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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal

Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal in People With Chronic Pain Undergoing Voluntary Opioid Tapering: a Pilot Study

Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal (NCT04939623) is a Phase 2 interventional studying Chronic Pain and Drug Dependence of Morphine Type, sponsored by University of Calgary. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The proposed clinical trial will address the problem of opioid withdrawal. Opioids are essential for pain-relief in the short term, but their continued use is associated with a host of adverse effects. People living with chronic pain who were initiated on opioid therapy now find themselves with a major life-changing problem - dependence on opioid medications. Opioid withdrawal symptoms are a key barrier to decreasing or stopping their opioid medication. Currently, there are few medications that ameliorate the symptoms of opioid withdrawal. This problem is a major part of the opioid crisis in Canada, and impacts people across all demographics and socioeconomic status. A misconception is that only individuals with opioid use disorder are susceptible to opioid withdrawal; on the contrary, appropriate use of prescription opioids to manage pain can lead to significant symptoms of opioid withdrawal when it is reduced or stopped. Patients in Alberta who are at risk for opioid withdrawal, either from prescribed use or misuse will be primarily impacted by this trial. The investigators have recently explored the underlying causes of opioid withdrawal and identified an important target in the spinal cord that is responsible for producing withdrawal symptoms in rats and mice. The target, a protein called pannexin-1 (Panx1), is located throughout the body, specifically in the brain and spinal cord. Using sophisticated biochemical, genetic, and pharmacological techniques, the investigators demonstrated how Panx1 on immune cells is implicated in the production of opioid withdrawal symptoms after cessation of fentanyl and morphine in opioid dependent rodents. The investigators then attenuated these symptoms of withdrawal using probenecid, a drug which inherently blocks Panx1 activity. Because probenecid is a safe and clinically available drug, the findings could be immediately translated into clinical therapy to support people who are struggling with the symptoms of opioid withdrawal and provide clinicians with a safe and effective option for caring for this population.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Chronic Pain and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 40 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Adults with chronic pain. Age greater than or equal to 18 years on the day of enrolment. 2. Subjects are currently taking a daily opioid pain medication and planning to taper the dose. 3. Participants complete at least one voluntary opioid dose reduction in the twelve-week study period. 4. Glomerular filtration rate (GFR) \> 50 mL/min 5. Capable of providing willing to sign a consent form Who Should NOT Join This Trial: 1. Allergy to probenecid or related drugs 2. History of uric acid renal calculi, if known to be urate calculi. If unknown type, then any history of renal calculi. 3. Known G6PD deficiency 4. Active gout in any joint 5. Current use of drugs whose exposure may be prolonged, or risk of toxicity increased when used in combination with probenecid: 1. Penicillins, specifically ampicillin, penicillin G sodium, and piperacillin 2. Carbapenems, specifically doripenem and meropenem 3. Lorazepam, midazolam, nitrazepam 4. Ketorolac 5. Oseltamivir 6. Methotrexate 7. Mycophenolate 6. Current use of drugs which may mask symptoms of withdrawal: a. Clonidine, lofexidine, tizanidine 7. Current use of drugs which may diminish the effect of probenecid: a. High dose salicylates including greater than 325 mg PO daily of acetylsalicylic acid (ASA) 8. Pregnancy or breastfeeding 9. Any major comorbid medical condition which might impair follow-up or result in a safety risk to the participant 10. Participation in another clinical trial investigating a drug, medical device, or a medical procedure during the 30 days prior to enrolment. \- Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Adults with chronic pain. Age greater than or equal to 18 years on the day of enrolment. 2. Subjects are currently taking a daily opioid pain medication and planning to taper the dose. 3. Participants complete at least one voluntary opioid dose reduction in the twelve-week study period. 4. Glomerular filtration rate (GFR) \> 50 mL/min 5. Capable of providing informed consent Exclusion Criteria: 1. Allergy to probenecid or related drugs 2. History of uric acid renal calculi, if known to be urate calculi. If unknown type, then any history of renal calculi. 3. Known G6PD deficiency 4. Active gout in any joint 5. Current use of drugs whose exposure may be prolonged, or risk of toxicity increased when used in combination with probenecid: 1. Penicillins, specifically ampicillin, penicillin G sodium, and piperacillin 2. Carbapenems, specifically doripenem and meropenem 3. Lorazepam, midazolam, nitrazepam 4. Ketorolac 5. Oseltamivir 6. Methotrexate 7. Mycophenolate 6. Current use of drugs which may mask symptoms of withdrawal: a. Clonidine, lofexidine, tizanidine 7. Current use of drugs which may diminish the effect of probenecid: a. High dose salicylates including greater than 325 mg PO daily of acetylsalicylic acid (ASA) 8. Pregnancy or breastfeeding 9. Any major comorbid medical condition which might impair follow-up or result in a safety risk to the participant 10. Participation in another clinical trial investigating a drug, medical device, or a medical procedure during the 30 days prior to enrolment. \-

Treatments Being Tested

DRUG

Probenecid

The Investigators aim to recruit 40 participants who will be followed for 12 weeks in duration. Participants will be randomized in a 2:2:1 ratio to one of probenecid 500 mg, 1000 mg, or placebo PO BID for 12 weeks. Justification for use of a non-active placebo comparator includes the fact that this trial is meant to identify tolerability and safety of probenecid in a population of patients living with chronic pain, this will be best measured by comparing to a non-active placebo.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Richmond Road Diagnostic and Treatment Centre
Calgary, Alberta, Canada

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04939623), the sponsor (University of Calgary), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04939623 clinical trial studying?

The proposed clinical trial will address the problem of opioid withdrawal. Opioids are essential for pain-relief in the short term, but their continued use is associated with a host of adverse effects. People living with chronic pain who were initiated on opioid therapy now find themselves with a major life-changing problem - dependence on opioid medications. Opioid withdrawal symptoms are a key barrier to decreasing or stopping their opioid medication. Currently, there are few medications that ameliorate the symptoms of opioid withdrawal. This problem is a major part of the opioid crisis in C… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04939623?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04939623?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04939623. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04939623. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.