Clinical trial NCT04313972: IC PaIN Trial: Interstitial Cystitis Pain Improvement With Naltrexone
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Interstitial Cystitis
Painful Bladder Syndrome
Bladder Pain Syndrome
Low Dose Naltrexone
Low-dose Naltrexone
Naltrexone
Lead sponsor: Endeavor Health
Sponsor class: OTHER
First posted: 2020-03-18
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Patients aged eighteen and older
2. 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)
3. 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.
4. Have had a cystoscopy in the last 6 months prior to study entry to rule out confounding conditions
5. English speaking
6. Working telephone number
7. Able to provide a blood sample to evaluate liver enzymes
8. Able to attend research visits

Exclusion Criteria:

1. Patients under the age of 18
2. Patients with known liver disease, including total bilirubin \>1.2, AST (aspartate aminotransferase) \> 32, ALT (alanine transaminase) \> 54
3. Patients with known kidney disease
4. Patients who have thyroid disease and who are taking thyroid replacement medications
5. Patients with known neurologic disease affecting bladder function
6. Patients with known bladder or urethral cancer
7. Patients with bladder, urethral, or ureteral calculi
8. Patients who have had a positive urine culture or a clinical UTI (Urinary Tract Infection) in the past 6 weeks
9. Patients who are currently pregnant or breast feeding (15)
10. Patients who are actively using opioid analgesics
11. Patients with moderate-severe alcohol use disorder
12. Patients who are actively using sleep aids
13. 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.
14. Patients who have had a known adverse reaction to naltrexone
15. Patients who are acutely ill
16. Patients who are diagnosed with a significant psychological comorbidity that would interfere with study participation (32)
17. Patients who have had a bladder instillation or had oral medical treatment for IC/PBS in the past four weeks.
18. Patients diagnosed with other chronic pelvic pain syndromes, such as endometriosis
19. Patients who are unable to swallow pills/capsules
20. Patients who have had previous treatment with low-dose naltrexone
21. Patients who have previously scheduled surgeries or procedure during the study time period that would require analgesia.
22. 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.
23. Patients who are unwilling to have a serum blood test to assess serum transaminases and serum bilirubin.

Primary outcomes:
measure: Interstitial Cystitis Symptom Index
timeFrame: six weeks
measure: Visual Analog Scale
timeFrame: six weeks
Secondary outcomes:
measure: Change in Interstitial Cystitis Problem Index
timeFrame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
measure: Change in Urinary Frequency
timeFrame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
measure: Change in Number of Nocturia
timeFrame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
measure: Change in Pelvic Pain and Urgency/Frequency Symptoms
timeFrame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
measure: Change in Pelvic Pain and Urgency/Frequency Bother
timeFrame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
measure: Patient Perceived Quality of Life: SF-36
timeFrame: six weeks
measure: Adverse Effects
timeFrame: six weeks
measure: Medication Tolerability
timeFrame: six weeks
measure: Number of Days With Pain Medications
timeFrame: six weeks
Other outcomes:
Locations:
city: Skokie
country: United States
facility: Center for Pelvic Health at the NorthShore University HealthSystem
state: Illinois
Study officials:
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