Assessment of Potential Biomarkers in Women With Symptoms of Overactive Bladder and Pelvic Organ Prolapse

NCT03516292 | Unknown

• 1 other identifier: 411/29.03.2018
• Study Type: observational
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to investigate the role of certain biomarkers in the initial assessment of women with overactive bladder (OAB). Nerve Growth Factor (NGF) levels, measured in urine samples, and bladder wall thickness (BWT), determined by two-dimensional transvaginal ultrasound, are two of those markers. The investigators hypothesize that the pre-operative determination of these biomarkers in women suffering from genital prolapse and overactive bladder could lead to a more accurate prognosis of the post-operative course of overactive bladder symptoms in women undergoing surgical treatment of prolapse.

Conditions

Overactive Bladder

Keywords

overactive bladder; biomarker; nerve growth factor; vaginal prolapse; urinary incontinence

Outcome Measures

Primary Outcomes (2)

• Urinary NGF as a biomarker for OAB symptoms in women with POP

  Determination of urinary NGF levels' change as a reliable prognostic factor for the treatment of OAB in women with POP before and after surgical repair

  Two samples will be taken at the time of recruitment (Month 0) at three months post-operatively (Month 3).

• Urinary NGF as a biomarker for OAB symptoms in women with POP

  Determination of urinary NGF levels' change as a reliable prognostic factor for the treatment of OAB in women with POP before and after surgical repair.

  Two samples will be taken at the time of recruitment (Month 0) and at the 1 years follow up appointment post-operatively (Month 12)

Secondary Outcomes (1)

• BWT as a biomarker for OAB symptoms in women with POP

  Ultrasound will take place before surgery repair (Month 0) at three months post-operatively (Month 3).

Study Arms (2)

OAB-POP group

As an Observational Case-Control Study, the participants will divided in two groups depending whether they suffer from overactive bladder symptoms or not. All participants will have POP.

Diagnostic Test: Urinary Nerve Growth Factor

POP only group

As an Observational Case-Control Study, the participants will divided in two groups depending whether they suffer from overactive bladder symptoms or not. All participants will have POP.

Diagnostic Test: Urinary Nerve Growth Factor

Interventions

Urinary Nerve Growth Factor DIAGNOSTIC_TEST

The subjective patient's discomfort regarding the vaginal prolapse problems and urinary incontinency symptoms will be assessed through the following questionnaires: (a) ICIQ-OAB (b) ICIQ FLUTS (c) ICIQ-VS. Determination of the bladder neck of urethra in midsagittal plane using a transvaginal two-dimensional ultrasound machine at lithotomy position in rest (point OA) and on Valsalva maneuver (point OB). Bladder Neck Mobility is defined as the difference from point OA to OB. BWT is determined and measured as the hypoechoic layer between two hyperechoic layers that is recognized as the urothelium and the perivesical tissue using a transvaginal two-dimensional ultrasound machine at lithotomy position. The measurement is performed with a bladder volume \<30 ml and is taken place in 3 different bladder sites: (a) the thickest part of the bladder triangle, (b) the dome of the bladder in the midline, (c) the anterior wall of the bladder. NGF will be measured in urine sample.

Also known as: Bladder Wall Thickness, Bladder Neck Mobility, Clinical Assessment of Subjective Vaginal and Urinary Symptoms

OAB-POP group; POP only group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women that visited outpatients Gynecology Department, 1st Department Obstetrics and Gynecology, Aristotle University of Thessaloniki, General Hospital Papageorgiou of Thessaloniki, complaining for vaginal prolapse and possible concomitant urinary problems.

You may qualify if:

• Adult women that are able to communicate and understand comprehensively Greek Language and present vaginal prolapse problems.

