Effects of Ketamine on Eye Movements, Perception and Brain Function

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.

Study Overview

• Status: Completed
• Conditions: Functional Neuroimaging
• Intervention / Treatment: Drug: Ketamine; Drug: Saline

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Bonn, NRW, Germany, 53111
      • University of Bonn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Ketamine-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.	Drug: Ketamine; Racemic ketamine, intravenous, at a concentration of 10mg ketamine per 50ml infusion; Other Names: Ketamin Ratiopharm; Drug: Saline; Saline, intravenous infusion; Other Names: Kochsalzloesung
Other: Saline-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.	Drug: Ketamine; Racemic ketamine, intravenous, at a concentration of 10mg ketamine per 50ml infusion; Other Names: Ketamin Ratiopharm; Drug: Saline; Saline, intravenous infusion; Other Names: Kochsalzloesung

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	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	within 1 hour of start of IV infusion
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
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
Prosaccade latency (ms)		within 1 hour of start of IV infusion
Prosaccade gain (%)		within 1 hour of start of IV infusion
Prosaccade spatial error (%)		within 1 hour of start of IV infusion
Prosaccade velocity (degrees per second)		within 1 hour of start of IV infusion
Prosaccade 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
Antisaccade spatial error (%)		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

Collaborators and Investigators

• Sponsor: University of Bonn
• Investigators: Principal Investigator: Ulrich Ettinger, PhD, Department of Psychology, University of Bonn

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: March 2, 2016
• First Posted (Estimate): March 8, 2016

Study Record Updates

• Last Update Posted (Estimate): March 8, 2016
• Last Update Submitted That Met QC Criteria: March 2, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: #14-03-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No