To study the effect of TRH on opioid-induced respiratory depression in healthy volunteers.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
opiaat-geinduceerde ademdepressie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ventilation
Secondary outcome
-
Background summary
odern medicine relies heavily on opioids for suppression of moderate to severe
pain. Strong opioids are use observed during anesthesia to suppress autonomic
responses, during procedural sedation to reduce nociception, and given for
treatment of acute (postoperative) pain and chronic pain. However, the use of
opioids comes with serious side effects of which opioid-induced respiratory
depression (OIRD) is most dangerous. OIRD may be related to sedation, loss of
upper airway patency and central depression of rhythm generation. There are
various options to prevent or treat OIRD. We previously showed that the
K+-channel blocker GAL021 effectively reverses OIRD. GAL021 is still
experimental and will require many years of additional research before it may
be used in clinical practice. Alternatives to GAL021 that may be used
clinically are scarce. We recently tested the effect of the NMDA receptor
antagonist ketamine on OIRD (P16.117) and observed a partial relief of OIRD is
75% of volunteers (Fig. 1). Still, the use of ketamine is not without
consequences. First, it stimulates the sympathetic system and has psychomimetic
effects. Albeit mild, these effects preclude its general use. Second, ketamine
is a registered anesthetic and is given via the intravenous route. Hence, its
application in OIRD is limited to the perioperative setting.
One possible treatment of OIRD is with the hormone TRH (thyrotropin-releasing
hormone, tripeptide Glu-His-Pro-NH2). Few studies tested the effect of TRH on
breathing. In 1991, Nink et al. (Acta Physiol Scand 1991; 141: 309-318) studied
low-dose TRH (200 and 400 µg or 15 µg/min) on breathing in healthy volunteers
and observed brisk but short-lived respiratory effect. TRH is used in humans,
especially as diagnostic tool in endocrine disorders and for treatment of
spinal muscle atrophy (Tzeng et al. Am J Phys Med Rehab 2000; 79: 435-440).
In the current study, we will investigate the effect of intravenous TRH on
remifentanil-induced respiratory depression.
Study objective
To study the effect of TRH on opioid-induced respiratory depression in healthy
volunteers.
Study design
Double blind randomised
Intervention
Infusion of TRH and measurement of ventilation
Study burden and risks
Side effect are transitory and mild. The gain of this research is large with
possibly even the development of a complete new treatment strategy to overcome
OIRD. This is highly relevant taken the large opioid epidemic in the US.
Most common side effects of TRH reported in the literature are flushing,
nausea, vomiting, and small increases in blood pressure and heart rate. All
reported side effects were short-lived and mild.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
- Healthy male or female volunteers;
- Age: 18 - 40 years;
- Body mass index < 30 kg/m2;
- Able to give informed consent.
Exclusion criteria
- Known or suspected neuromuscular or a (family) history of any
neuromuscular disease;
- A history of allergic reaction to food or medication including study
medication;
- Any current or previous medical (including high blood pressure),
neurological or psychiatric illness (including a history of anxiety);
- Alcohol abuse (> 21 units/week);
- Illicit drug use in the past 30 days before inclusion;
- Pregnancy or lactation;
- Participation in any medical or drug trial in the month prior to the
current study.
Design
Recruitment
Medical products/devices used
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 | EUCTR2017-004973-15-NL |
| CCMO | NL64429.058.17 |