Bladder Pain Syndrome, Interstitial Cystitis
Conditions
Brief summary
Interstitial cystitis/Bladder Pain Syndrome (IC/PBS) is a constellation of symptoms of pelvic discomfort that includes both bladder-related pain as well as urinary frequency, urgency, and nocturia in the absence of an identifiable etiology that affects likely more than 5.4 million patients in the United States. There is a significant overlap in patients with IC/PBS and those with fibromyalgia and chronic pelvic pain syndrome. Low-dose naltrexone (LDN) has been shown to be effective for the treatment of chronic pain conditions. The primary aim of this study is to evaluate if LDN improves pain scores and lower urinary tract symptoms in patients with IC/PBS. A secondary aim is to show that it has a low adverse event profile.
Interventions
DRUGNaltrexone
4.5mg tab (low-dose) nightly
DRUGPlacebo
1 tab nightly
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants will be randomized on a 1:1 ratio to either LDN or placebo. The randomization sequence will be logged by the study coordinator in a REDCap randomization log blinded to other research staff and clinical team and outcome assessors.
Intervention model description
Randomized placebo-controlled pilot study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women with non-Hunner and Hunner lesion disease * Meeting AUA definition of BPS: An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder associated with lower urinary tract symptoms of greater than 6 weeks duration in the absence of infection or other identifiable cause. * Stable treatment for 1 month * 7-day maximum of pain scores at least 4/10 on the numerical rating scale of pain in the bladder/pelvic area. Urinary frequency 8 or higher while awake. Nocturia 2 or higher. BPIC-SS 19. * Agreement to not take opioids through the duration of the trial
Exclusion criteria
* Substance Use Disorder Diagnosis including Opioid Use Disorder Diagnosis * Known allergy to naltrexone or naloxone * Participation in another clinical trial * Current or planned pregnancy, or breastfeeding * Chronic pain in another location of the body that is more severe than that related to BPS. * Any intravesical instillation in last 8 weeks * If on Elmiron, stable dose for last 3 months * If on amitriptyline, stable dose for last 3 months * Any botox within last 6 months * Treatment for Hunners in the last 6 months * Any new Interstim settings within last 3 months * Any new pelvic floor physical therapy in last 12 weeks * Any change in or new OTC meds over last 2 months. * Any pain interventions in the preceding 6 weeks (epidural steroid injection, sympathetic block, peripheral nerve block, lumbar medial branch blocks) * Opioids chronically for IC/BPS in the past unless have been off for 1 year * Recent short-term (within one week of enrollment) opioid use for flairs * No documented cystoscopy in the last 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Numeric Rating Scale of Pain | Will compare a 7-day average of pre-intervention Numeric Rating Scale of Pain scores to the 7-day average of post-intervention Numeric Rating Scale of Pain Scores after week 8 of treatment. | The Numeric Rating Scale (NRS) of Pain uses an 11-point likert scale. Scores ranges from a minimum of 0 (No pain) to a maximum of 10 (Worst Pain Imaginable). Higher scores indicate greater pain intensityThe proportion of subjects in the LDN and placebo groups that are responders with greater than 20% reductions in the worst daily Numeric Rating Scale of Pain scores after 8 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brief Pain Inventory Score | Comparing the average of 7 days of scores reported pre-intervention and the average of 7 days of score reported 8 weeks after intervention. | The Brief Pain Inventory score ranges from a minimum of 0 to a maximum of 10, with higher scores indicating worse pain intensity. |
| Voiding Diary | Prior to treatment and after 8 weeks of treatment. | The Voiding Diary assesses the frequency and amount an individual voids over the course of a 24 hour period. Study subjects indicate number of times they void in an hour and how much they urinate. Study subjects complete daily voiding diaries over the course of a 7 day period before and after the intervention period. Voiding frequency in a 24 hour period was assessed with possible range between 0 to 24 times per day. Participants were asked to complete a 7-day voiding diary at baseline and after 8 weeks of treatment. The average voiding frequency at baseline was compared to follow-up after 8 weeks of treatment. |
