Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Multicenter Clinical Trial to Evaluate the Efficacy of Amitriptyline for the Treatment of Painful Bladder Syndrome (PBS) in Newly Diagnosed Patients
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.


Options:
A: Inclusion Criteria:

* Patients with IC/PBS who have failed conventional treatments for at least 6 months will be enrolled.
* A diagnosis of IC/PBS has been established based on characteristic symptoms and cystoscopic findings of glomerulations, petechia, or mucosal fissures after hydrodistention.
* All patients have been treated with at least two types of treatment modalities including non-steroid anti-inflammatory drugs, oral pentosan polysulfate sodium (PPS), intravesical instillation of heparin, hyaluronic acid, or tricyclic antidepressant for at least 6 months but the symptoms remained unchanged or relapsed.

Exclusion Criteria:

* Exclusion criteria proposed by NIDDK
* Automatic exclusions:

  1. Age \<18 years old
  2. Benign or malignant bladder tumors
  3. Radiation cystitis Tuberculous cystitis
  4. Bacterial cystitis
  5. Vaginitis
  6. Cyclophosphamide cystitis
  7. Symptomatic urethral diverticulum
  8. Uterine, cervical, vaginal, or urethral cancer
  9. Active herpes
  10. Bladder or lower ureteral calculi
  11. Waking frequency \<5 times in 12 hours
  12. Nocturia \<2 times
  13. Symptoms relieved by antibiotics, urinary antiseptics, urinary analgesics (for example phenazopyridine hydrochloride)
  14. Duration \< 12 months
  15. Involuntary bladder contractions (urodynamics)
  16. Capacity \> 400ml, absence of sensory urgency
* Automatic inclusions:

  1.Hunner's ulcer
* Positive factors: (two positive factors are necessary for inclusion)

  1. Pain on bladder filling relieved by emptying
  2. Pain (suprapubic, pelvic, urethral, vaginal or peripheral)
  3. Glomerulations on endoscopy
  4. Decreased compliance on cystometrogram
  5. Bladder distention is defined arbitrarily as 80 cm water pressure for 1 minute
* Use of Anticholinergic drugs, for the treatment of lower urinary tract symptoms who have an effect.
* Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up.
* Patients with bladder outlet obstruction on enrollment.
* Patients with urinary retention, PVR≥150 ml.
* Patients with uncontrolled confirmed diagnosis of acute urinary tract infection.
* Patients have laboratory abnormalities at screening including:

  1. Alanine aminotransferase (ALT) \> 3 x upper limit of normal range
  2. Aspartate aminotransferase (AST) \> 3 x upper limit of normal range.
  3. Patients have abnormal serum creatinine level \> 2 x upper limit of normal range.
* Can not be used in the treatment of patients with transurethral catheter treatment.
* Pregnant and lactating women or women who intend to become pregnant during the study or have myasthenia gravis, Eaton Lambert syndrome.
* Patients with any other serious disease or condition considered by the investigator not suitable for entry into the trial.
* Patients participated investigational drug trial within 1 month before entering this study.
* Written informed consent has been obtained.
* Patient who did not complete the 3-day micturition diary according to the instruction.
* Intestinal bladder augmentation patients receive angioplasty for the treatment of overactive bladder.
B: 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
C: Inclusion Criteria:

1. A diagnosis of IC/BPS defined based on AUA guidelines as the following: an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 months duration, in the absence of infection or identifiable causes, documented history or patient reported.
2. Only those patients with moderate to severe IC/BPS will be included in the study.
3. Able to provide informed consent to participate in the study and comply with study requirements
4. Able to provide written authorization for use and release of health and research study information
5. Written documentation of being provided California's Experimental Subject's Bill of Rights
6. Females ≥18 and ≤ 65 years of age previously diagnosed with interstitial cystitis/ bladder pain syndrome (IC/BPS) for a duration of greater than 6 months
7. Female patients of child-bearing potential must have a negative serum pregnancy test at Screening and use birth control while in the study.
8. O'Leary-Sant Interstitial Cystitis Symptom and Problem Indexes (OSPI) score ≥ 18
9. No history of any cancer.
10. No bacterial cystitis in previous 1 month
11. No active herpes in previous 3 months
12. Never treated with cyclophosphamide
13. No neurogenic bladder dysfunction (due to a spinal cord injury, stroke, Parkinson's disease, multiple sclerosis, spina bifida or diabetic cystopathy)
14. Absence of bladder, ureteral or urethral calculi for previous 3 months

Exclusion criteria:

1. Symptoms are relieved at one month reevaluation visit after receiving IC/BPS behavior modification advice at screening visit.
2. Symptoms are relieved by antimicrobials, antibiotics, or other medications for IC/BPS
3. Pregnant women, lactating mothers, nursing mothers, women suspected of being pregnant and woman who plan to be pregnant during the course of the clinical trial
4. Males
5. Patients with inadequate renal, hepatic, or cardiac function
6. Patients with history of gross hematuria within 2 years.
7. Patients with the following medical history: Lower urinary tract anatomical anomaly, pelvic radiotherapy, or active genital herpes
8. Patients with a history of tuberculosis (TB), recent exposure to TB, or recent travel to TB endemic regions. Patients should have a recent negative PPD (or negative CXR) prior to receiving treatment.
9. Patients who have undergone cystoscopy under anesthesia with bladder biopsy, hydrodistension, or fulguration of Hunner's ulcer within 3 months
10. Patients taking the following treatments for interstitial cystitis at Screening: Intravesical BCG, corticosteroid therapy, cyclosporine, or TNF-alpha inhibitors.
11. Patients with a history of receiving live vaccine including Flumist® influenza vaccine in the past 3 months.
12. Patients with a history of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
13. Patients with a history of alcohol, analgesic or drug abuse within 2 years of Screening.
14. Patients with a history of any cancer.
15. Patients with a history of active Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) infection, or who are known carriers (Hepatitis B).
16. Patients with a history of invasive fungal infections, recent travel to regions endemic for the following invasive fungal infections: San Joaquin Fever, aspergillosis, histoplasmosis, candidiasis, coccidiodomycosis, blastomycosis, and pneumocystosis.
17. Patients with a history of diabetes mellitus.
18. Patients with a history of a neurologic disease included but not limited to central demyelinating diseases, including multiple sclerosis; and a history of peripheral demyelinating disease, including Guillain-Barre syndrome.
19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
D: Inclusion Criteria:

* Women 18 years and older
* Women with IC/BPS who have a score of ≥ 6 on either index (problem or symptom index) of the O'Leary-Sant questionnaire who have selected bladder instillations as part of their IC/BPS treatment
* Suitability for follow-up

Exclusion Criteria:

* Contraindications and/or allergies to the ingredients used in the bladder instillations
* Diagnosis of idiopathic thrombocytopenic purpura
* Does not desire to undergo bladder instillation therapy or unwilling to undergo bladder instillation therapy on schedule mandated by study
* Have a known alternative diagnosis explaining bladder pain symptoms that would preclude the diagnosis of IC/BPS (e.g. radiation cystitis, active urinary tract infection with bacteria or fungus treated within last 2 weeks or diagnosed at index visit, bladder injury or trauma within the last 30 days)
* Inability to speak or read English
* Bladder instillation within the past 4 weeks

Answer: B