Intravesical Botulinum Toxin A Injections in Treatment of Interstitial Cystitis Refractory to Conventional Treatment

NCT01969773 | Completed Phase 2 FDA Drug

• 1 other identifier: TCGHUROL009
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Interstitial Cystitis

Keywords

Botulinum Toxin A (BoNT-A); Interstitial Cystitis

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline and 8 weeks

Secondary Outcomes (9)

• Net change of Patient Perception of global response assessment (GRA)

  Baseline and 8 weeks

• Net change of O'Leary-Sant symptom and problem indexes

  Baseline and 8 weeks

• Net change of the functional bladder capacity (FBC)

  Baseline and 8 weeks

• Net change of the number of urinary frequency

  Baseline and 8 weeks

• Net change of the number of nocturnal

  Baseline and 8 weeks

Study Arms (2)

Botulinum toxin A

EXPERIMENTAL

Patients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA)

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.

Drug: Normal saline instillation

Interventions

Botulinum toxin A DRUG

Patients will be randomly assigned to receive intravesical injection of 100U of BoNT-A (BOTOX, Allergan, Irvine, CA, USA)

Also known as: BoNT-A, BOTOX

Botulinum toxin A

Normal saline instillation DRUG

Patients will be randomly assigned to receive intravesical injection of injection with normal saline.

Also known as: N/S

Control arm-Normal saline instillation

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Age \<18 years old
• Benign or malignant bladder tumors
• Radiation cystitis Tuberculous cystitis
• Bacterial cystitis
• Vaginitis
• 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)

Sponsors & Collaborators

• Buddhist Tzu Chi General Hospital: lead

Study Sites (1)

Buddhist Tzu Chi General Hospital

Hualien City, 970, Taiwan

Location

Related Publications (32)

• 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.

  PMID: 11378041 BACKGROUND

• Payne 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.

  PMID: 15821499 BACKGROUND

• Nickel 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.

  PMID: 15833501 BACKGROUND

• Sant 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.

  PMID: 12913705 BACKGROUND

• Hanno 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.

  PMID: 2926877 BACKGROUND

• Sairanen 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.

  PMID: 15126772 BACKGROUND

• Brady 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.

  PMID: 15049988 BACKGROUND

• Cockayne 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.

  PMID: 11069181 BACKGROUND

• Beltinger 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.

  PMID: 10444403 BACKGROUND

• Cayan 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.

  PMID: 12599022 BACKGROUND

• Steers 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.

  PMID: 16470209 BACKGROUND

• Apostolidis 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.

  PMID: 16094018 BACKGROUND

• Reitz 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.

  PMID: 15041117 BACKGROUND

• Smith CP, Radziszewski P, Borkowski A, Somogyi GT, Boone TB, Chancellor MB. Botulinum toxin a has antinociceptive effects in treating interstitial cystitis. Urology. 2004 Nov;64(5):871-5; discussion 875. doi: 10.1016/j.urology.2004.06.073.

  PMID: 15533466 BACKGROUND

• Kuo 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.

  PMID: 16123573 BACKGROUND

• Giannantoni A, Costantini E, Di Stasi SM, Tascini MC, Bini V, Porena M. Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study. Eur Urol. 2006 Apr;49(4):704-9. doi: 10.1016/j.eururo.2005.12.002. Epub 2006 Jan 4.

  PMID: 16417964 BACKGROUND

• Rapp DE, Turk KW, Bales GT, Cook SP. Botulinum toxin type a inhibits calcitonin gene-related peptide release from isolated rat bladder. J Urol. 2006 Mar;175(3 Pt 1):1138-42. doi: 10.1016/S0022-5347(05)00322-8.

  PMID: 16469640 BACKGROUND

• Chuang YC, Yoshimura N, Huang CC, Chiang PH, Chancellor MB. Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats. J Urol. 2004 Oct;172(4 Pt 1):1529-32. doi: 10.1097/01.ju.0000137844.77524.97.

  PMID: 15371885 BACKGROUND

• Giannantoni A, Di Stasi SM, Nardicchi V, Zucchi A, Macchioni L, Bini V, Goracci G, Porena M. Botulinum-A toxin injections into the detrusor muscle decrease nerve growth factor bladder tissue levels in patients with neurogenic detrusor overactivity. J Urol. 2006 Jun;175(6):2341-4. doi: 10.1016/S0022-5347(06)00258-8.

