Effects of Ketamine on Eye Movements, Perception and Brain Function

Not Applicable

Completed

• Conditions: Functional Neuroimaging
• Interventions: Drug: Ketamine; Drug: Saline

• Registration Number: NCT02701933
• Lead Sponsor: University of Bonn

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).

Study Timeline

• Study Start: 2014-04
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Study First Submitted: 2016-02-17
• Status Verified: 2016-03
• Study First Submitted QC: 2016-03-02
• Last Update Submitted: 2016-03-02
• Study First Posted: 2016-03-08
• Last Update Posted: 2016-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ketamine-Saline	Saline	Each participant receives both ketamine and placebo (saline) in randomised order in a repeated-measures design. In this arm, ketamine is administered on the first assessment and placebo (saline) is administered on the second assessment.
Saline-Ketamine	Saline	Each participant receives both ketamine and placebo (saline) in randomised order in a repeated-measures design. In this arm, placebo (saline) is administered on the first assessment and ketamine is administered on the second assessment.
Ketamine-Saline	Ketamine	Each participant receives both ketamine and placebo (saline) in randomised order in a repeated-measures design. In this arm, ketamine is administered on the first assessment and placebo (saline) is administered on the second assessment.
Saline-Ketamine	Ketamine	Each participant receives both ketamine and placebo (saline) in randomised order in a repeated-measures design. In this arm, placebo (saline) is administered on the first assessment and ketamine is administered on the second assessment.

Primary Outcome Measures

Name	Time	Method
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	within 1 hour of start of IV infusion

Secondary Outcome Measures

Name	Time	Method
Antisaccade spatial error (%)	within 1 hour of start of IV infusion
Prosaccade spatial error (%)	within 1 hour of start of IV infusion
Smooth pursuit root mean square error (RMSE)	within 1 hour of start of IV infusion
Smooth pursuit saccadic frequency (number per second)	within 1 hour of start of IV infusion
Psychotomimetic State Inventory (PSI)	within 1 hour of start of IV infusion
Visual Analogue Rating Scales (VARS) from Norris 1971; self-rating scores of the subscales "mental sedation", "physical sedation", "tranquillisation" and "other feelings and attitudes"	within 1 hour of start of IV infusion
d2 Attention Test, a measure of sustained attention	within 1 hour of start of IV infusion	The test requires the crossing out of the letter d combined with two dashes amidst letters d and p combined with one, two, three or four dashes and is a well-established measure of sustained attention
Recognition memory performance (latencies in ms)	after 5 days of washout period
Recognition memory performance (percent correct responses)	after 5 days of washout period
Smooth pursuit gain (%)	within 1 hour of start of IV infusion
Prosaccade latency (ms)	within 1 hour of start of IV infusion
Prosaccade velocity (degrees per second)	within 1 hour of start of IV infusion
Prosaccade gain (%)	within 1 hour of start of IV infusion
Prosaccade error rate (%)	within 1 hour of start of IV infusion
Antisaccade velocity (degrees per second)	within 1 hour of start of IV infusion
Antisaccade error rate (%)	within 1 hour of start of IV infusion
Antisaccade latency (ms)	within 1 hour of start of IV infusion
Antisaccade gain (%)	within 1 hour of start of IV infusion

Trial Locations

Locations (1)

University of Bonn; 🇩🇪 Bonn, NRW, Germany