Here we will perform a proof of concept study on the ability of the antidepressant tianeptine to prevent respiratory depression from the opioid alfentanil in humans.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Opioid geïnduceerde ademdepressie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the respiratory effects of an oral dose of tianeptine on alfentanil*
induced respiratory depression
Secondary outcome
To assess the antinociceptive effects of an oral dose of tianeptine during
alfentanil-infusion.
Background summary
Opioids induce potent analgesia but may simultaneously produce life threatening
respiratory depression. Currently a number of drugs are available that prevent
or reverse the respiratory effect of these potent analgesics with varying
success. There is evidence that the antidepressant agent tianeptine has
properties very similar to the ampakines and enhances respiratory output.
Tianeptine acts at AMPA (amino*3-hydroxy-5-methyl-D-aspartate) receptors in
neurons, similar to the ampakines. Glutaminergic transmission through AMPA
receptors within brainstem respiratory centers, for example the pre-Botzinger
complex, is essential for respiratory rhythmogenesis. Tianeptine enhances AMPA
receptor-mediated transmission by acting at allosteric sites; it increases AMPA
currents through kinase phosphorylation. At the same time glutamatergic
transmission at NMDA receptors is reduced by tianeptine, an action very similar
to that observed with the potent antidepressant ketamine, which has a tonic
effect on respiration.
Study objective
Here we will perform a proof of concept study on the ability of the
antidepressant tianeptine to prevent respiratory depression from the opioid
alfentanil in humans.
Study design
The study will have a double blind and randomized design.
Intervention
Intravenous administration of alfentanil by target controlled infusion (set to
achieve a concentration of 50 (first 8 subjects) and 100 (second group of 8
subjects) ng/ml).
Oral dose of Tianeptine (100 mg)
Study burden and risks
The study will be conducted in the anesthesiology department of a hospital,
where all necessary emergency procedures are in place. The study will be
conducted by researchers with experience in treating respiratory depression.
Naloxone injections will be available to treat urgent, severe respiratory
depression. Other support measures for breathing and hemodynamics will also be
available, such as maintenance of fluids, oxygen and vasopressors.
Cardiavascular emergency measures such as defibrillation, magnesium sulphate
(IV) and anti-arrhytmic drugs will also be available. The overall risk/benefit
assesment is considered acceptable under the conditions described above.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Age of 18 to 35 years (inclusive);;Body Mass Index (BMI) between 18 and 35 kg/m2 (inclusive) and body weight between 50 kg and 100 kg (inclusive);;Subject is able to read and understand the written consent form, complete study*related procedures, and communicate with the study staff;;Subject is willing to comply with study restrictions
Exclusion criteria
Clinically relevant abnormal history of physical and mental health, as determined by medical history taking and physical examinations obtained during the screening visit and/or prior to the administration of the initial dose of the study drug (as judged by the investigator); ;A semi recumbent systolic blood pressure of >160 mmHg and/or diastolic blood pressure of > 95 mmHg at screening; ;History of alcoholism or substance abuse within three years prior to screening; ;Positive pregnancy test; ;Subjects using more than 20 units of alcohol per week;
Use of medication during the study period;
If sexually active, the subject is not using oral contraceptives, or surgically sterilized; ;Subject has a history of severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-*prescription drugs or food; ;Participation in an investigational drug trial in the 2 months prior to administration of the initial dose of study drug or more than 5 times per year; ;Any other condition that in the opinion of the investigator would
complicate or compromise the study, or the wellbeing of the subject.
Design
Recruitment
Medical products/devices used
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-002974-33-NL |
| CCMO | NL45511.058.13 |
| OMON | NL-OMON21991 |