IC PaIN Trial: Interstitial Cystitis Pain Improvement With Naltrexone

April 26, 2023 updated by: Ghazaleh Rostami Nia, NorthShore University HealthSystem

IC PaIN Trial: Interstitial Cystitis Pain Improvement With Naltrexone, the Effect of Low Dose Naltrexone on Symptoms and Pain of Patients With Interstitial Cystitis/Painful Bladder Syndrome a Randomized Placebo-controlled Prospective Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Nani P Moss, MD, MPH
Phone Number: 224-251-2374
Email: nmoss2@northshore.org

Study Contact Backup

Name: Roger P Goldberg, MD, MPH
Phone Number: 224-251-2374
Email: rgoldberg@northshore.org

Study Locations

United States
- Illinois
  - Skokie, Illinois, United States, 60076
    - Center for Pelvic Health at the NorthShore University HealthSystem

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 108 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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> 32, ALT> 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 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Quadruple

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Placebo capsules	Drug: Placebo oral tablet 1 capsule nighty for 2 weeks, then 2 capsules nightly for 4 weeks
Experimental: Low-dose naltrexone 2mg low-dose naltrexone capsules	Drug: low-dose naltrexone 2mg of low-dose naltrexone nightly for 2 weeks, then 4mg of low-dose naltrexone nightly for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interstitial Cystitis Symptom Index Time Frame: six weeks	The effect of LDN in decreasing symptoms associated with IC/PBS 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.	six weeks
Visual analog scale Time Frame: 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 100, with lower scores indicating less pain.	six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interstitial Cystitis Problem Index Time Frame: six weeks	The decrease in IC/PBS associated problems when treating interstitial cystitis/painful bladder syndrome with low-dose naltrexone as scored by the Interstitial Cystitis Problem Index. Scores are from 0-16, with lower scores indicating a better score, with fewer problems associated with IC/PBS.	six weeks
Urinary frequency Time Frame: six weeks	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.	six weeks
Nocturia Time Frame: six weeks	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.	six weeks
pelvic pain and urgency/frequency symptoms Time Frame: six weeks	The change in pelvic pain and urgency/frequency symptoms as measured on the Pelvic Pain and Urgency/Frequency Patient Symptom Scale. Scores can range from 0-23, with higher scores indicating more severe symptoms associated with IC/PBS.	six weeks
pelvic pain and urgency/frequency bother Time Frame: six weeks	The change in pelvic pain and urgency/frequency bother as measured on the Pelvic Pain and Urgency/Frequency Patient Symptom Scale. Scores can range from 0-12, with higher values corresponding to more bother from IC/PBS symptoms.	six weeks
Patient perceived changes in quality of life: SF-36 Time Frame: six weeks	Patient perceived changes in 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.	six weeks
Adverse effects Time Frame: 6 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.	6 weeks
Medication tolerability Time Frame: 6 weeks	Patient tolerability of low-dose naltrexone using a tolerability survey, as well as instructing the patient to return any remaining medication at the end of the 6 week study period	6 weeks
Change in pain medications Time Frame: 6 weeks	The decrease in use of pain medications while using LDN as determined by a pain medication diary	6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NorthShore University HealthSystem

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 7, 2021

Primary Completion (Actual)

January 23, 2023

Study Completion (Actual)

February 23, 2023

Study Registration Dates

First Submitted

March 16, 2020

First Submitted That Met QC Criteria

March 16, 2020

First Posted (Actual)

March 18, 2020

Study Record Updates

Last Update Posted (Actual)

April 28, 2023

Last Update Submitted That Met QC Criteria

April 26, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

EH20-127

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

IC PaIN Trial: Interstitial Cystitis Pain Improvement With Naltrexone