Effects of Ketamine on Eye Movements, Perception and Brain Function

• ClinicalTrials.gov Identifier: NCT02701933
• Recruitment Status: Completed
• First Posted: March 8, 2016
• Last Update Posted: March 8, 2016
• Sponsor: University of Bonn
• Information provided by (Responsible Party): Ulrich Ettinger, University of Bonn

Tracking Information

• First Submitted Date: February 17, 2016
• First Posted Date: March 8, 2016
• Last Update Posted Date: March 8, 2016
• Study Start Date: April 2014
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 2, 2016): 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 [ Time Frame: within 1 hour of start of IV infusion ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: March 2, 2016)

• Psychotomimetic State Inventory (PSI) [ Time Frame: 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" [ Time Frame: within 1 hour of start of IV infusion ]
• d2 Attention Test, a measure of sustained attention [ Time Frame: 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) [ Time Frame: after 5 days of washout period ]
• Recognition memory performance (percent correct responses) [ Time Frame: after 5 days of washout period ]
• Smooth pursuit gain (%) [ Time Frame: within 1 hour of start of IV infusion ]
• Smooth pursuit root mean square error (RMSE) [ Time Frame: within 1 hour of start of IV infusion ]
• Smooth pursuit saccadic frequency (number per second) [ Time Frame: within 1 hour of start of IV infusion ]
• Prosaccade latency (ms) [ Time Frame: within 1 hour of start of IV infusion ]
• Prosaccade gain (%) [ Time Frame: within 1 hour of start of IV infusion ]
• Prosaccade spatial error (%) [ Time Frame: within 1 hour of start of IV infusion ]
• Prosaccade velocity (degrees per second) [ Time Frame: within 1 hour of start of IV infusion ]
• Prosaccade error rate (%) [ Time Frame: within 1 hour of start of IV infusion ]
• Antisaccade latency (ms) [ Time Frame: within 1 hour of start of IV infusion ]
• Antisaccade gain (%) [ Time Frame: within 1 hour of start of IV infusion ]
• Antisaccade spatial error (%) [ Time Frame: within 1 hour of start of IV infusion ]
• Antisaccade velocity (degrees per second) [ Time Frame: within 1 hour of start of IV infusion ]
• Antisaccade error rate (%) [ Time Frame: within 1 hour of start of IV infusion ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of Ketamine on Eye Movements, Perception and Brain Function
• Official Title: Effects of Ketamine on Eye Movements, Perception and Brain Function
• 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Functional Neuroimaging

Intervention

• Drug: Ketamine
  Racemic ketamine, intravenous, at a concentration of 10mg ketamine per 50ml infusion
  Other Name: Ketamin Ratiopharm
• Drug: Saline
  Saline, intravenous infusion
  Other Name: Kochsalzloesung

Study Arms

• 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.
  Interventions:

  • Drug: Ketamine
  • Drug: Saline
• 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.
  Interventions:

  • Drug: Ketamine
  • Drug: Saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 2, 2016): 24
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02701933
• Other Study ID Numbers: #14-03-20
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Ulrich Ettinger, University of Bonn
• Study Sponsor: University of Bonn
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Bonn
• Verification Date: March 2016