Evaluation of Response to Use of Intravesical Ozone Gas in Interstitial Cystitis /Bladder Pain Syndrome

NCT04789135 | Unknown Phase 2 DMC

• 1 other identifier: MVdeAraujoPires
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Interstitial Cystitis / bladder pain syndrome (CI / BPS) is a debilitating pathology with a negative impact on the quality of life of affected individuals. It is characterized as the sensation of pain or discomfort related to the urinary bladder, accompanied by symptoms of the lower urinary tract, in the absence of infection. Among the phenotypes are Cystitis with Hunner's ulcer, essentially inflammatory pathology and without Hunner's lesion, non-inflammatory frequently associated with somatoform systemic changes. Functional changes in urothelium and epithelial barrier, neurogenic inflammation and autoimmune mechanisms are involved in the development of the disease. Medical ozone has anti-inflammatory, antioxidant, cytoprotective, antimicrobial and immunomodulatory properties. When administered, it is dissolved in biological fluids, immediately reacting with glycoproteins composed of carbohydrates and polypeptide chains. This reaction results in the formation of hydrogen peroxide (H2O2), lipid oxidation products (LOS), increased activation of erythroid-related nuclear transcription factors (Nrf2) activation of antioxidant response transcription elements (ARE) and increased variety of antioxidant enzymes that act as free radical scavengers. Benefits of O3 have been demonstrated in the treatment of neuropathic pain and hyperalgesia associated with the analgesic and anti-inflammatory effect. The objective of this work is to evaluate the effect of intravesical ozone gas administration in patients with Interstitial Cystitis / Painful Bladder Syndrome with low response to conventional therapy.

Conditions

Interstitial Cystitis, Chronic; Bladder Pain Syndrome

Keywords

Interstitial cystitis; Bladder pain Sydrome; Ozone therapy

Outcome Measures

Primary Outcomes (1)

• Evaluation of the response to the use of intravesical medicinal ozone gas in patients with Interstitial Cystitis / Bladder Pain Syndrome (IC / BPS) using the O'Leary Sant Symptom and Problem Index questionnaire

  The O 'Leary Sant Symptom and Problem Index is validated as a self-report measure of urinary symptoms and pain and how problematic these symptoms are for individuals with IC / BPS. The measure assesses symptoms and problems of IC / BPS through four questions, generating a symptom score (ICSI), problem score (ICPI) and total severity score. Symptom scores (ICSI) range from 0 to 21 and problem scores from 0 to 16, with a combined total score of 0 to 37. ICSI and ICPI score values greater than 6 alone are considered severe symptoms. Symptom scores (ICSI) greater than 5 have 94% sensitivity and 50% specificity for the diagnosis of patients with IC / BPS. At the end of the study, the symptom score cut-off point (ICSI) below 5 will be considered as a therapeutic response measure. The problem scores will be assessed through an improvement percentage, with values greater than 75% being considered as adequacy.

  The O'Leary Sant Symptom and Problem Index questionnaire will be applied upon admission, after the third and sixth application of intravesical. Follow-up will be carried out monthly thereafter until the sixth month of the intervention as a response check

Study Arms (1)

Ozone Therapy

EXPERIMENTAL

Administration of intravesical ozone gas in patients with Interstitial cystitis/bladder pain sydrome

Drug: Ozone

Interventions

Ozone DRUG

Treatment consists of direct instillation into the bladder of ozone gas, with concentration of 20µg / ml - 60ml via urethral catheter.

Also known as: Ozone Therapy, Intravesical medications

Ozone Therapy

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Interstitial Cystitis
• Bladder pain Syndrome

You may not qualify if:

• Malignant Neoplasm
• Bladder Lithiasis.
• Lower Tract Infections

Sponsors & Collaborators

• Anhembi Morumbi University: lead

Study Sites (1)

Distal Nefrologia e Urologia

Jacareí, São Paulo, 12327-300, Brazil

Location

Related Publications (20)

• Akiyama Y, Luo Y, Hanno PM, Maeda D, Homma Y. Interstitial cystitis/bladder pain syndrome: The evolving landscape, animal models and future perspectives. Int J Urol. 2020 Jun;27(6):491-503. doi: 10.1111/iju.14229. Epub 2020 Apr 4.

