A Phase 3 interventional study of Amitriptyline and Placebo in Bladder Diseases and Interstitial Cystitis, sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Completed at 10 sites in 2 countries. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-01-12.
Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Phase 3, Interventional, and Treatment
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.
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.
236 studies on the registry are indexed under Cystitis, Interstitial; 35 are open to participants now.
This study's enrollment of 271 is above the median of 51 across 158 interventional studies indexed under Cystitis, Interstitial.
Browse Cystitis, Interstitial studies →National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is the lead sponsor of 538 studies on the registry; 55 are open to participants now.
Of its 80 completed or terminated interventional studies of FDA-regulated products, 51 (64%) have results posted.
Compared within Cystitis, Interstitial, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Urinary Bladder Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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
Placebo will be dosed exactly as the active arm and taken once daily for a total of 12 weeks.
Other: Placebo
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
Placebo will be dosed exactly as active arm.
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.
Time frame: 12 Weeks
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline and 12 weeks
| Milestone | 1 - Active Comparator | 2 - Placebo Comparator |
|---|---|---|
| Started | 135 | 136 |
| Completed | 112 | 119 |
| Not completed | 23 | 17 |
| Withdrew: Adverse event | 7 | 2 |
| Withdrew: Lost to follow-up | 10 | 6 |
| Withdrew: Lack of efficacy | 3 | 6 |
| Withdrew: Personal constraints | 0 | 2 |
| Withdrew: Use of unacceptable medication | 1 | 0 |
| Withdrew: Abnormal lab result | 0 | 1 |
| Withdrew: Other | 2 | 0 |
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.
| Participants | 1 - Active Comparator | 2 - Placebo Comparator |
|---|---|---|
| Marked/moderate improvement | 74 | 61 |
| Slight improvement, same or worse | 61 | 75 |
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.
| Change in score baseline to 12 weeks | 1 - Active Comparator | 2 - Placebo Comparator |
|---|---|---|
| Pain score | -2.6 ± 2.5 | -2.3 ± 2.4 |
| Urgency | -3.0 ± 2.5 | -2.5 ± 2.6 |
| Frequency | -3.5 ± 2.3 | -2.6 ± 2.5 |
| 24-Hr voiding frequency | -4.4 ± 5.4 | -2.0 ± 3.9 |
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.
| Change in score baseline to 12 weeks | 1 - Active Comparator | 2 - Placebo Comparator |
|---|---|---|
| IC Symptom Index | -4.8 ± 3.7 | -3.3 ± 3.9 |
| IC Problem Index | -5.2 ± 3.9 | -3.9 ± 4.0 |
| Wisconsin Symptom Survey | -13.1 ± 10.2 | -9.3 ± 9.3 |
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.
| Participants | 1 - Active Comparator | 2 - Placebo Comparator |
|---|---|---|
| 50 mg or > achieved/maintained @ 12 wks | 62 | 98 |
| 50 mg or > achieved, reduced < 50 by 12 wks | 27 | 20 |
| 50 mg or greater not achieved | 46 | 18 |
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.
| Change in voiding events | 1 - Active Comparator | 2 - Placebo Comparator |
|---|---|---|
| Change in Nighttime Voiding From Baseline to 12 Weeks | -0.9 ± 2.4 | -0.9 ± 2.4 |
Collected over 12 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 1 - Amitriptyline | 0/135 (0%) | 2/135 (1.5%) | 119/135 (88.1%) |
| 2 - Placebo | 0/136 (0%) | 3/136 (2.2%) | 98/136 (72.1%) |
| Event | 1 - Amitriptyline | 2 - Placebo |
|---|---|---|
| Invasive transitional cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/135 | 0/136 |
| HypothyroidismEndocrine disorders | 1/135 | 0/136 |
| Mass found on chest x-rayRespiratory, thoracic and mediastinal disorders | 0/135 | 1/136 |
| Sudden onset of nausea, abdominal pain, SOB, subscapular pain w/left arm radiationCardiac disorders | 0/135 | 1/136 |
| Diagnosed with prostate cancerRenal and urinary disorders | 0/135 | 1/136 |
| Event | 1 - Amitriptyline | 2 - Placebo |
|---|---|---|
| Constitutional symptomsGeneral disorders | 61/135 | 42/136 |
| GastrointestinalGeneral disorders | 57/135 | 32/136 |
| PainNervous system disorders | 43/135 | 48/136 |
| NeurologicalEar and labyrinth disorders | 45/135 | 29/136 |
| GenitourinaryRenal and urinary disorders | 22/135 | 10/136 |
| PulmonaryRespiratory, thoracic and mediastinal disorders | 15/135 | 13/136 |
| Infection, feverInfections and infestations | 9/135 | 14/136 |
| Dermatology/skinSkin and subcutaneous tissue disorders | 9/135 | 10/136 |
| MusculokeletalMusculoskeletal and connective tissue disorders | 7/135 | 3/136 |
| Ocular, visualEye disorders | 3/135 | 7/136 |
| Age, Continuous(years) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| Mean | 38.0 ± 13.8 | 39.9 ± 14.0 | 39.0 ± 13.9 |
| Sex: Female, Male(Participants) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| Female | 115 | 111 | 226 |
| Male | 20 | 25 | 45 |
| Race (NIH/OMB)(Participants) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 18 | 15 | 33 |
| White | 96 | 104 | 200 |
| More than one race | 21 | 17 | 38 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Participants ever diagnosed with IC/PBS(Participants) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| Count of participants | 62 | 75 | 137 |
| Pain score(units on a scale) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| Mean | 5.8 ± 1.5 | 6.0 ± 1.8 | 5.9 ± 1.7 |
| Urgency score(units on a scale) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| Mean | 6.4 ± 1.8 | 6.4 ± 1.8 | 6.4 ± 1.8 |
| Frequency score(units on a scale) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| Mean | 6.8 ± 1.7 | 6.8 ± 1.8 | 6.8 ± 1.8 |
| 24-Hr voiding frequency(Voiding events) | 1 - Active Comparator | 2 - Placebo Comparator | Total |
|---|---|---|---|
| Mean | 13.9 ± 5.2 | 13.7 ± 5.7 | 13.8 ± 5.5 |
4 further baseline measures are reported on the registry.
The record gives a start of Feb 2005, a primary completion of Apr 2008 and a completion of Dec 2008. It does not say whether these dates are actual or estimated.
Results were first posted in Oct 2025, 17 years 6 months after primary completion.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Amitriptyline
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