The objective of the study is to quantify the effect of pregabaline and lacosamide on oxycodone-induced respiratory depression.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Ademdepressie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Extrapolated ventilation at end-tidal PCO2 of 55 mmHg (VE55), 4-h following the
intake of oxycodone.
Secondary outcome
(1) Level of sedation; (2) Relief of nociception; (3) Occurrence of
nausea/vomiting;
(4) pupil diameter; (5) baseline ventilation.
Background 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.
Study objective
The objective of the study is to quantify the effect of pregabaline and
lacosamide on oxycodone-induced respiratory depression.
Study design
Double-blind, randomized cross-over design.
Intervention
Visit A: Oxycodone 10 mg tablet at t = 0 min + pregabaline 150 mg at t = 90 min;
Visit B: Oxycodone 10 mg tablet at t = 0 min + lacosamide 150 mg at t = 90 min.
Visit C (extra arm): Oxycodone 10 mg tablet at t = 0
Study burden and risks
Opioids produce several side effects, which are the topic of the current study.
Gaining information on these side effects, specifically respiratory depression,
especially in combination pain treatment, is of importance given the current
opioid epidemic and high number of opioid toxicities in the world. Since the
study is performed under highly controlled and monitored conditions, the
occurrence of temporary side effects will have limited impact on the subject.
During the study, we will closely monitor the subjects and treat side effects,
most importantly nausea by intravenous administration of an antiemetic.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
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 (incl.
paracetamol or other pain killers);
- 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.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-001603-40-NL |
| CCMO | NL81207.058.22 |