Clinical trial NCT02701933: Effects of Ketamine on Eye Movements, Perception and Brain Function
Official title: Effects of Ketamine on Eye Movements, Perception and Brain Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Functional Neuroimaging
Lead sponsor: University of Bonn
Sponsor class: OTHER
First posted: 2016-03-08
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: In this study, the investigators examine the effects of low-dose ketamine on different oculomotor, perceptual and cognitive functions. They also examine effects on concurrent brain activity using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). A sample of N=25 healthy, male participants is required to complete the study. The design is within-subjects, placebo-controlled, double-blind and cross-over. A targeted ketamine level in plasma of 100ng/ml is applied. It is hypothesised that ketamine, compared to placebo, will lead to changes in task performance and brain activity similar to those observed in patients with schizophrenia.

Detailed description: The uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been proposed as a model system of the symptoms of schizophrenia. To complement this model system and to allow neurobiological as well as translational studies, biomarkers are often applied to people under the influence of ketamine. Here, we apply oculomotor, perceptual and cognitive biomarkers to healthy human volunteers whilst they undergo BOLD fMRI at 3 Tesla field strength. We use a counter-balanced, placebo-controlled, double-blind, within-subjects design. A sample of 25 healthy participants is required. Participants will receive intravenous (IV) racemic ketamine (with a 100ng/ml target plasma concentration) on one of two assessment days and they will receive placebo (intravenous saline) on the other assessment day. BOLD fMRI will be carried out on a Siemens Trio scanner at the Life\&Brain Centre, Bonn. In addition to brain functional and cognitive, perceptual and oculomotor responses, we will also measure self-ratings of psychosis-like experiences. These will be obtained using the Psychotomimetic States Inventory (PSI; Mason et al 2008).

Eligibility criteria: Inclusion Criteria:

* MRI-suitability
* suitability for video-based combined pupil and corneal reflection (VCPCR) eye-tracking
* good command of German language
* willingness to take part

Exclusion Criteria:

* any current or history of axis I disorder diagnosis as assessed by the Mini-International Neuropsychiatric Interview (M.I.N.I.)
* any neurological conditions and heart conditions
* use of any prescription or non-prescription medication up to one week before participation
* personal history of head-injuries, loss of consciousness, eye surgery or impairment of vision (other than corrective lenses)
* any other relevant medical conditions such as high blood pressure
* positive urine drug test (Drug-Screen Multi "5T", nal von minden GmbH)
* history of drug use or current drug use
* under- or overweight (below 18.5 and above 24.9 body mass index (BMI) values)
* any diagnosis of psychotic disorders among first-degree relatives

Primary outcomes:
measure: Brain activity in cortical and subcortical areas as assessed using BOLD (blood oxygen level dependent) functional magnetic resonance imaging (fMRI) at 3 Tesla field strength
timeFrame: within 1 hour of start of IV infusion
Secondary outcomes:
measure: Psychotomimetic State Inventory (PSI)
timeFrame: within 1 hour of start of IV infusion
measure: Visual Analogue Rating Scales (VARS) from Norris 1971; self-rating scores of the subscales "mental sedation", "physical sedation", "tranquillisation" and "other feelings and attitudes"
timeFrame: within 1 hour of start of IV infusion
measure: d2 Attention Test, a measure of sustained attention
timeFrame: within 1 hour of start of IV infusion
measure: Recognition memory performance (latencies in ms)
timeFrame: after 5 days of washout period
measure: Recognition memory performance (percent correct responses)
timeFrame: after 5 days of washout period
measure: Smooth pursuit gain (%)
timeFrame: within 1 hour of start of IV infusion
measure: Smooth pursuit root mean square error (RMSE)
timeFrame: within 1 hour of start of IV infusion
measure: Smooth pursuit saccadic frequency (number per second)
timeFrame: within 1 hour of start of IV infusion
measure: Prosaccade latency (ms)
timeFrame: within 1 hour of start of IV infusion
measure: Prosaccade gain (%)
timeFrame: within 1 hour of start of IV infusion
measure: Prosaccade spatial error (%)
timeFrame: within 1 hour of start of IV infusion
measure: Prosaccade velocity (degrees per second)
timeFrame: within 1 hour of start of IV infusion
measure: Prosaccade error rate (%)
timeFrame: within 1 hour of start of IV infusion
measure: Antisaccade latency (ms)
timeFrame: within 1 hour of start of IV infusion
measure: Antisaccade gain (%)
timeFrame: within 1 hour of start of IV infusion
measure: Antisaccade spatial error (%)
timeFrame: within 1 hour of start of IV infusion
measure: Antisaccade velocity (degrees per second)
timeFrame: within 1 hour of start of IV infusion
measure: Antisaccade error rate (%)
timeFrame: within 1 hour of start of IV infusion
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University of Bonn
state: NRW
Study officials:
affiliation: Department of Psychology, University of Bonn
name: Ulrich Ettinger, PhD
role: PRINCIPAL_INVESTIGATOR
References: