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

Sponsor

University Hospital Inselspital, Berne (Other)

Overall Status

Terminated

CT.gov ID

NCT01879930

Collaborator

(none)

Enrollment

Location

Arms

27.9

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Pelvic Pain Syndrome Bladder Pain Syndrome	Drug: doxycycline Drug: placebo	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in the O'Leary-Sant IC symptom and problem index total score from baseline [4, 8 , 24 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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