Efficacy of Amitriptyline for Painful Bladder Syndrome (PBS) (IC01)

A Randomized Multicenter Clinical Trial to Evaluate the Efficacy of Amitriptyline for the Treatment of Painful Bladder Syndrome (PBS) in Newly Diagnosed Patients

This is a randomized clinical trial study to test the efficacy and safety of amitriptyline in the treatment of patients newly diagnosed with painful bladder syndrome (PBS). PBS is defined by symptoms--frequent urination day and night and increasing pain as the bladder fills--according to the International Continence Society. The syndrome includes interstitial cystitis (IC), which has been estimated to affect as many as 700,000 people, mostly women. Estimates for PBS vary widely, but as many as 10 million people may suffer from this condition. Although amitriptyline is a Food and Drug Administration (FDA)-approved medication used for depression, the way it works makes it useful for treating the pain of fibromyalgia, multiple sclerosis, and other chronic pain syndromes. Prior small studies in interstitial cystitis (IC) suggested the drug may be a wise choice for this syndrome as well, because it blocks nerve signals that trigger pain and may also decrease muscle spasms in the bladder, helping to relieve the symptoms of pain and frequent urination.

Study Overview

• Status: Completed
• Conditions: Interstitial Cystitis; Bladder Diseases
• Intervention / Treatment: Drug: Amitriptyline; Other: Placebo

Detailed Description

The current trial is recruiting newly diagnosed adults who have not yet received treatment. Approximately 270 participants will be randomly assigned to take up to 75 milligrams of amitriptyline or a placebo each day for 14 to 26 weeks. All participants will be given techniques to practice suppressing the urge to urinate for increasingly longer stretches until they can wait 3 or 4 hours before going to the bathroom. Participants will also regulate when and how much they drink and avoid bladder irritants such as alcohol, acidic foods and carbonated or caffeinated drinks. Staff and patients will find out who received the amitriptyline when the study is finished. Medications and tests are free to participants.

Ten medical centers in the United States and Canada are recruiting adults newly diagnosed with either painful bladder syndrome (PBS) or interstitial cystitis (IC).The centers make up the Interstitial Cystitis Clinical Research Network, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at NIH.

• Study Type: Interventional
• Enrollment (Actual): 271
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2Y7
      • Queen's University
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant must report bladder pain/discomfort score of 3 or greater on a 0-10 Likert scale over the previous 4 weeks.
• Participant must report a symptom score of abnormal urinary frequency of 3 or greater on a 0-10 Likert scale over the previous 4 weeks.
• Symptoms of abnormal urinary frequency and bladder pain/discomfort must have been present for at least six weeks prior to screening visit.

Exclusion Criteria:

• Known allergy or intolerance to amitriptyline or any of its components.
• Currently receives treatment with amitriptyline or other tricyclic antidepressant, selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), or monoamine oxidase (MAO) inhibitor antidepressants.
• Previous treatment with amitriptyline or other tricyclics, hydroxyzine or other antihistamines for bladder symptoms; pentosanpolysulfate; DMSO or any other intravesical therapy, biofeedback or pelvic floor physical therapy for PBS symptoms