| Change in Bladder Pain/Interstitial Cystitis Symptom Score | At pre-intervention to week 8 | Total score ranges from 0 to 38. Higher values represent more symptoms of bladder pain associated with interstitial cystitis. |
| Change in O'Leary Sant Symptom Scores | At pre-intervention to week 8 | Scores range from 0-20 with higher scores representing more frequency of symptoms associated with interstitial cystitis such as urgency, frequency, nocturia (getting up at night to urinate), and pain or burning in the bladder. |
| Change in O'Leary Sant Problem Indices Scores | At pre-intervention to week 8 | Score ranges from 0 to 16 with higher scores representing that symptoms of interstitial cystitis are more problematic to the person with interstitial cystitis. |
| Change in Global Response Assessment Scale Score | At pre-intervention to week 8 | Patient-reported outcome measure. 7-point scale (ranging from markedly worse -3 to markedly improved +3), used to evaluate overall symptom change after treatment. |
| Change in PROMIS Pain Behavior Score | At pre-intervention to week 8 | Standardized metric (mean 50, standard deviation 10) assessing observable pain indicators, ranging from 20 to 80, with higher scores indicating more severe pain behavior. |
| Change in PROMIS Physical Function Score | At pre-intervention to week 8 | Standardized metric (mean 50, standard deviation 10) assessing self-reported capability, ranging from 20 to 80, with higher scores indicating better physical function |
| Change in PROMIS Sleep Dysfunction Score | At pre-intervention to week 8 | Standardized metric (mean 50, standard deviation 10) used to quantify self-reported sleep quality, depth, and restoration, ranging from 20 to 80, with a higher score indicating greater sleep disturbance. |
| Change in PROMIS Sleep-Related Impairment | At pre-intervention to week 8 | Sleep-related Impairment (SRI) score is a standardized, self-reported measure evaluating daytime alertness, sleepiness, and functional limitations over the past 7 days. It uses a T-score metric (mean of 50, standard deviation of 10), where higher scores indicate greater impairment. Scores range from 20-80. |
| Change in PROMIS Pain Interference Score | At pre-intervention to week 8 | The PROMIS Pain Interference (PI) score measures how much pain hinders a person's daily life-including physical, mental, emotional, and social activities-using a T-score metric where 50 is the average, and higher scores (e.g., 60+) indicate greater, more severe interference. Scores range from 20-80 |
| Change in PROMIS Fatigue Score | At pre-intervention to week 8 | The PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue score is a validated tool measuring the intensity, frequency, and impact of tiredness on daily life over the past seven days. It uses a T-score metric (mean=50, SD=10) where higher scores (e.g., 60+) indicate greater, more severe fatigue. Scores range from 20 to 80. |
| Change in PROMIS Anxiety Score | At pre-intervention to week 8 | Standardized metric (mean 50, standard deviation 10) assessing self-reported fear, anxious misery, and hyperarousal over the past 7 days, ranging from 20 to 80, with higher scores indicating more severe anxiety. |
| Change in PROMIS Depression Score | At pre-intervention to week 8 | Standardized metric (mean 50, standard deviation 10) assessing mood, self-view, and social cognition, ranging from 20 to 80, with higher scores indicating more severe depressive symptoms. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCraig V Comiter, MD
Stanford University
PRINCIPAL_INVESTIGATORPhil Hanno, MD
Stanford University
PRINCIPAL_INVESTIGATORJennifer M Hah, MD, MS
Stanford University
Participant flow
Recruitment details
Patients were screened for eligibility and consented if eligible. Individuals who are consented are considered enrolled under the protocol.
Pre-assignment details
5 participants did not complete the baseline assessments required before randomization and were excluded from the study before assignment to groups.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 43.2 years STANDARD_DEVIATION 25.4 |
| Brief Pain Inventory Worst Pain | 5.7 units on a scale STANDARD_DEVIATION 2.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 8 |
| other Total, other adverse events | 3 / 16 | 1 / 8 |
| serious Total, serious adverse events | 0 / 16 | 0 / 8 |
Outcome results
None listed