Bladder Pain Syndrome, Interstitial Cystitis, Low-dose Naltrexone, Low Dose Naltrexone, Naltrexone, Painful Bladder Syndrome
Conditions
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.
Interventions
2mg of low-dose naltrexone nightly for 2 weeks, then 4mg of low-dose naltrexone nightly for 4 weeks
DRUGPlacebo oral tablet
1 capsule nighty for 2 weeks, then 2 capsules nightly for 4 weeks
Sponsors
Endeavor Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 110 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low-dose Naltrexone 2mg low-dose naltrexone capsules
low-dose naltrexone: 2mg of low-dose naltrexone nightly for 2 weeks, then 4mg of low-dose naltrexone nightly for 4 weeks | 1 |
| Placebo Placebo capsules
Placebo oral tablet: 1 capsule nighty for 2 weeks, then 2 capsules nightly for 4 weeks | 2 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Low-dose Naltrexone |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 8.5 | 52 years STANDARD_DEVIATION 6 | 52 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
Interstitial Cystitis Symptom Index
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.
Time frame: six weeks
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Interstitial Cystitis Symptom Index | 6 score on a scale |
| Placebo | Interstitial Cystitis Symptom Index | 5 score on a scale |
Primary
Visual Analog Scale
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.
Time frame: six weeks
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Visual Analog Scale | 0 score on a scale |
| Placebo | Visual Analog Scale | 0 score on a scale |
Secondary
Adverse Effects
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.
Time frame: six weeks
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low-dose Naltrexone | Adverse Effects | 0 Participants |
| Placebo | Adverse Effects | 0 Participants |
Secondary
Change in Interstitial Cystitis Problem Index
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.
Time frame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Change in Interstitial Cystitis Problem Index | 4 score on a scale |
| Placebo | Change in Interstitial Cystitis Problem Index | 11 score on a scale |
Secondary
Change in Number of Nocturia
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.
Time frame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Change in Number of Nocturia | 3 voids per night |
| Placebo | Change in Number of Nocturia | 2 voids per night |
Secondary
Change in Pelvic Pain and Urgency/Frequency Bother
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.
Time frame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Change in Pelvic Pain and Urgency/Frequency Bother | 1 score on a scale |
| Placebo | Change in Pelvic Pain and Urgency/Frequency Bother | 7 score on a scale |
Secondary
Change in Pelvic Pain and Urgency/Frequency Symptoms
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.
Time frame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Change in Pelvic Pain and Urgency/Frequency Symptoms | 3 score on a scale |
| Placebo | Change in Pelvic Pain and Urgency/Frequency Symptoms | 7 score on a scale |
Secondary
Change in Urinary Frequency
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.
Time frame: prior to initiating treatment and at the conclusion of 6 weeks of treatment
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Change in Urinary Frequency | 8 voids per day |
| Placebo | Change in Urinary Frequency | 11 voids per day |
Secondary
Medication Tolerability
The percentage of patients who discontinue the study medication measured by the tolerability survey.
Time frame: six weeks
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low-dose Naltrexone | Medication Tolerability | 0 Participants |
| Placebo | Medication Tolerability | 0 Participants |
Secondary
Number of Days With Pain Medications
The number of days with pain medication use while using LDN, as determined by a pain medication diary.
Time frame: six weeks
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Number of Days With Pain Medications | 13 days |
| Placebo | Number of Days With Pain Medications | 42 days |
Secondary
Patient Perceived Quality of Life: SF-36
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.
Time frame: six weeks
Population: Excluding one participant who withdrew from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Naltrexone | Patient Perceived Quality of Life: SF-36 | 86 score on a scale |
| Placebo | Patient Perceived Quality of Life: SF-36 | 84 score on a scale |