NCT04939623

Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal

Recruiting now Phase 2 Last updated 30 March 2025

What this trial tests

Phase 2 trial testing Probenecid in Chronic Pain in 40 participants. Currently enrolling.

Timeline

31 October 2023

Primary endpoint
31 December 2025

31 December 2025

Quick facts

Lead sponsor	University of Calgary
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	40
Start date	31 October 2023
Primary completion	31 December 2025
Estimated completion	31 December 2025
Sites	1 location across Canada

Drugs / interventions tested

• Probenecid (probenecid) — full drug profile →

Conditions studied

• Chronic Pain — all drugs for Chronic Pain →
• Drug Dependence of Morphine Type — all drugs for Drug Dependence of Morphine Type →
• Symptom, Withdrawal — all drugs for Symptom, Withdrawal →

Sponsor

University of Calgary

Who can join

Adults 18 to 80, any sex, with Chronic Pain or Drug Dependence of Morphine Type. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Promising immunomodulators for management of substance and alcohol use disorders.
   Acuña AM, Park C, Leyrer-Jackson JM, Olive MF. · · 2024 · cited 5× · PMID 38803314 · DOI 10.1080/14656566.2024.2360653