Bladder Pain SyndromePhase 2NCT04450316
Low-dose Naltrexone for Bladder Pain Syndrome
A Phase 2 study testing Naltrexone in people with Bladder Pain Syndrome and Interstitial Cystitis, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Pain Syndrome, Interstitial Cystitis
- What is being tested?
- Naltrexone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2020to 4 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Low-dose Naltrexone for Bladder Pain Syndrome: A Randomized Placebo-controlled Prospective Pilot Trial
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.
- Conditions
- Bladder Pain Syndrome, Interstitial Cystitis
- Being tested
- Naltrexone, Placebo
- Medical subject headings
- Cystitis, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
4.5mg tab (low-dose) nightly
PlaceboDrug
1 tab nightly
| Study group | Role | What they receive |
|---|---|---|
| Low-dose naltrexone | Active comparator | 4.5mg of naltrexone to be taken one hour prior to bedtime nightly for 8 weeks. Receives: Drug: Naltrexone |
| Placebo | Placebo comparator | Placebo tablet (sugar-pill) to be taken one hour prior to bedtime nightly for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (14)
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.
Measured: Comparing the average of 7 days of scores reported pre-intervention and the average of 7 days of score reported 8 weeks after intervention.
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.
Measured: Prior to treatment and after 8 weeks of treatment.
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.
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 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
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
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
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
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.
Measured: At pre-intervention to week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2020
- Study start8 Oct 2020
- Primary completion4 Jun 2022
- Study completion4 Jun 2022
Why it stopped: Study terminated due to early participant drop out
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bladder Pain SyndromeStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized placebo-controlled pilot study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Hah, Stanford University
- Investigators
- Craig V Comiter, MD, Principal investigator, Stanford UniversityPhil Hanno, MD, Principal investigator, Stanford UniversityJennifer M Hah, MD, MS, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04450316
- Sponsor's protocol ID
- 57305
- Status last verified
- Jun 2026
- First submitted
- 24 Jun 2020
- Last updated
- 10 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
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 at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-dose Naltrexone for Bladder Pain Syndrome: A Randomized Placebo-controlled Prospective Pilot Trial
- ClinicalTrials.gov ID
- NCT04450316
- Acronym / sponsor ID
- 57305
- Conditions
- Bladder Pain Syndrome, Interstitial Cystitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to early participant drop out
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 8 Oct 2020 (actual)
- Primary completion
- 4 Jun 2022 (actual)
- Study completion
- 4 Jun 2022 (actual)
- First posted
- 29 Jun 2020 (actual)
- Results
- Posted 10 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized placebo-controlled pilot study
| Arm | Type | Receives |
|---|---|---|
| Low-dose naltrexone | Active comparator | Drug: Naltrexone4.5mg of naltrexone to be taken one hour prior to bedtime nightly for 8 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablet (sugar-pill) to be taken one hour prior to bedtime nightly for 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naltrexone4.5mg tab (low-dose) nightly | Drug | Low-dose naltrexone |
| Placebo1 tab nightly | Drug | Placebo |
Primary outcome
The Numeric Rating Scale of Pain
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.
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.
14 secondary outcomes
Change in Brief Pain Inventory Score
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.
Voiding Diary
Time frame: Prior to treatment and after 8 weeks of treatment.
Change in Bladder Pain/Interstitial Cystitis Symptom Score
Time frame: At pre-intervention to week 8
Change in O'Leary Sant Symptom Scores
Time frame: At pre-intervention to week 8
Change in O'Leary Sant Problem Indices Scores
Time frame: At pre-intervention to week 8
Change in Global Response Assessment Scale Score
Time frame: At pre-intervention to week 8
Change in PROMIS Pain Behavior Score
Time frame: At pre-intervention to week 8
Change in PROMIS Physical Function Score
Time frame: At pre-intervention to week 8
Change in PROMIS Sleep Dysfunction Score
Time frame: At pre-intervention to week 8
Change in PROMIS Sleep-Related Impairment
Time frame: At pre-intervention to week 8
Change in PROMIS Pain Interference Score
Time frame: At pre-intervention to week 8
Change in PROMIS Fatigue Score
Time frame: At pre-intervention to week 8
Change in PROMIS Anxiety Score
Time frame: At pre-intervention to week 8
Change in PROMIS Depression Score
Time frame: At pre-intervention to week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24526250Younger 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.
- Individual participant dataSharing planned: 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.
Related trials for Bladder Pain Syndrome
Enrolling by invitationObservational study
Migraine Medication Effects on Urinary Symptoms
Overactive Bladder, Bladder Pain Syndrome
Recruiting
EPPIC: Easing Pelvic Pain Interventions Clinical Research Program
Urologic Chronic Pelvic Pain Syndrome (UCPPS), Interstitial Cystitis
Recruiting
Investigation of PEMF Therapy for Female Patients With IC/BPS
Interstitial Cystitis, Chronic Interstitial Cystitis
Recruiting
Aerobic Exercise and Connective Tissue Massage in Painful Bladder Syndrome
Bladder Pain Syndrome, Painful Bladder Syndrome
RecruitingPhase 2/3
Amniotic Membrane Therapy for Interstitial Cystitis/Painful Bladder Syndrome
Interstitial Cystitis, Painful Bladder Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig V Comiter, MD principal investigator
Stanford University
Phil Hanno, MD principal investigator
Stanford University
Jennifer M Hah, MD, MS principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naltrexone in people with Bladder Pain Syndrome and Interstitial Cystitis, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Numeric Rating Scale of Pain (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04450316, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.