Bladder DiseasesPhase 3IC01NCT00124306
Efficacy of Amitriptyline for Painful Bladder Syndrome (PBS)
A Phase 3 study testing Amitriptyline in people with Bladder Diseases and Interstitial Cystitis, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 10 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Bladder Diseases, Interstitial Cystitis
- What is being tested?
- Amitriptyline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 271 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Feb 2005to Dec 2008
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
University of Maryland
Baltimore, Maryland, 21201
Henry Ford Hospital
Detroit, Michigan, 48202
University of Iowa Hospitals and Clinic
Iowa City, Iowa, 52242
Loyola University Medical Center
Maywood, Illinois, 60153
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Rochester Medical Center
Rochester, New York, 14642
William Beaumont Hospital
Royal Oak, Michigan, 48073
University of Washington
Seattle, Washington, 98195
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: 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.
Read the 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.
- Conditions
- Bladder Diseases, Interstitial Cystitis
- Being tested
- Amitriptyline, Placebo
- Keywords
- painful bladder syndrome, interstitial cystitis, newly diagnosed
- Medical subject headings
- Urinary Bladder Diseases, Cystitis, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmitriptylineDrug
Also called Elavil
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.
PlaceboOther
Placebo will be dosed exactly as active arm.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 Weeks
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2005 (estimated)
- Study startFeb 2005
- Primary completionApr 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bladder DiseasesStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 271 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- University of Pennsylvania
- Responsible party
- Sponsor
- Investigators
- Leroy M. Nyberg, Jr., Ph.D, M.D., Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00124306
- Sponsor's protocol ID
- ICCRN RCT1 - Amitriptyline
- Other IDs
- U01DK065209
- Acronym
- IC01
- Status last verified
- Aug 2025
- First submitted
- 13 Jul 2005
- Last updated
- 12 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 20303115Imamura 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.
PubMed 32734597