Low-dose Naltrexone for Bladder Pain Syndrome

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.

Study Overview

• Status: Suspended
• Conditions: Interstitial Cystitis; Bladder Pain Syndrome
• Intervention / Treatment: Drug: Naltrexone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gabrielle Hettie; Phone Number: 650-724-2091; Email: bhettie@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94304
      • Stanford Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low-dose naltrexone; 4.5mg of naltrexone to be taken one hour prior to bedtime nightly for 8 weeks.	Drug: Naltrexone; 4.5mg tab (low-dose) nightly
Placebo Comparator: Placebo; Placebo tablet (sugar-pill) to be taken one hour prior to bedtime nightly for 8 weeks.	Drug: Placebo; 1 tab nightly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of subjects in the LDN and placebo groups that are responders with greater than 20% reductions in 7-day average of worst daily Numeric Rating Scale of Pain scores after 8 weeks of treatment.	Will compare pre-intervention to week 8.

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Brief Pain Inventory Score	At pre-intervention to week 8.
Change in average frequency and nocturia during a 5-day voiding diary	At pre-intervention to week 8.
Change in Bladder Pain/Interstitial Cystitis Symptom Score	At pre-intervention to week 8
Change in O'Leary Sant symptom scores	At pre-intervention to week 8
Change in O'Leary Sant Problem Indices scores	At pre-intervention to week 8
Change in Global response assessment scale score	At pre-intervention to week 8
Change in PROMIS pain behavior score	At pre-intervention to week 8
Change in PROMIS physical function score	At pre-intervention to week 8
Change in PROMIS sleep dysfunction score	At pre-intervention to week 8
Change in PROMIS Sleep-Related Impairment	At pre-intervention to week 8
Change in PROMIS pain interference score	At pre-intervention to week 8
Change in PROMIS fatigue score	At pre-intervention to week 8
Change in PROMIS anxiety score	At pre-intervention to week 8
Change in PROMIS depression score	At pre-intervention to week 8

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Craig V Comiter, MD, Stanford University; Principal Investigator: Phil Hanno, MD, Stanford University; Principal Investigator: Jennifer M Hah, MD, MS, Stanford University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 29, 2020

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 16, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Cystitis; Somatoform Disorders; Cystitis, Interstitial; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: 57305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Should the study result be positive or promising, we would undertake a larger trial at which point we can reassess the sharing of IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No