Combined Effect of Pregabalin and Oxycodone, and Lacosamide and Oxycodone, on Breathing

• Status: Not yet recruiting
• Trial end date: 2023-12-03
• Target enrollment: 0
• Participant gender: All

Summary

Opioids are commonly prescribed for moderate to severe pain. While initially intended for moderate to severe acute and cancer pain, opioids are currently frequently considered and prescribed in chronic noncancer pain. Due to the large increase in opioid prescription rate, the number of unintentional drug overdoses is rapidly increasing, not only in the Unites States but also in the Netherlands. A potential lethal consequence of an opioid overdose is opioid-induced respiratory depression. Additionally, it is well known that opioids are often used (and abused) in combination with other legal or illicit substances, for example alcohol, benzodiazepines, cannabis, neuropathic pain medication including the anticonvulsant pregabaline. There are no high-quality data on the interaction between oxycodone and (neuropathic pain) medication on the ventilatory control system. Case reports and randomized studies show that pregabalin induces respiratory depression when combined with opioids. Some alternatives to pregabalin may have a better safety profile. One such alternative is lacosamide, an antiepileptic with a different mode of action than pregabalin, and effective in the treatment of neuropathic pain. We hypothesize that in contrast to lacosamide, pregabalin will increase the respiratory depressant effect of low-dose oxycodone.

The objective of the study is to quantify the effect of pregabalin and lacosamide on oxycodone-induced respiratory depression.

24 participants will be screened beforehand if subjects meet the inclusion and exclusion criteria. If so, the subjects will visit the hospital twice. On both occasions, participants will take a 10 mg oxycodone tablet and 90 minutes after a capsule of pregabalin or lacosamide. The order of visits will be randomized. During the visits, at set time points the hypercapnic ventilatory response will be measured, relief of nociception, pupil diameter and several side effects other than respiratory depression. There will be a washout period of 7 days between study visits with the study ending after 2 visits.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Leiden University Medical Center
• Treatments: Lacosamide; Oxycodone; Pregabalin

Criteria

Inclusion Criteria:

• aged 18-45 years,

• body mass index < 30 kg.m-2,

• able to understand the written informed consent form,

• able to communicate with the staff,

• able and willing to complete the study procedures,

• signed the informed consent form.

Exclusion Criteria:

• Presence or history of any medical or psychiatric disease (incl. a history of substance abuse, anxiety, or the presence of a painful syndrome such as fibromyalgia);

• Use of any medication in the three months prior to the study which may influence the outcome of the study as judged by the investigator;

• Use of more than 21 alcohol units per week;

• A positive urinary drug test or a breath alcohol test at screening or on the morning of the experiment;

• Pregnancy, lactating or a positive pregnancy test on the morning of the experiment;

• Participation in another drug trial in the 60 days prior to dosing.