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TerminatedNCT04450316Updated Jul 10, 2026Results posted

Low-dose Naltrexone for Bladder Pain Syndrome

A Phase 2 interventional study of Naltrexone and Placebo in Bladder Pain Syndrome and Interstitial Cystitis, sponsored by Stanford University. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-10.

Sponsored by Stanford University · Phase 2, Interventional, and Treatment

Why this study was terminated
Study terminated due to early participant drop out
Phase
Phase 2
Study type
Interventional
Enrollment
29
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Bladder Pain Syndrome
  • Interstitial Cystitis
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
29 participants (actual)

Study arms

  • Active comparator
    Low-dose naltrexone

    4.5mg of naltrexone to be taken one hour prior to bedtime nightly for 8 weeks.

    Drug: Naltrexone

  • Placebo comparator
    Placebo

    Placebo tablet (sugar-pill) to be taken one hour prior to bedtime nightly for 8 weeks.

    Drug: Placebo

Interventions

  • DrugNaltrexone

    4.5mg tab (low-dose) nightly

  • DrugPlacebo

    1 tab nightly

05

What researchers measure

Primary outcomes

  1. The Numeric Rating Scale of Pain

    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.

    Time frame: 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.

Secondary outcomes

  1. Change in Brief Pain Inventory Score

    The Brief Pain Inventory score ranges from a minimum of 0 to a maximum of 10, with higher scores indicating worse pain intensity.

    Time frame: Comparing the average of 7 days of scores reported pre-intervention and the average of 7 days of score reported 8 weeks after intervention.

  2. Voiding Diary

    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.

    Time frame: Prior to treatment and after 8 weeks of treatment.

  3. Change in Bladder Pain/Interstitial Cystitis Symptom Score

    Total score ranges from 0 to 38. Higher values represent more symptoms of bladder pain associated with interstitial cystitis.

    Time frame: At pre-intervention to week 8

  4. Change in O'Leary Sant Symptom Scores

    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.

    Time frame: At pre-intervention to week 8

  5. Change in O'Leary Sant Problem Indices Scores

    Score ranges from 0 to 16 with higher scores representing that symptoms of interstitial cystitis are more problematic to the person with interstitial cystitis.

    Time frame: At pre-intervention to week 8

  6. Change in Global Response Assessment Scale Score

    Patient-reported outcome measure. 7-point scale (ranging from markedly worse -3 to markedly improved +3), used to evaluate overall symptom change after treatment.

    Time frame: At pre-intervention to week 8

  7. Change in PROMIS Pain Behavior Score

    Standardized metric (mean 50, standard deviation 10) assessing observable pain indicators, ranging from 20 to 80, with higher scores indicating more severe pain behavior.

    Time frame: At pre-intervention to week 8

  8. Change in PROMIS Physical Function Score

    Standardized metric (mean 50, standard deviation 10) assessing self-reported capability, ranging from 20 to 80, with higher scores indicating better physical function

    Time frame: At pre-intervention to week 8

  9. Change in PROMIS Sleep Dysfunction Score

    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.

    Time frame: At pre-intervention to week 8

  10. Change in PROMIS Sleep-Related Impairment

    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.

    Time frame: At pre-intervention to week 8

  11. Change in PROMIS Pain Interference Score

    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

    Time frame: At pre-intervention to week 8

  12. Change in PROMIS Fatigue Score

    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.

    Time frame: At pre-intervention to week 8

  13. Change in PROMIS Anxiety Score

    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.

    Time frame: At pre-intervention to week 8

  14. Change in PROMIS Depression Score

    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.

    Time frame: At pre-intervention to week 8

06

Results

Posted Jul 10, 2026
Limitations and caveats
Early termination leading to small number of subjects analyzed

Participant flow

Patients were screened for eligibility and consented if eligible. Individuals who are consented are considered enrolled under the protocol.

Participant flow — Overall Study
MilestoneLow-dose NaltrexonePlacebo
Started168
Completed22
Not completed146

Outcome measures

PrimaryThe Numeric Rating Scale of Pain

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.

Time frame:
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.
Reported as:
Count of participants · Participants
The Numeric Rating Scale of Pain
ParticipantsLow-dose NaltrexonePlacebo
The Numeric Rating Scale of Pain32
SecondaryChange in Brief Pain Inventory Score

The Brief Pain Inventory score ranges from a minimum of 0 to a maximum of 10, with higher scores indicating worse pain intensity.

Time frame:
Comparing the average of 7 days of scores reported pre-intervention and the average of 7 days of score reported 8 weeks after intervention.
Reported as:
Least squares mean · score on a scale
Change in Brief Pain Inventory Score
score on a scaleLow-dose NaltrexonePlacebo
Change in Brief Pain Inventory Score4.08 (2.83 to 5.33)5.69 (3.91 to 7.46)
SecondaryVoiding Diary

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.

