IC PaIN Trial: Interstitial Cystitis Pain Improvement With Naltrexone

Phase 4

Terminated

Conditions: Naltrexone
Painful Bladder Syndrome
Low Dose Naltrexone
Low-dose Naltrexone
Interstitial Cystitis
Bladder Pain Syndrome

Interventions: Drug: low-dose naltrexone
Drug: Placebo oral tablet

Registration Number: NCT04313972

Lead Sponsor: Endeavor Health

Brief Summary: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating condition with symptoms of urinary urgency, frequency, nocturia (waking up at night to void), and pain, without evidence of urinary tract infection or other identifiable causes. IC/PBS often coexists with other chronic pain syndromes, such as irritable bowel syndrome, chronic fatigue syndrome, and fibromyalgia.

Several treatments exist for IC/PBS; some are not effective, others are time consuming for patients to receive, some can take weeks to months before they become effective, and many have risks associated with them. Low-dose naltrexone (LDN) has demonstrated improvement of symptoms in conditions associated with IC/PBS. LDN is defined as less than 5mg of naltrexone. Some adverse effects have been reported with LDN, the most common are vivid dreams, nightmares, and insomnia.

The investigators hypothesis LDN will have greater than 30% reduction in symptoms as defined by the Interstitial Cystitis Symptom Index in patients diagnosed with IC/PBS from baseline when compared to placebo. The 30% reduction in pain is a standard outcome measure in the pain literature. This improvement has been seen in prior studies where LDN was used to treat pain syndromes.

This will be a randomized double-blinded placebo-controlled prospective trial. Patients meeting diagnostic criteria for IC/PBS by American Urologic Association (AUA) guidelines will be eligible, and then must then meet all applicable inclusion and exclusion criteria. Study participants will sign a consent, complete several questionnaires, give a blood sample to measure liver function tests, and once at home, complete a 24-hour bladder diary.

Participants will be randomized to receive either placebo or study medication. Participants will be instructed to take one capsule nightly for two weeks, then increase to two capsules nightly for four weeks. They will be given a log to record the date and time they take the medication. All study participants will also receive first-line behavioral therapy for IC/PBS of a bladder diet and bladder drills.

After six weeks, participants will complete a second bladder diary. They will then complete the exit study questionnaires, have a second liver function test, return any unused medication, and meet with their doctor to discuss conventional treatment options for IC/PBS.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 3

Inclusion Criteria

Patients aged eighteen and older
Meet criteria for IC/PBS as defined by the American Urology Association as "an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms or more than six weeks duration, in the absence of infection or other identifiable causes" (8)
Newly diagnosed and treatment naïve for IC/PBS or previously diagnosed with IC/PBS, but who have no received treatment in the past four weeks. Patient who use anti-inflammatory medication on an as needed basis in the four weeks prior to the study will be included.
Have had a cystoscopy in the last 6 months prior to study entry to rule out confounding conditions
English speaking
Working telephone number
Able to provide a blood sample to evaluate liver enzymes
Able to attend research visits

Exclusion Criteria

Patients under the age of 18
Patients with known liver disease, including total bilirubin >1.2, AST (aspartate aminotransferase) > 32, ALT (alanine transaminase) > 54
Patients with known kidney disease
Patients who have thyroid disease and who are taking thyroid replacement medications
Patients with known neurologic disease affecting bladder function
Patients with known bladder or urethral cancer
Patients with bladder, urethral, or ureteral calculi
Patients who have had a positive urine culture or a clinical UTI (Urinary Tract Infection) in the past 6 weeks
Patients who are currently pregnant or breast feeding (15)
Patients who are actively using opioid analgesics
Patients with moderate-severe alcohol use disorder
Patients who are actively using sleep aids
Patients who are regularly using anti-inflammatory medications, such as daily Celebrex for arthritis. Those who use an anti-inflammatory medication on an as needed basis may use the medication prior to enrollment in the study.
Patients who have had a known adverse reaction to naltrexone
Patients who are acutely ill
Patients who are diagnosed with a significant psychological comorbidity that would interfere with study participation (32)
Patients who have had a bladder instillation or had oral medical treatment for IC/PBS in the past four weeks.
Patients diagnosed with other chronic pelvic pain syndromes, such as endometriosis
Patients who are unable to swallow pills/capsules
Patients who have had previous treatment with low-dose naltrexone
Patients who have previously scheduled surgeries or procedure during the study time period that would require analgesia.
Patients who are sexually active and of childbearing potential who are unwilling to use an established and reliable form of contraception for the duration of the study.
Patients who are unwilling to have a serum blood test to assess serum transaminases and serum bilirubin.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-dose naltrexone	low-dose naltrexone	2mg low-dose naltrexone capsules
Placebo	Placebo oral tablet	Placebo capsules