You may not qualify if:

• Male patients as well children will be excluded.
• Women that have already operated once for pelvic organ prolapse.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (1)

Aristotle University of Thessaloniki

Thessaloniki, Central Macedonia, 54124, Greece

RECRUITING

Related Publications (43)

• de Boer TA, Salvatore S, Cardozo L, Chapple C, Kelleher C, van Kerrebroeck P, Kirby MG, Koelbl H, Espuna-Pons M, Milsom I, Tubaro A, Wagg A, Vierhout ME. Pelvic organ prolapse and overactive bladder. Neurourol Urodyn. 2010;29(1):30-9. doi: 10.1002/nau.20858.

  PMID: 20025017 BACKGROUND

• de Boer TA, Kluivers KB, Withagen MI, Milani AL, Vierhout ME. Predictive factors for overactive bladder symptoms after pelvic organ prolapse surgery. Int Urogynecol J. 2010 Sep;21(9):1143-9. doi: 10.1007/s00192-010-1152-y. Epub 2010 Apr 24.

  PMID: 20419366 BACKGROUND

• Rachaneni S, McCooty S, Middleton LJ, Parker VL, Daniels JP, Coomarasamy A, Verghese TS, Balogun M, Goranitis I, Barton P, Roberts TE, Deeks JJ, Latthe P; Bladder Ultrasound Study (BUS) Collaborative Group. Bladder ultrasonography for diagnosing detrusor overactivity: test accuracy study and economic evaluation. Health Technol Assess. 2016 Jan;20(7):1-150. doi: 10.3310/hta20070.

  PMID: 26806032 BACKGROUND

• Seth JH, Sahai A, Khan MS, van der Aa F, de Ridder D, Panicker JN, Dasgupta P, Fowler CJ. Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)? BJU Int. 2013 Mar;111(3):372-80. doi: 10.1111/j.1464-410X.2012.11672.x.

  PMID: 23444927 BACKGROUND

• Wu JM, Matthews CA, Conover MM, Pate V, Jonsson Funk M. Lifetime risk of stress urinary incontinence or pelvic organ prolapse surgery. Obstet Gynecol. 2014 Jun;123(6):1201-1206. doi: 10.1097/AOG.0000000000000286.

  PMID: 24807341 BACKGROUND

• Forde JC, Davila JL, Marks BK, Epstein M, Tsui JF, Weiss JP, Blaivas JG. Urogynecological conditions associated with overactive bladder symptoms in women. Can Urol Assoc J. 2017 Mar-Apr;11(3-4):E83-E87. doi: 10.5489/cuaj.3962. Epub 2017 Mar 16.

  PMID: 28360952 BACKGROUND

• Eapen RS, Radomski SB. Review of the epidemiology of overactive bladder. Res Rep Urol. 2016 Jun 6;8:71-6. doi: 10.2147/RRU.S102441. eCollection 2016.

  PMID: 27350947 BACKGROUND

• Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN; International Urogynecological Association; International Continence Society. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4-20. doi: 10.1002/nau.20798.

  PMID: 19941278 BACKGROUND

• Bureau M, Carlson KV. Pelvic organ prolapse: A primer for urologists. Can Urol Assoc J. 2017 Jun;11(6Suppl2):S125-S130. doi: 10.5489/cuaj.4634.

  PMID: 28616110 BACKGROUND

• Osman T. Stress incontinence surgery for patients presenting with mixed incontinence and a normal cystometrogram. BJU Int. 2003 Dec;92(9):964-8. doi: 10.1111/j.1464-410x.2003.04519.x.

  PMID: 14632856 BACKGROUND

• Olivera CK, Meriwether K, El-Nashar S, Grimes CL, Chen CC, Orejuela F, Antosh D, Gleason J, Kim-Fine S, Wheeler T, McFadden B, Balk EM, Murphy M; Systematic Review Group for the Society of Gynecological Surgeons. Nonantimuscarinic treatment for overactive bladder: a systematic review. Am J Obstet Gynecol. 2016 Jul;215(1):34-57. doi: 10.1016/j.ajog.2016.01.156. Epub 2016 Feb 4.

