Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal

Summary

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.

Conditions

• Chronic Pain
• Drug Dependence of Morphine Type
• Symptom, Withdrawal

Interventions

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.

Sponsors & Collaborators

• University of Calgary

  lead OTHER

Principal Investigators

• Lori Montgomery, MD · University of Calgary

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-10-31

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Drug

Yes

Countries

• Canada

Study Locations