem indexes, visual analog score (VAS), and videourodynamic parameters and potassium chloride (KCl) sensitivity test will be used to assess the therapeutic efficacy. Patients will be informed of the possible complications associated with BoNT-A injection such as generalized muscle weakness, difficult urination, transient urinary retention, or urinary tract infections. Eligible patients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA) (the treatment group) or injection with normal saline (control group). The intravesical injection will be performed immediately followed by cystoscopic hydrodistention under intravenous general anesthesia in the operation room.
Blood (10ml) and urine samples (30ml) will be collected before intravesical injection and after bladder hydrodistention. Bladder wall biopsies will also be performed after hydrodistention. The patients will be allocated to treatment or control group by the permuted block randomization code in 2:1 ratio, which is centrally controlled by a clinical pharmacist who prepares the solution for injection. Each vial of BoNT-A will be diluted with 10 ml of normal saline, resulting in 10U BoNT-A per 1.0 ml. Patients receive 20 suburothelial injections of BoNT-A solution or normal saline, each injection site receives 5U or saline in 0.5 ml. After the BoNT-A injections, patients will be followed up in the outpatient clinic 2 weeks and 4 weeks later. Then the patients will be followed up at out-patient clinic at 2 weeks, 4 weeks and 12 weeks. The primary end-point of this study is the reduction of bladder pain at 12-week follow-up. If patient has a reduction of VAS pain score of 2 or more, they will be considered as successfully treated. The treatment outcome will also be assessed by the global response assessment (GRA) to evaluate the overall perception of treatment result. The result will be considered as excellent when patients report improvement in the GRA by >2 or patients become free of bladder pain (VAS=0). Data will be compared between treatment and placebo groups. A p-value of less than 0.05 will be considered statistically significant.
Cystoscopy and bladder biopsy will be performed and sent for pathological examination and urological laboratory for investigations. The urine and serum biomarkers (NGF) and urothelial dysfunction markers (TUNEL for apoptosis, Ki-67 for proliferation, tryptase staining for mast cell activity, E-cadherin and zonula occludens-1 for junction protein expression) will be assessed to investigate the severity of urothelial dysfunction and chronic inflammation presented in these diseased bladders. Furthermore, the inflammatory protein assay such as TNFα, IL-6, IL-8 or TGF-beta will also be measured by protein array and western blotting. The urine and blood samples will be collected at baseline, 4 weeks, and end-point (12 weeks) in both treatment and controlled patients. The changes of urine and serum nerve growth factor (NGF) and cytokines (such as IL-1 beta, IL-6, IL-8, TNF-alpha) will be compared within group and between groups to provide laboratory evidence of decrease of bladder inflammation in IC/PBS. The changes of NGF and cytokines levels after BoNT-A injection treatments will also be compared in patients who respond and not respond to the treatment given. Urinary and serum NGF and cytokines levels were measured by the ELISA method.
Expected Results: The results of this study may demonstrate that intravesical injection of BoNT-A has a better clinical effect to provide greater pain relief and increase bladder capacity in patients with IC/PBS compared to the patients who received saline injection treatment. The clinical effect of BoNT-A on IC/PBS might be further reflected by the reduction of the serum or urinary NGF and cytokines levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The patients were allocated to the treatment or control group by permuted block randomization code in a 2:1 ratio
| Arm | Type | Receives |
|---|---|---|
| Botulinum toxin A | Experimental | Drug: Botulinum toxin APatients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA) |
| Control arm-Normal saline instillation | Placebo comparator | Drug: Normal saline instillationPatients will be randomly assigned to receive intravesical injection of injection with normal saline. |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with IC/PBS who have failed conventional treatments for at least 6 months will be enrolled.
- A diagnosis of IC/PBS has been established based on characteristic symptoms and cystoscopic findings of glomerulations, petechia, or mucosal fissures after hydrodistention.
- All patients have been treated with at least two types of treatment modalities including non-steroid anti-inflammatory drugs, oral pentosan polysulfate sodium (PPS), intravesical instillation of heparin, hyaluronic acid, or tricyclic antidepressant for at least 6 months but the symptoms remained unchanged or relapsed.
Key exclusion criteria (41 listed)
- Automatic exclusions:
- Automatic inclusions:
- 1.Hunner's ulcer
- Positive factors: (two positive factors are necessary for inclusion)
- Use of Anticholinergic drugs, for the treatment of lower urinary tract symptoms who have an effect.
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 |
|---|---|---|
| Botulinum toxin AAlso: BoNT-A, BOTOXPatients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA) | Drug | Botulinum toxin A |
| Normal saline instillationAlso: N/SPatients will be randomly assigned to receive intravesical injection of injection with normal saline. | Drug | Control arm-Normal saline instillation |
Primary outcome
Net change of Patient Perception of Visual Analogue Scale (VAS)
Time frame: Baseline and 8 weeks
Efficacy: The primary end-point of this study is the reduction of bladder pain at 8-week follow-up. If patient has a reduction of VAS pain score of 2 or more, they will be considered as successfully treated at baseline and 8 weeks after BoNT-A injection within and between the treatment group and control groups. Safety: Systemic adverse events
9 secondary outcomes
Net change of Patient Perception of global response assessment (GRA)
Time frame: Baseline and 8 weeks
Net change of O'Leary-Sant symptom and problem indexes
Time frame: Baseline and 8 weeks
Net change of the functional bladder capacity (FBC)
Time frame: Baseline and 8 weeks
Net change of the number of urinary frequency
Time frame: Baseline and 8 weeks
Net change of the number of nocturnal
Time frame: Baseline and 8 weeks
Net change of the Quality of Life (QoL)
Time frame: Baseline and 8 weeks
Net change of the maximal flow rate (Qmax)
Time frame: Baseline and 8 weeks
Net change of the voided volume
Time frame: Baseline and 8 weeks
Net change of the residual urine volume (PVR)
Time frame: Baseline and 8 weeks
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 17 Feb 2017.