  PMID: 26851599 BACKGROUND

• Zargham M, Alizadeh F, Moayednia A, Haghdani S, Nouri-Mahdavi K. The role of pelvic organs prolapse in the etiology of urinary incontinence in women. Adv Biomed Res. 2013 Mar 6;2:22. doi: 10.4103/2277-9175.108010. eCollection 2013.

  PMID: 23977650 BACKGROUND

• Long CY, Hsu SC, Sun DJ, Chen CC, Tsai EM, Su JH. Abnormal clinical and urodynamic findings in women with severe genitourinary prolapse. Kaohsiung J Med Sci. 2002 Dec;18(12):593-7.

  PMID: 12670034 BACKGROUND

• Rosenzweig BA, Pushkin S, Blumenfeld D, Bhatia NN. Prevalence of abnormal urodynamic test results in continent women with severe genitourinary prolapse. Obstet Gynecol. 1992 Apr;79(4):539-42.

  PMID: 1553172 BACKGROUND

• Coates KW, Harris RL, Cundiff GW, Bump RC. Uroflowmetry in women with urinary incontinence and pelvic organ prolapse. Br J Urol. 1997 Aug;80(2):217-21. doi: 10.1046/j.1464-410x.1997.00246.x.

  PMID: 9284191 BACKGROUND

• Basu M, Duckett J. Effect of prolapse repair on voiding and the relationship to overactive bladder and detrusor overactivity. Int Urogynecol J Pelvic Floor Dysfunct. 2009 May;20(5):499-504. doi: 10.1007/s00192-009-0807-z. Epub 2009 Feb 12.

  PMID: 19214362 BACKGROUND

• Salvatore S, Serati M, Ghezzi F, Uccella S, Cromi A, Bolis P. Efficacy of tolterodine in women with detrusor overactivity and anterior vaginal wall prolapse: is it the same? BJOG. 2007 Nov;114(11):1436-8. doi: 10.1111/j.1471-0528.2007.01399.x. Epub 2007 Sep 17.

  PMID: 17877779 BACKGROUND

• Azadzoi KM, Pontari M, Vlachiotis J, Siroky MB. Canine bladder blood flow and oxygenation: changes induced by filling, contraction and outlet obstruction. J Urol. 1996 Apr;155(4):1459-65. doi: 10.1016/s0022-5347(01)66307-9.

  PMID: 8632611 BACKGROUND

• Gosling JA, Gilpin SA, Dixon JS, Gilpin CJ. Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction. J Urol. 1986 Aug;136(2):501-4. doi: 10.1016/s0022-5347(17)44930-5.

  PMID: 3735523 BACKGROUND

• van Koeveringe GA, Mostwin JL, van Mastrigt R, van Koeveringe BJ. Effect of partial urethral obstruction on force development of the guinea pig bladder. Neurourol Urodyn. 1993;12(6):555-66; discussion 566-71. doi: 10.1002/nau.1930120607.

  PMID: 8312940 BACKGROUND

• Steers WD, Kolbeck S, Creedon D, Tuttle JB. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest. 1991 Nov;88(5):1709-15. doi: 10.1172/JCI115488.

  PMID: 1939656 BACKGROUND

• Steers WD, Ciambotti J, Etzel B, Erdman S, de Groat WC. Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction. J Comp Neurol. 1991 Aug 15;310(3):401-10. doi: 10.1002/cne.903100309.

  PMID: 1723990 BACKGROUND

• Ferguson DR, Kennedy I, Burton TJ. ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes--a possible sensory mechanism? J Physiol. 1997 Dec 1;505 ( Pt 2)(Pt 2):503-11. doi: 10.1111/j.1469-7793.1997.503bb.x.