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: 1 - Amitriptyline; Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily for a total of 12 weeks.	Drug: Amitriptyline; Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.; Other Names: Elavil
Placebo Comparator: 2 - Placebo; Placebo will be dosed exactly as the active arm and taken once daily for a total of 12 weeks.	Other: Placebo; Placebo will be dosed exactly as active arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Response Assessment (GRA)	The primary efficacy analysis was based on intent to treat, comparing the proportion of responders between treatment arms on a patient reported GRA recorded at 12 weeks or study withdrawal. The 7-point GRA queried, "As compared to when you started the current study, how would you rate your overall symptoms now?" The 7 response options were markedly worse, moderately worse, slightly worse, the same, slightly improved, moderately improved and markedly improved. Participants who indicated that they were markedly or moderately improved were considered responders. Subjects who withdrew from the study for any reason and did not provide data on the primary outcome were considered treatment failures, and were included in the denominator for calculation of response rates.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Quality of Life Measures From Baseline to 12 Weeks	A number of secondary outcomes [as detailed in the Baseline Measures section] were assessed throughout the study. These outcomes include pain, urgency and frequency on 0 to 10-point Likert scales, a 24-hour voiding diary, the Health Status Questionnaire for Quality of Life (SF-36), the Hospital Anxiety and Depression Scale, and the Female Sexual Function Index or International Index of Erectile Function. When applicable, additional analyses of the symptom outcomes may include evaluation of secondary response rates defined by specific changes in symptoms. Associations between changes from baseline in secondary outcomes and GRA will be used to supplement the primary endpoint analysis, and to evaluate the validity of the symptom scales for assessing change.	Baseline and 12 Weeks
Adherence to Study Drug and Urinary Educational/Behavioral Program (EBMP Educational/Behavioral Modification Program)	Adherence to protocol treatment, to study drug and EBMP, at 6 weeks was assessed in 4 categories of 1) symptom management, 2) fluid management, 3) diet modification and 4) bladder training. For each of these EBMP categories adherence was defined as the overall percentage of participants who reported adhering to each component of the EBMP at each telephone contact or clinic visit. Subjects were classified into 3 groups based on the maximum dose obtained at 6 and 12 weeks as shown in the Outcome Measure Data Table below.	12 weeks
Change in Nighttime Voiding From Baseline to 12 Weeks	Baseline nighttime [sleep period] voiding frequency was collected by participant report on a Voiding Diary with entries for each void in a 24-hour period. Each void entry included the question: "Did this void occur during your intended sleep period?" Responses: 1=Yes, 0=No. The sum was totaled for "Yes" entries in response to this question.	Baseline and 12 weeks
Change in Urinary Symptoms Measures	The O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices, and the University of Wisconsin Interstitial Cystitis Symptom Inventory The IC Symptom Index is a 4-question survey w/ a severity scale from min.0(not at all) to max.5(always). The IC Problem Index is a 4-question survey with a severity scale ranging from min.0 (no problem) to max.4 (big problem). Higher subscale responses for each index indicate more severe symptoms. A sub-set of the University of Wisconsin Symptom Survey is designated as the Interstitial Cystitis Symptom Inventory w/ questions ranging from 0(not at all) to 6(a lot). Pts. reported symptoms the day of assessment. Scores ranged from 0 to 42. A higher score indicates more severe symptoms. Symptoms include: bladder pain; bladder discomfort; getting up at night to go to the bathroom; going to the bathroom frequently during the day; urgency to urinate; difficulty sleeping because of bladder problems; and burning sensation in the bladder.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: University of Pennsylvania
• Investigators: Study Director: Leroy M. Nyberg, Jr., Ph.D, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• 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.
• Foster HE Jr, Hanno PM, Nickel JC, Payne CK, Mayer RD, Burks DA, Yang CC, Chai TC, Kreder KJ, Peters KM, Lukacz ES, FitzGerald MP, Cen L, Landis JR, Propert KJ, Yang W, Kusek JW, Nyberg LM; Interstitial Cystitis Collaborative Research Network. Effect of amitriptyline on symptoms in treatment naive patients with interstitial cystitis/painful bladder syndrome. J Urol. 2010 May;183(5):1853-8. doi: 10.1016/j.juro.2009.12.106. Epub 2010 Mar 29.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: July 13, 2005
• First Submitted That Met QC Criteria: July 26, 2005
• First Posted (Estimated): July 27, 2005

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: newly diagnosed; interstitial cystitis; painful bladder syndrome
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Cystitis; Cystitis, Interstitial; Urinary Bladder Diseases; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Dibenzocycloheptenes; Benzocycloheptenes; Amitriptyline
• Other Study ID Numbers: ICCRN RCT1 - Amitriptyline; U01DK065209 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No