Efficacy of Amitriptyline for Painful Bladder Syndrome (PBS)

NCT00124306 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ICCRN RCT1 - AmitriptylineU01DK065209
• Study Type: interventional
• Target: 271
• Locations: 2 countries
• Sites: 10

Brief Summary

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.

Conditions

Bladder Diseases; Interstitial Cystitis

Keywords

painful bladder syndrome; interstitial cystitis; newly diagnosed

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Changes in Quality of Life Measures From Baseline to 12 Weeks

  Baseline and 12 Weeks

• Change in Urinary Symptoms Measures

  Baseline and 12 weeks

• Adherence to Study Drug and Urinary Educational/Behavioral Program (EBMP Educational/Behavioral Modification Program)

  12 weeks

• Change in Nighttime Voiding From Baseline to 12 Weeks

  Baseline and 12 weeks

Study Arms (2)

1 - Amitriptyline

ACTIVE COMPARATOR

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

2 - Placebo

PLACEBO COMPARATOR

Placebo will be dosed exactly as the active arm and taken once daily for a total of 12 weeks.

Other: Placebo

Interventions

Amitriptyline DRUG

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.

Also known as: Elavil

1 - Amitriptyline

Placebo OTHER

Placebo will be dosed exactly as active arm.

2 - Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• University of Pennsylvania: collaborator

Study Sites (10)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa Hospitals and Clinic

Iowa City, Iowa, 52242, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Queen's University

Kingston, Ontario, K7L 2Y7, Canada

Location

Related Publications (2)

• 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.

  PMID: 20303115 RESULT

• 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.

  PMID: 32734597 DERIVED

MeSH Terms

Conditions

Urinary Bladder Diseases; Cystitis, Interstitial

Interventions

Amitriptyline

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cystitis

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: J. Richard Landis, PhD
• Organization: University of Pennsylvania

hultman@upenn.edu

215-5734922

Study Officials

• Leroy M. Nyberg, Jr., Ph.D, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2005
• First Posted: July 27, 2005
• Study Start: February 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: December 1, 2008
• Last Updated: January 12, 2026
• Results First Posted: October 7, 2025

Record last verified: 2025-08

Locations

US (9); CA (1)