  PMID: 32246572 BACKGROUND

• Grover S, Srivastava A, Lee R, Tewari AK, Te AE. Role of inflammation in bladder function and interstitial cystitis. Ther Adv Urol. 2011 Feb;3(1):19-33. doi: 10.1177/1756287211398255.

  PMID: 21789096 BACKGROUND

• Akiyama Y, Hanno P. Phenotyping of interstitial cystitis/bladder pain syndrome. Int J Urol. 2019 Jun;26 Suppl 1:17-19. doi: 10.1111/iju.13969.

  PMID: 31144756 BACKGROUND

• Birder LA. Pathophysiology of interstitial cystitis. Int J Urol. 2019 Jun;26 Suppl 1:12-15. doi: 10.1111/iju.13985.

  PMID: 31144735 BACKGROUND

• Quaghebeur J, Wyndaele JJ. Bladder pain syndrome (BPS): Symptom differences between type 3C BPS and non-type 3C BPS. Scand J Urol. 2015;49(4):319-20. doi: 10.3109/21681805.2014.982170. Epub 2014 Nov 27. No abstract available.

  PMID: 25428753 BACKGROUND

• Han E, Nguyen L, Sirls L, Peters K. Current best practice management of interstitial cystitis/bladder pain syndrome. Ther Adv Urol. 2018 Mar 19;10(7):197-211. doi: 10.1177/1756287218761574. eCollection 2018 Jul.

  PMID: 30034539 BACKGROUND

• Arance I, Ramon de Fata F, Angulo JC, Gonzalez-Enguita C, Errando C, Cozar JM, Esteban M. [Available evidence about efficacy of different restoring agents of glycosaminoglycans for intravesical use in interstitial cystitis]. Actas Urol Esp. 2013 Feb;37(2):92-9. doi: 10.1016/j.acuro.2012.10.002. Epub 2012 Dec 20. Spanish.

  PMID: 23260184 BACKGROUND

• Patnaik SS, Lagana AS, Vitale SG, Buttice S, Noventa M, Gizzo S, Valenti G, Rapisarda AMC, La Rosa VL, Magno C, Triolo O, Dandolu V. Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome. Arch Gynecol Obstet. 2017 Jun;295(6):1341-1359. doi: 10.1007/s00404-017-4364-2. Epub 2017 Apr 8.

  PMID: 28391486 BACKGROUND

• Sagai M, Bocci V. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress? Med Gas Res. 2011 Dec 20;1:29. doi: 10.1186/2045-9912-1-29.

  PMID: 22185664 BACKGROUND

• Smith NL, Wilson AL, Gandhi J, Vatsia S, Khan SA. Ozone therapy: an overview of pharmacodynamics, current research, and clinical utility. Med Gas Res. 2017 Oct 17;7(3):212-219. doi: 10.4103/2045-9912.215752. eCollection 2017 Jul-Sep.

  PMID: 29152215 BACKGROUND

• Di Mauro R, Cantarella G, Bernardini R, Di Rosa M, Barbagallo I, Distefano A, Longhitano L, Vicario N, Nicolosi D, Lazzarino G, Tibullo D, Gulino ME, Spampinato M, Avola R, Li Volti G. The Biochemical and Pharmacological Properties of Ozone: The Smell of Protection in Acute and Chronic Diseases. Int J Mol Sci. 2019 Feb 1;20(3):634. doi: 10.3390/ijms20030634.