Primary Outcome Measures

Name	Time	Method
Interstitial Cystitis Symptom Index	six weeks	The effect of LDN (low-dose naltrexone) in decreasing symptoms associated with IC/PBS (interstitial cystitis/painful bladder syndrome) when treating with low-dose naltrexone as scored by the Interstitial Cystitis Symptom Index as compared to placebo. Scores are from 0 to 20, with lower scores indicating less symptoms associated with IC/PBS.
Visual Analog Scale	six weeks	The effect of LDN in decreasing pain associated with IC/PBS when treating with low-dose naltrexone as scored by visual analog scale as compared with placebo. Scores are from 0 to 10, with lower scores indicating less pain.

Secondary Outcome Measures

Name	Time	Method
Change in Interstitial Cystitis Problem Index	prior to initiating treatment and at the conclusion of 6 weeks of treatment	The changes in IC/PBS associated problems when treating interstitial cystitis/painful bladder syndrome with low-dose naltrexone as scored by the Interstitial Cystitis Problem Index, prior to initiating treatment and at the conclusion of 6 weeks of treatment. Scores are from 0-16, with lower scores indicating a better score, with fewer problems associated with IC/PBS. The change was calculated from two time points as the value prior to initiating treatment minus the value at the conclusion of 6 weeks of treatment.
Change in Urinary Frequency	prior to initiating treatment and at the conclusion of 6 weeks of treatment	The change in number of patient voids during the day when comparing LDN against placebo as determined from 24 hour bladder diary performed by patient prior to initiating treatment and at the conclusion of 6 weeks of treatment. The change was calculated from two time points as the value prior to initiating treatment minus the value at the conclusion of 6 weeks of treatment.
Change in Number of Nocturia	prior to initiating treatment and at the conclusion of 6 weeks of treatment	The change in number of patient voids during at night when comparing LDN against placebo as determined from 24 hour bladder diary performed by patient prior to initiating treatment and at the conclusion of 6 weeks of treatment. The change was calculated from two time points as the value prior to initiating treatment minus the value at the conclusion of 6 weeks of treatment.
Change in Pelvic Pain and Urgency/Frequency Symptoms	prior to initiating treatment and at the conclusion of 6 weeks of treatment	The change in pelvic pain and urgency/frequency symptoms as measured on the Pelvic Pain and Urgency/Frequency Patient Symptom Scale, prior to initiating treatment and at the conclusion of 6 weeks of treatment. Scores can range from 0-23, with higher scores indicating more severe symptoms associated with IC/PBS. The change was calculated from two time points as the value prior to initiating treatment minus the value at the conclusion of 6 weeks of treatment.
Change in Pelvic Pain and Urgency/Frequency Bother	prior to initiating treatment and at the conclusion of 6 weeks of treatment	The change in pelvic pain and urgency/frequency bother as measured on the Pelvic Pain and Urgency/Frequency Patient Symptom Scale, prior to initiating treatment and at the conclusion of 6 weeks of treatment. Scores can range from 0-12, with higher values corresponding to more bother from IC/PBS symptoms. The change was calculated from two time points as the value prior to initiating treatment minus the value at the conclusion of 6 weeks of treatment.
Patient Perceived Quality of Life: SF-36	six weeks	Patient perceived quality of life as measured by the medical outcomes study short form 36 (SF-36). Higher scores indicate a more favorable health status. There are 8 subscales, which when averaged, include a score from 0-100.
Adverse Effects	six weeks	The percentage of patients complaining of adverse effects from LDN including vivid dreams, nightmares, insomnia, GI disturbances such as stomach cramps or diarrhea, agitation, anxiety, flu-like symptoms and headaches.
Medication Tolerability	six weeks	The percentage of patients who discontinue the study medication measured by the tolerability survey.
Number of Days With Pain Medications	six weeks	The number of days with pain medication use while using LDN, as determined by a pain medication diary.