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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2008

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.

Intervention(s) in this Clinical Trial

• 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: Placebo
  • Placebo will be dosed exactly as active arm.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Amitryptiline
• Placebo Comparator: 2
  • Placebo will be dosed exactly as active arm.

Primary Measures

• Global Response Assessment (GRA)
  • Time Frame: 12 Weeks
    Safety Issue?: Yes

Secondary Measures

• Quality of life measures
  • Time Frame: 12 Weeks
    Safety Issue?: Yes
• Urinary symptoms measures
  • Time Frame: 12 Weeks
    Safety Issue?: No
• Urinary biomarkers
  • Time Frame: 12 Weeks
    Safety Issue?: No
• Adherence to urinary educational/behavioral program
  • Time Frame: 12 weeks
    Safety Issue?: No
• Adverse events
  • Time Frame: 12 Weeks
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Overall Clinical Trial Officials and Contacts

Leroy M. Nyberg, Jr., Ph.D, M.D. Study Director National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00124306

Study ID Number: ICCRN

ClinicalTrials.gov Identifier: NCT00124306

Health Authority: United States: Food and Drug Administration