  PMID: 30717203 BACKGROUND

• Fuccio C, Luongo C, Capodanno P, Giordano C, Scafuro MA, Siniscalco D, Lettieri B, Rossi F, Maione S, Berrino L. A single subcutaneous injection of ozone prevents allodynia and decreases the over-expression of pro-inflammatory caspases in the orbito-frontal cortex of neuropathic mice. Eur J Pharmacol. 2009 Jan 28;603(1-3):42-9. doi: 10.1016/j.ejphar.2008.11.060. Epub 2008 Dec 6.

  PMID: 19100257 BACKGROUND

• Wei A, Feng H, Jia XM, Tang H, Liao YY, Li BR. Ozone therapy ameliorates inflammation and endometrial injury in rats with pelvic inflammatory disease. Biomed Pharmacother. 2018 Nov;107:1418-1425. doi: 10.1016/j.biopha.2018.07.137. Epub 2018 Sep 1.

  PMID: 30257358 BACKGROUND

• Elvis AM, Ekta JS. Ozone therapy: A clinical review. J Nat Sci Biol Med. 2011 Jan;2(1):66-70. doi: 10.4103/0976-9668.82319.

  PMID: 22470237 BACKGROUND

• Hernandez FA. To what extent does ozone therapy need a real biochemical control system? Assessment and importance of oxidative stress. Arch Med Res. 2007 Jul;38(5):571-8. doi: 10.1016/j.arcmed.2007.03.002.

  PMID: 17560465 BACKGROUND

• Uguz S, Demirer Z, Uysal B, Alp BF, Malkoc E, Guragac A, Turker T, Ates F, Karademir K, Ozcan A, Yildirim I, Korkmaz A, Guven A. Medical ozone therapy reduces shock wave therapy-induced renal injury. Ren Fail. 2016 Jul;38(6):974-81. doi: 10.3109/0886022X.2016.1172941. Epub 2016 Apr 20.

  PMID: 27099130 BACKGROUND

• 19. Renate Viebahn-Hänsler , Olga Sonia León Fernández & Ziad Fahmy (2012) Ozone in Medicine: The Low- Dose Ozone Concept-Guidelines and Treatment Strategies, Ozone: Science & Engineering: The Journal of the International Ozone Association, 34:6, 408-424, DOI: 10.1080/01919512.2012.717847

  BACKGROUND

• McKernan LC, Bonnet KR, Finn MTM, Williams DA, Bruehl S, Reynolds WS, Clauw D, Dmochowski RR, Schlundt DG, Crofford LJ. Qualitative Analysis of Treatment Needs in Interstitial Cystitis/Bladder Pain Syndrome: Implications for Intervention. Can J Pain. 2020;4(1):181-198. doi: 10.1080/24740527.2020.1785854. Epub 2020 Sep 1.

  PMID: 33367196 BACKGROUND

• Malde S, Palmisani S, Al-Kaisy A, Sahai A. Guideline of guidelines: bladder pain syndrome. BJU Int. 2018 Nov;122(5):729-743. doi: 10.1111/bju.14399. Epub 2018 Jun 13.

  PMID: 29777618 RESULT

• Cox A, Golda N, Nadeau G, Curtis Nickel J, Carr L, Corcos J, Teichman J. CUA guideline: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Can Urol Assoc J. 2016 May-Jun;10(5-6):E136-E155. doi: 10.5489/cuaj.3786. Epub 2016 May 12. No abstract available.

  PMID: 27790294 RESULT

MeSH Terms

Conditions

Cystitis, Interstitial

Interventions

Ozone

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)

Oxygen; Gases; Inorganic Chemicals

Study Officials

• Maria Pires, Pires

  Anhembi Morumbi University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Master's Student

Model Details: Experimental. Nature of descriptive analysis of the exploratory type, as it seeks to gather characteristics and information about the studied phenomena

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 9, 2021
• Study Start: March 20, 2020
• Primary Completion: September 30, 2020
• Study Completion: March 1, 2021
• Last Updated: March 9, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be shared within a maximum period of six months from the date of publication of the trial

Locations

BR (1)