Chronic Bladder Pain Syndrome in Women: Can Doxycycline Help? A Prospective Study

Chronic Bladder Pain Syndrome in Women: Can Doxycycline Help? A Prospective, Randomised,Placebo-controlled, Double-blind Study

Chronic bladder pain syndrome is a chronic disabling disorder characterized by chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom such as persistent urgency or frequency in the absence of an identifiable cause. Chronic bladder pain syndrome severely decreases an individual's quality of life and represents a significant financial burden to those affected by it. Currently, multifactorial pathogenesis is assumed including endocrine-involvement, pelvic floor muscle irregularities, immunologic aspects and chemical causes. Corresponding to the wide spectrum of presumptive triggers, a large number of therapeutic approaches are propagated, however most are associated with limited effectiveness. Thus, treatment of BPS is a challenge and the ideal therapy remains to be elucidated. Microorganisms such as Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma genitalium remains a challenge so that these organisms may well be involved in the pathogenesis of chronic bladder pain syndrome. The investigators hypothesise that doxycycline orally for 4 weeks, including therapy of the sexual partner, can significantly relieve symptoms in women with chronic bladder pain syndrome

Study Overview

• Status: Terminated
• Conditions: Bladder Pain Syndrome; Chronic Pelvic Pain Syndrome
• Intervention / Treatment: Drug: doxycycline; Drug: placebo

Detailed Description

Background

Doxycycline is used to treat bacterial infections. Doxycycline is in a class of medications called tetracycline antibiotics. In addition to the general indications for all members of the tetracycline antibiotics group, doxycycline is frequently used to treat chronic prostatitis and pelvic inflammatory disease. Especially intracellular agents, such as chlamydia, are generally susceptible to doxycycline. Assuming this infection to be responsible for the chronic bladder pain syndrome in women, therapy will be performed in accordance with the authorised indication and dosage.Bacterial cystitis is an exclusion criterion for the diagnosis of chronic bladder pain syndrome. However, the detection of microorganisms such as Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma genitalium remains a challenge so that these organisms may well be involved in the pathogenesis of chronic bladder pain syndrome. This is supported by the findings of our retrospective study1 that doxycycline orally for 4 weeks including therapy of the sexual partner lead to a reduction of symptoms in 71% of women complaining of persistent urgency and frequency, chronic urethral and/or bladder pain. Therefore, doxycycline therapy is sensible, especially considering that there are only a few, costly and often little effective symptomatic other treatment options.

Thus, we aim to investigate the effectiveness of doxycycline in women with chronic bladder pain syndrome in a prospective, randomised, placebo-controlled, double-blind study.

Chronic bladder pain syndrome is a chronic disabling disorder characterized by chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom such as persistent urgency or frequency in the absence of an identifiable cause2. In Europe, prevalence rates in women range from 306 to 450/100'0003,4 - much higher than previously estimated. Thus, chronic bladder pain syndrome is a serious economic problem for every health care system. In addition, chronic bladder pain syndrome severely decreases an individual's quality of life and represents a significant financial burden to those affected by it. Currently, multifactorial pathogenesis is assumed including endocrine-involvement, pelvic floor muscle irregularities, immunologic aspects and chemical causes. Corresponding to the wide spectrum of presumptive triggers, a large number of therapeutic approaches are propagated, however most are associated with limited effectiveness. Thus, treatment of BPS is a challenge and the ideal therapy remains to be elucidated. We hypothesise that doxycycline orally for 4 weeks, including therapy of the sexual partner, can significantly relieve symptoms in women with chronic bladder pain syndrome.

Objective

To proof or reject the effectiveness of doxycycline in treatment of chronic bladder pain syndrome

Methods

This is a prospective, randomised, placebo-controlled double-blind trial. Recruitment of the study participants is performed in the urologic outpatient clinic of University Hospital Inselspital Bern.

The randomisation-list in the institute of pharmacy University Hospital Inselspital Bern will only be accessible to unblinded employees. In case of unblinding an authorized member of the blinded trial team contacts the 24-hours service-number of the pharmacist on-duty in the institute of pharmacy. After disclosure of the patient-number, the pharmacist on-duty performs the unblinding and informs the authorized unblinded trial-member about allocation. Finally unblinding is registered on the randomization list by the pharmacist on-duty.