- Background: PubMed 11378041Hanno PM, Sant GR. Clinical highlights of the National Institute of Diabetes and Digestive and Kidney Diseases/Interstitial Cystitis Association scientific conference on interstitial cystitis. Urology. 2001 Jun;57(6 Suppl 1):2-6. doi: 10.1016/s0090-4295(01)01112-8.
- Background: PubMed 15821499Payne CK, Mosbaugh PG, Forrest JB, Evans RJ, Whitmore KE, Antoci JP, Perez-Marrero R, Jacoby K, Diokno AC, O'Reilly KJ, Griebling TL, Vasavada SP, Yu AS, Frumkin LR; ICOS RTX Study Group (Resiniferatoxin Treatment for Interstitial Cystitis). Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. J Urol. 2005 May;173(5):1590-4. doi: 10.1097/01.ju.0000154631.92150.ef.
- Background: PubMed 15833501Nickel JC, Barkin J, Forrest J, Mosbaugh PG, Hernandez-Graulau J, Kaufman D, Lloyd K, Evans RJ, Parsons CL, Atkinson LE; Elmiron Study Group. Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. Urology. 2005 Apr;65(4):654-8. doi: 10.1016/j.urology.2004.10.071.
- Background: PubMed 12913705Sant GR, Propert KJ, Hanno PM, Burks D, Culkin D, Diokno AC, Hardy C, Landis JR, Mayer R, Madigan R, Messing EM, Peters K, Theoharides TC, Warren J, Wein AJ, Steers W, Kusek JW, Nyberg LM; Interstitial Cystitis Clinical Trials Group. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003 Sep;170(3):810-5. doi: 10.1097/01.ju.0000083020.06212.3d.
- Background: PubMed 2926877Hanno PM, Buehler J, Wein AJ. Use of amitriptyline in the treatment of interstitial cystitis. J Urol. 1989 Apr;141(4):846-8. doi: 10.1016/s0022-5347(17)41029-9.
- Background: PubMed 15126772Sairanen J, Forsell T, Ruutu M. Long-term outcome of patients with interstitial cystitis treated with low dose cyclosporine A. J Urol. 2004 Jun;171(6 Pt 1):2138-41. doi: 10.1097/01.ju.0000125139.91203.7a.
- Background: PubMed 15049988Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, Freeman A, Scaravilli F, Fowler CJ, Anand P. Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int. 2004 Apr;93(6):770-6. doi: 10.1111/j.1464-410X.2003.04722.x.
- Background: PubMed 11069181Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford AP. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature. 2000 Oct 26;407(6807):1011-5. doi: 10.1038/35039519.
- Background: PubMed 10444403Beltinger J, McKaig BC, Makh S, Stack WA, Hawkey CJ, Mahida YR. Human colonic subepithelial myofibroblasts modulate transepithelial resistance and secretory response. Am J Physiol. 1999 Aug;277(2):C271-9. doi: 10.1152/ajpcell.1999.277.2.C271.
- Background: PubMed 12599022Cayan S, Coskun B, Bozlu M, Acar D, Akbay E, Ulusoy E. Botulinum toxin type A may improve bladder function in a rat chemical cystitis model. Urol Res. 2003 Feb;30(6):399-404. doi: 10.1007/s00240-002-0291-0. Epub 2003 Jan 21.
- Background: PubMed 16470209Steers WD, Tuttle JB. Mechanisms of Disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat Clin Pract Urol. 2006 Feb;3(2):101-10. doi: 10.1038/ncpuro0408.
- Background: PubMed 16094018Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, Dasgupta P, Fowler CJ, Anand P. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005 Sep;174(3):977-82; discussion 982-3. doi: 10.1097/01.ju.0000169481.42259.54.
- Individual participant dataSharing planned: No. IPD was not planned to share
Related trials for Interstitial Cystitis
Active, not recruiting
Medtronic Hugo™ Robotic Assisted Surgery (RAS) System in Urologic Surgery (Expand URO)
Bladder Cancer, Prostate Cancer
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
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.
Hann-Chorng Kuo, M.D. principal investigator
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Botulinum toxin A and Normal saline instillation in people with Interstitial Cystitis, run by Buddhist Tzu Chi General Hospital at 1 site in Taiwan.
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 41 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 17 Feb 2017. 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 Taiwan. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Net change of Patient Perception of Visual Analogue Scale (VAS) (time frame: Baseline and 8 weeks). 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 NCT01969773, which also lists 32 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 17 Feb 2017.