To demonstrate that combined phMRI/phMRS can characterize the dose-dependent neurometabolic response to S-ketamine.
ID
Source
Brief title
Condition
- Psychiatric and behavioural symptoms NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Change in levels of GABA, glutamate, and lactate in the mPFC;
* phMRI signal in the mPFC.
Secondary outcome
* Functional connectivity, with the prefrontal cortex as important region of
interest
* Score on a VAS, to quantify the subjective effect of S-ketamine
* CADSS to monitor changes in dissociative state due to placebo or ketamine
administration.
* Blood samples will be obtained at several time points to assess the plasma
concentration of S-ketamine and its active metabolite norketamine.
Background summary
Pharmacological magnetic resonance imaging (phMRI), which measures the blood
flow response to drug-induced neuronal activation, is a promising technique to
non-invasively assess the brain*s response to psychotropic medication. However,
phMRI measures are blood flow based and therefore often contaminated by
(systemic) cardiovascular effects frequently induced by psychotropic
medication. Magnetic resonance spectroscopy has been suggested as a technique
to more directly assess drug-induced neuronal activity and therefore allow a
more complete characterization of the brain response to psychotropic
medication. We hypothesise that concurrent measurements of the hemodynamic
response and glutamate/GABA levels (with MRS) during drug administration will
provide the much-needed information to interpret the underlying neuronal
contribution to the phMRI signal. The aim of the proposed study is to provide
evidence for this hypothesis.
Study objective
To demonstrate that combined phMRI/phMRS can characterize the dose-dependent
neurometabolic response to S-ketamine.
Study design
The study is a single-blind double-dose counterbalanced placebo-controlled
randomized crossover design.
Study burden and risks
After an initial intake session, participants will visit the laboratory site 3
times. Each visit they will receive a sub-anaesthetic dose of S-ketamine or
placebo intravenously, during a phMRS/phMRI scan.
On the day before each visit all participants will have to adhere to some
simple restrictions regarding medication, alcohol and drug intake, as this may
affect phMRI/phMRS scans. In the morning of each visit participants will have
to refrain from smoking and stimulant containing drinks. During each
experimental session, two IV lines will be placed to facilitate blood sampling
and S-ketamine administration. The most common side effects of sub-anaesthetic
doses of S-ketamine include nausea and psychotomimetic effects such as
dream-like states and vivid imagery. Importantly, the above-mentioned adverse
events rapidly decrease after discontinuation of administration of S-ketamine.
Considering the low dose (five to nine times lower than anaesthetic dose),
extensive exclusion criteria, screening procedure and constant monitoring of
the subjects, no serious side effects are expected. Additionally, a (resident)
anaesthesiologist will supervise S-ketamine administration. MRI is a safe
method with no long-term side effects.
Though the participants of this study will have no direct benefits from
participating, the results contribute to the exploration of the highly
promising imaging technique phMRS. The overall nature and extent of the added
risk associated with participation in the current study is to be classified as
negligible and the burden can be considered minimal.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
* Healthy volunteers between 18 and 55 years old;
* BMI between 18.5 and 25;
* Male or female;
* If female: using oral contraceptives and not in hormone-free week
during scanning.
Exclusion criteria
* (History of) psychiatric treatment, for which prescription medication is used;
* First-degree relative with (history of) schizophrenia or major depression;
* (History) of neurological disorders (including stroke, convulsion, epilepsy)
as well as concussion with loss of consciousness
* Contraindications for S-ketamine (e.g. allergy for S-ketamine, or one of the
inactive ingredients of this product, high BP (RRsystolic > 180 mmHg or
diastolic >100 mmHg), use of xantiderivatives or methylergometrine);
* Contraindications for 7T MRI (e.g. claustrophobia, osteosynthetic material,
pacemaker, artificial cardiac valves);
* (History of) drug (opiate, LSD, (meth)amphetamine, cocaine, solvents,
cannabis, or barbiturate) or alcohol dependence;
* Used psychotropic medication, or recreational drugs over a period of
1 week prior to each test session;
* Used alcohol within the last 24 hours prior to each test session;
Design
Recruitment
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 |
|---|---|
| CCMO | NL74447.018.20 |