The unblinded trial-member will record the name of the person who performed unblinding and the date and reason for unblinding in the patient's medical record.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Berne, Switzerland, 3010
    • Dep. of Urology, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Bladder pain / suprapubic pressure or discomfort for >6months
• Urgency/urgency incontinence and/or frequency for >6months
• Written informed consent (including confirmation that the partner will also be treated and that during the treatment period sexual intercourse is only allowed using condoms)

Exclusion Criteria

• age < 18 years
• Tetracycline allergy
• Intake of a tetracycline in the last 3 months
• pregnancy
• breast feeding
• bacterial cystitis in the last 4 weeks
• urethral/vaginal/cervical/uterine and/or rectal cancer
• chemical cystitis
• tuberculous cystitis
• benign or malignant bladder tumors
• Lack of radiologic exclusion of pelvic pathology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: doxycycline; Zadorin-100® (doxycycline), licence number Swissmedic: 43051 Legal holder: Mepha Pharma AG, Aesch/BL	Drug: doxycycline; Zadorin-100® (doxycycline), licence number Swissmedic: 43051 Legal holder: Mepha Pharma AG, Aesch/BL Oral intake during study period (4 weeks) once in the morning and once in the evening The masking of the agents is conducted using bordeaux-coloured, opaque hard-gelatine capsules (size 00) of the French company LGA. The hard-gelatine capsules are each filled with 1 unit Zadorin® 100; Other Names: Zadorin-100® (doxycycline), licence number Swissmedic: 43051
Placebo Comparator: placebo; Placebo Galepharm Composition: lactose monohydrate, ceolus PH 102, croscarmellose sodium, magnesiumstearat, manufacturer: Pharmacy Hotz, 8700 Küsnacht, Switzerland	Drug: placebo; Placebo Galepharm Composition: lactose monohydrate, ceolus PH 102, croscarmellose sodium, magnesiumstearat, manufacturer: Pharmacy Hotz, 8700 Küsnacht, Switzerland Oral intake during study period (4 weeks) once in the morning and once in the evening The masking of the agents is conducted using bordeaux-coloured, opaque hard-gelatine capsules (size 00) of the French company LGA. The hard-gelatine capsules are each filled with 1 unit placebo 100mg in the sham-group; Other Names: Placebo Galepharm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the O'Leary-Sant IC symptom and problem index total score from baseline	4, 8 , 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes of patient reported pain, urgency, frequency, functional bladder capacity documented in 72-hour pain and bladder diary, completed during the 3 days before the particular follow-up visit.	4, 8, 24 weeks
Changes in sexual function assessed by the Female Sexual Function Index (FSFI) at the time of the particular follow-up visit	4, 8, 24 weeks

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Fiona Burkhard, Vice Chair urology dep. Inselspital; Study Chair: Claudia Meissner, MD, Department of Urology, Inselspital Bern

Publications and helpful links

General Publications

• van de Merwe JP, Nordling J, Bouchelouche P, Bouchelouche K, Cervigni M, Daha LK, Elneil S, Fall M, Hohlbrugger G, Irwin P, Mortensen S, van Ophoven A, Osborne JL, Peeker R, Richter B, Riedl C, Sairanen J, Tinzl M, Wyndaele JJ. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol. 2008 Jan;53(1):60-7. doi: 10.1016/j.eururo.2007.09.019. Epub 2007 Sep 20.
• Burkhard FC, Blick N, Hochreiter WW, Studer UE. Urinary urgency and frequency, and chronic urethral and/or pelvic pain in females. Can doxycycline help? J Urol. 2004 Jul;172(1):232-5. doi: 10.1097/01.ju.0000128698.93305.2e.
• Temml C, Wehrberger C, Riedl C, Ponholzer A, Marszalek M, Madersbacher S. Prevalence and correlates for interstitial cystitis symptoms in women participating in a health screening project. Eur Urol. 2007 Mar;51(3):803-8; discussion 809. doi: 10.1016/j.eururo.2006.08.028. Epub 2006 Aug 30.
• Leppilahti M, Tammela TL, Huhtala H, Auvinen A. Prevalence of symptoms related to interstitial cystitis in women: a population based study in Finland. J Urol. 2002 Jul;168(1):139-43.
• O'Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, Spolarich-Kroll J. The interstitial cystitis symptom index and problem index. Urology. 1997 May;49(5A Suppl):58-63. doi: 10.1016/s0090-4295(99)80333-1.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 13, 2013
• First Submitted That Met QC Criteria: June 17, 2013
• First Posted (Estimate): June 18, 2013

Study Record Updates

• Last Update Posted (Estimate): March 5, 2015
• Last Update Submitted That Met QC Criteria: March 4, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: randomized; placebo-controlled; doxycycline; double-blind study
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Pain; Neurologic Manifestations; Disease; Cystitis; Syndrome; Somatoform Disorders; Cystitis, Interstitial; Pelvic Pain; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 075/08; 2148 (Inselspital); 2012DR4157 (Other Identifier: Swissmedic)