Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal

• Status: Not yet recruiting
• Trial end date: 2024-09-02
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Calgary
• Treatments: Benzoic Acid; Probenecid

Criteria

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.

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