  PMID: 9423189 BACKGROUND

• Yoshida M, Masunaga K, Satoji Y, Maeda Y, Nagata T, Inadome A. Basic and clinical aspects of non-neuronal acetylcholine: expression of non-neuronal acetylcholine in urothelium and its clinical significance. J Pharmacol Sci. 2008 Feb;106(2):193-8. doi: 10.1254/jphs.fm0070115. Epub 2008 Feb 16.

  PMID: 18285653 BACKGROUND

• Jung SY, Fraser MO, Ozawa H, Yokoyama O, Yoshiyama M, De Groat WC, Chancellor MB. Urethral afferent nerve activity affects the micturition reflex; implication for the relationship between stress incontinence and detrusor instability. J Urol. 1999 Jul;162(1):204-12. doi: 10.1097/00005392-199907000-00069.

  PMID: 10379788 BACKGROUND

• Serati M, Salvatore S, Cattoni E, Soligo M, Cromi A, Ghezzi F. Ultrasound measurement of bladder wall thickness in different forms of detrusor overactivity. Int Urogynecol J. 2010 Nov;21(11):1405-11. doi: 10.1007/s00192-010-1194-1. Epub 2010 Jun 10.

  PMID: 20535449 BACKGROUND

• Panayi DC, Tekkis P, Fernando R, Khullar V. Is the beneficial effect of antimuscarinics related to motor or sensory changes in the bladder? Int Urogynecol J. 2010 Jul;21(7):841-5. doi: 10.1007/s00192-010-1123-3. Epub 2010 Mar 27.

  PMID: 20349178 BACKGROUND

• Cruz F, Heesakkers J, Khullar V, Tubaro A. Bladder Wall Thickness in Overactive Bladder: Does It Have a Role? Eur Urol Suppl. 2009; 8(9):769-71

  BACKGROUND

• Antunes-Lopes T, Cruz CD, Cruz F, Sievert KD. Biomarkers in lower urinary tract symptoms/overactive bladder: a critical overview. Curr Opin Urol. 2014 Jul;24(4):352-7. doi: 10.1097/MOU.0000000000000064.

  PMID: 24841379 BACKGROUND

• Schaefer W. Comment on Kuo: Measurement of detrusor wall thickness in women with overactive bladder by transvaginal and transabdominal sonography. Int Urogynecol J. 2010 Jan;21(1):129-30; author reply 131-2. doi: 10.1007/s00192-009-0999-2. Epub 2009 Sep 29. No abstract available.

  PMID: 19787280 BACKGROUND

• Blatt AH, Titus J, Chan L. Ultrasound measurement of bladder wall thickness in the assessment of voiding dysfunction. J Urol. 2008 Jun;179(6):2275-8; discussion 2278-9. doi: 10.1016/j.juro.2008.01.118. Epub 2008 Apr 18.

  PMID: 18423703 BACKGROUND

• Robinson D, Oelke M, Khullar V, Wijkstra H, Tretter R, Stow B, Compion G, Tubaro A. Bladder wall thickness in women with symptoms of overactive bladder and detrusor overactivity: Results from the randomised, placebo-controlled shrink study. Neurourol Urodyn. 2016 Sep;35(7):819-25. doi: 10.1002/nau.22808. Epub 2015 Jul 21.

  PMID: 26199198 BACKGROUND

• Cruz CD. Neurotrophins in bladder function: what do we know and where do we go from here? Neurourol Urodyn. 2014 Jan;33(1):39-45. doi: 10.1002/nau.22438. Epub 2013 Jun 17.

  PMID: 23775873 BACKGROUND

• Liu HT, Kuo HC. Urinary nerve growth factor level could be a potential biomarker for diagnosis of overactive bladder. J Urol. 2008 Jun;179(6):2270-4. doi: 10.1016/j.juro.2008.01.146. Epub 2008 Apr 18.

  PMID: 18423678 BACKGROUND

• Liu HT, Chancellor MB, Kuo HC. Urinary nerve growth factor levels are elevated in patients with detrusor overactivity and decreased in responders to detrusor botulinum toxin-A injection. Eur Urol. 2009 Oct;56(4):700-6. doi: 10.1016/j.eururo.2008.04.037. Epub 2008 Apr 30.