  PMID: 16697870 BACKGROUND

• Khera M, Somogyi GT, Kiss S, Boone TB, Smith CP. Botulinum toxin A inhibits ATP release from bladder urothelium after chronic spinal cord injury. Neurochem Int. 2004 Dec;45(7):987-93. doi: 10.1016/j.neuint.2004.06.001.

  PMID: 15337297 BACKGROUND

• Kuo HC. Clinical effects of suburothelial injection of botulinum A toxin on patients with nonneurogenic detrusor overactivity refractory to anticholinergics. Urology. 2005 Jul;66(1):94-8. doi: 10.1016/j.urology.2005.02.002.

  PMID: 15992869 BACKGROUND

• Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004 Jan;107(1-2):125-33. doi: 10.1016/j.pain.2003.10.008.

  PMID: 14715398 BACKGROUND

• Giannantoni A, Porena M, Costantini E, Zucchi A, Mearini L, Mearini E. Botulinum A toxin intravesical injection in patients with painful bladder syndrome: 1-year followup. J Urol. 2008 Mar;179(3):1031-4. doi: 10.1016/j.juro.2007.10.032. Epub 2008 Jan 18.

  PMID: 18206941 BACKGROUND

• Lubeck DP, Whitmore K, Sant GR, Alvarez-Horine S, Lai C. Psychometric validation of the O'leary-Sant interstitial cystitis symptom index in a clinical trial of pentosan polysulfate sodium. Urology. 2001 Jun;57(6 Suppl 1):62-6. doi: 10.1016/s0090-4295(01)01126-8.

  PMID: 11378052 BACKGROUND

• Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21(2):167-78. doi: 10.1002/nau.10052. No abstract available.

  PMID: 11857671 BACKGROUND

• Vizzard MA. Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. Exp Neurol. 2000 Jan;161(1):273-84. doi: 10.1006/exnr.1999.7254.

  PMID: 10683293 BACKGROUND

• Parsons CL, Housley T, Schmidt JD, Lebow D. Treatment of interstitial cystitis with intravesical heparin. Br J Urol. 1994 May;73(5):504-7. doi: 10.1111/j.1464-410x.1994.tb07634.x.

  PMID: 8012771 BACKGROUND

• Chung SD, Kuo YC, Kuo HC. Intravesical onabotulinumtoxinA injections for refractory painful bladder syndrome. Pain Physician. 2012 May-Jun;15(3):197-202.

  PMID: 22622903 BACKGROUND

• Seki S, Erickson KA, Seki M, Nishizawa O, Igawa Y, Ogawa T, de Groat WC, Chancellor MB, Yoshimura N. Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation. Am J Physiol Renal Physiol. 2005 Mar;288(3):F466-73. doi: 10.1152/ajprenal.00274.2004.

  PMID: 15692058 BACKGROUND

• Dell JR, Parsons CL. Multimodal therapy for interstitial cystitis. J Reprod Med. 2004 Mar;49(3 Suppl):243-52.

  PMID: 15088863 BACKGROUND

• Liu HT, Kuo HC. Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007 Sep;70(3):463-8. doi: 10.1016/j.urology.2007.04.038.

  PMID: 17905097 BACKGROUND

• Imamura M, Scott NW, Wallace SA, Ogah JA, Ford AA, Dubos YA, Brazzelli M. Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis. Cochrane Database Syst Rev. 2020 Jul 30;7(7):CD013325. doi: 10.1002/14651858.CD013325.pub2.

  PMID: 32734597 DERIVED

MeSH Terms

Conditions

Cystitis, Interstitial

Interventions

Botulinum Toxins, Type A; incobotulinumtoxinA

Condition Hierarchy (Ancestors)

Cystitis; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Hann-Chorng Kuo, M.D.

  Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The attending doctors, patients, and study nurses did not know which solution was injected to their bladders, to keep the study in a double-blind condition.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Urology

Model Details: The patients were allocated to the treatment or control group by permuted block randomization code in a 2:1 ratio

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 25, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 17, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)