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

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. The hypothesis is 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.

Amendment:

In order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone was added as a visit 3. Since the procedures in this third arm will be identical to the two blinded arms, no changes will be made to any of the procedures apart from not administering any lacosamide or pregabalin.

Conditions

• Opioid-induced Respiratory Depression

Interventions

DRUG

Pregabalin 150mg

one capsule of 150mg 90 minutes after 10mg of oxycodone

DRUG

Oxycodone 10mg

one 10mg tablet

DRUG

Lacosamide 150 mg

one capsule of 150mg 90 minutes after 10mg of oxycodone

Sponsors & Collaborators

• Leiden University Medical Center

  lead OTHER

Principal Investigators

• Marieke Niesters, MD, PhD · Leiden University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-10-10

Primary Completion

2024-01-12

Completion

2024-01-12

Countries

• Netherlands

Study Locations