  PMID: 18472208 BACKGROUND

• Kuo HC, Liu HT, Chancellor MB. Can urinary nerve growth factor be a biomarker for overactive bladder? Rev Urol. 2010 Spring;12(2-3):e69-77.

  PMID: 20811555 BACKGROUND

• Liu HT, Chancellor MB, Kuo HC. Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladder. BJU Int. 2009 Jun;103(12):1668-72. doi: 10.1111/j.1464-410X.2009.08380.x. Epub 2009 Feb 11.

  PMID: 19220267 BACKGROUND

• Bray R, Cartwright R, Cardozo L, Hill S, Guan Z, Khullar V. Tolterodine ER reduced increased bladder wall thickness in women with overactive bladder. A randomized, placebo-controlled, double-blind, parallel group study. Neurourol Urodyn. 2018 Jan;37(1):237-243. doi: 10.1002/nau.23281. Epub 2017 Apr 13.

  PMID: 28407338 BACKGROUND

• Digesu GA, Salvatore S, Chaliha C, Athanasiou S, Milani R, Khullar V. Do overactive bladder symptoms improve after repair of anterior vaginal wall prolapse? Int Urogynecol J Pelvic Floor Dysfunct. 2007 Dec;18(12):1439-43. doi: 10.1007/s00192-007-0375-z. Epub 2007 Apr 11.

  PMID: 17429557 BACKGROUND

• Brubaker L, Cundiff GW, Fine P, Nygaard I, Richter HE, Visco AG, Zyczynski H, Brown MB, Weber AM; Pelvic Floor Disorders Network. Abdominal sacrocolpopexy with Burch colposuspension to reduce urinary stress incontinence. N Engl J Med. 2006 Apr 13;354(15):1557-66. doi: 10.1056/NEJMoa054208.

  PMID: 16611949 BACKGROUND

• Lekskulchai O, Dietz HP. Detrusor wall thickness as a test for detrusor overactivity in women. Ultrasound Obstet Gynecol. 2008 Sep;32(4):535-9. doi: 10.1002/uog.5370.

  PMID: 18634113 BACKGROUND

• Liang CC, Tseng LH, Chang YL, Chang SD. Predictors of persistence of preoperative urgency incontinence in women following pelvic organ prolapse repair. Taiwan J Obstet Gynecol. 2015 Dec;54(6):682-5. doi: 10.1016/j.tjog.2014.08.012.

  PMID: 26700985 BACKGROUND

• Weber AM, Walters MD, Piedmonte MR, Ballard LA. Anterior colporrhaphy: a randomized trial of three surgical techniques. Am J Obstet Gynecol. 2001 Dec;185(6):1299-304; discussion 1304-6. doi: 10.1067/mob.2001.119081.

  PMID: 11744900 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine sample of female patients with POP and POP with OAB

MeSH Terms

Conditions

Urinary Bladder, Overactive; Hereditary Sensory and Autonomic Neuropathies; Uterine Prolapse; Urinary Incontinence

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Pelvic Organ Prolapse; Prolapse; Pathological Conditions, Anatomical; Urination Disorders

Study Officials

• Themistoklis Mikos, MD PhD

  Aristotle University Of Thessaloniki

  STUDY DIRECTOR

Central Study Contacts

Sofia Tsiapakidou, PhDc

CONTACT

6946321158; sofiatsiapakidou@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, PhD Candidate, Resident Doctor in Obstetrics & Gynecology,

Study Record Dates

• First Submitted: April 22, 2018
• First Posted: May 4, 2018
• Study Start: January 29, 2018
• Primary Completion: January 30, 2022
• Study Completion: December 30, 2022
• Last Updated: December 13, 2021

Record last verified: 2021-12

Locations

GR (1)