Time frame:
Prior to treatment and after 8 weeks of treatment.
Reported as:
Least squares mean · voids per day
Voiding Diary
voids per dayLow-dose NaltrexonePlacebo
Voiding Diary9.55 (5.97 to 13.12)13.26 (8.13 to 18.38)
SecondaryChange in Bladder Pain/Interstitial Cystitis Symptom Score

Total score ranges from 0 to 38. Higher values represent more symptoms of bladder pain associated with interstitial cystitis.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in Bladder Pain/Interstitial Cystitis Symptom Score
score on a scaleLow-dose NaltrexonePlacebo
Change in Bladder Pain/Interstitial Cystitis Symptom Score25.21 (22.70 to 27.73)26.18 (22.62 to 29.73)
SecondaryChange in O'Leary Sant Symptom Scores

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.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in O'Leary Sant Symptom Scores
score on a scaleLow-dose NaltrexonePlacebo
Change in O'Leary Sant Symptom Scores11.69 (10.33 to 13.04)12.53 (10.37 to 14.70)
SecondaryChange in O'Leary Sant Problem Indices Scores

Score ranges from 0 to 16 with higher scores representing that symptoms of interstitial cystitis are more problematic to the person with interstitial cystitis.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in O'Leary Sant Problem Indices Scores
score on a scaleLow-dose NaltrexonePlacebo
Change in O'Leary Sant Problem Indices Scores11.64 (9.70 to 13.58)12.72 (9.97 to 15.47)
SecondaryChange in Global Response Assessment Scale Score

Patient-reported outcome measure. 7-point scale (ranging from markedly worse -3 to markedly improved +3), used to evaluate overall symptom change after treatment.

Time frame:
At pre-intervention to week 8
Reported as:
Mean · score on a scale
Change in Global Response Assessment Scale Score
score on a scaleLow-dose NaltrexonePlacebo
Change in Global Response Assessment Scale Score0.5 ± 1.180 ± 0.71
SecondaryChange in PROMIS Pain Behavior Score

Standardized metric (mean 50, standard deviation 10) assessing observable pain indicators, ranging from 20 to 80, with higher scores indicating more severe pain behavior.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Pain Behavior Score
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Pain Behavior Score56.89 (53.39 to 60.37)55.01 (50.08 to 59.95)
SecondaryChange in PROMIS Physical Function Score

Standardized metric (mean 50, standard deviation 10) assessing self-reported capability, ranging from 20 to 80, with higher scores indicating better physical function

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Physical Function Score
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Physical Function Score44.36 (39.19 to 49.53)41.86 (34.51 to 49.21)
SecondaryChange in PROMIS Sleep Dysfunction Score

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.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Sleep Dysfunction Score
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Sleep Dysfunction Score56.44 (51.22 to 61.66)60.01 (52.60 to 67.43)
SecondaryChange in PROMIS Sleep-Related Impairment

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.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Sleep-Related Impairment
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Sleep-Related Impairment59.16 (53.08 to 65.24)60.88 (52.25 to 69.51)
SecondaryChange in PROMIS Pain Interference Score

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

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Pain Interference Score
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Pain Interference Score62.57 (58.74 to 66.40)62.84 (57.42 to 68.26)
SecondaryChange in PROMIS Fatigue Score

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.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Fatigue Score
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Fatigue Score61.49 (57.40 to 65.58)63.86 (57.92 to 69.80)
SecondaryChange in PROMIS Anxiety Score

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.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Anxiety Score
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Anxiety Score60.53 (55.39 to 65.71)65.01 (57.65 to 72.38)
SecondaryChange in PROMIS Depression Score

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.

Time frame:
At pre-intervention to week 8
Reported as:
Least squares mean · score on a scale
Change in PROMIS Depression Score
score on a scaleLow-dose NaltrexonePlacebo
Change in PROMIS Depression Score59.10 (53.25 to 64.96)54.94 (46.53 to 63.35)

Adverse events

Collected over Adverse event data were collected for each patient over 8 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Low-dose Naltrexone0/16 (0%)0/16 (0%)3/16 (18.8%)
Placebo0/8 (0%)0/8 (0%)1/8 (12.5%)
Most frequent other events
Most frequent other events
EventLow-dose NaltrexonePlacebo
Medication Side EffectNervous system disorders3/160/8
Urinary Tract InfectionInfections and infestations1/161/8

Baseline characteristics

Age, Continuous
Age, Continuous(years)Low-dose NaltrexonePlaceboTotal
Mean37.9 ± 20.167.9 ± 13.343.2 ± 25.4
Sex: Female, Male
Sex: Female, Male(Participants)Low-dose NaltrexonePlaceboTotal
Female13518
Male336
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Low-dose NaltrexonePlaceboTotal
Hispanic or Latino213
Not Hispanic or Latino14721
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Low-dose NaltrexonePlaceboTotal
American Indian or Alaska Native000
Asian213
Native Hawaiian or Other Pacific Islander000
Black or African American000
White11516
More than one race011
Unknown or Not Reported314
Brief Pain Inventory Worst Pain
Brief Pain Inventory Worst Pain(units on a scale)Low-dose NaltrexonePlaceboTotal
Mean5.7 ± 2.66.7 ± 2.35.7 ± 2.5
07

Study locations

1 site
  • Stanford Health Care
    Stanford, California 94304, United States
08

References and documents

Publications

  • Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15. PubMed 24526250 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 23, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Should the study result be positive or promising, we would undertake a larger trial at which point we can reassess the sharing of IPD.

09

Registry details

Key details

Study ID
NCT04450316
Lead sponsor
Stanford University
Responsible party
Jennifer Hah (Assistant Professor, Stanford University) — Principal investigator
First posted
Jun 29, 2020
Start date
Oct 8, 2020
Primary completion
Jun 4, 2022
Completion
Jun 4, 2022
Results posted
Jul 10, 2026
Last update
Jul 10, 2026

Study contacts

Craig V Comiter, MD
principal investigator · Stanford University
Phil Hanno, MD
principal investigator · Stanford University
Jennifer M Hah, MD, MS
principal investigator · Stanford University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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