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Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers (METAKETAII)

Primary Purpose

Ketamine-Induced Psychotic Disorder, Social Cognition, Theory of Mind

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Ketamine
Nacl 0.9%
Sponsored by
University Hospital, Bonn
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Ketamine-Induced Psychotic Disorder focused on measuring ketamine, fMRI, psychosis, mentalizing, social cognition, metacognition

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Potential participants are excluded based on the following criteria:

  • history of psychiatric/neurological disorder (self and first-degree relatives)
  • learning disabilities, or loss of consciousness for more than 5 minutes
  • history of alcohol or drug abuse within the last 12 months
  • history of ketamine abuse
  • history of complications during anesthesia (self and first-degree relatives)
  • serious physical illness
  • claustrophobia
  • color-blindness
  • metalliferous implant
  • visual impairments other than corrective lenses
  • injury or disease of the inner ear with loss of hearing
  • consumption of any prescription or over-the-counter medication 3 days previous to the examination
  • pregnancy
  • currently breastfeeding a baby
  • hypotension (blood pressure < 100/60)
  • hypertension (blood pressure > 140/90)
  • underweight (BMI <17)
  • overweight (BMI ≥30)

Recruited participants are required to meet the following criteria:

  • height between 150 and 195 cm
  • bodyweight between 50 and 99kg
  • male or female
  • right-handed
  • physically, neurologically and psychiatrically healthy
  • non-smoker
  • normal or corrected-to-normal eye-sight
  • good command of German language

Sites / Locations

  • Department of Psychiatry and Psychotherapy, University Hospital Bonn

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Ketamine

Arm Description

Participants receive a saline-solution intravenously

Participants receive ketamine (Plasma-level 100 ng/ml with an initial bolus administered as a 2 mg/ml solution)

Outcomes

Primary Outcome Measures

Changes in Mentalizing/Theory of Mind
Over- and undermentalizing as characterized by the Movie for the assessment of social cognition (MASC). Higher scores on the "Mentalizing"-scale indicate better performance. Scores are divded between 4 scales (Mentalizing, No Mentalizing, Overmentalizing, Undermentalizing), each ranging from 0 to 27. Higher scores in one of the scales pertaining to "no Mentalizing, Overmentalizing or Undermentalizing mean a deficiency in mentalizing skills.
Neural response to ketamine/placebo during social cognition
fMRI imaging will be performed to measure blood oxygen level-dependent (BOLD) signal in response to mentalizing cues in the MASC-task under ketamine/placebo. BOLD-signal will be measured with T2-weighted images in a 3T MRI. Data will be analyzed using SPM 12 in MATLAB. Deviations in BOLD-activity under ketamine compared to placebo (higher or lower activity of certain voxels/clusters compared all other voxels in the brain) will mean a change in neural response due to the effect of the substance

Secondary Outcome Measures

Psychotic symptom load in PANSS-Questionnaire
Positive and negative symptoms measured with questionnaire used in schizophrenia-research (Positive and Negative Symptom Scale). The PANSS uses a scale ranging from 1 to 7 in three different subscales (positive, 7 items; negative, 7 items; disorganized, 16 items). Higher numbers mean more psychotic symptoms.
Metacognitive-Questionnaire (MCQ)
Metacognitive typology as assessed with the MCQ. The MCQ is a questionnaire containing 30 items, based on a 4-point Likert scale (dont agree - strongly agree) from 1 to 4. It measures metacognitive ability in 5 subscales, each containing 6 items (Uncontrollability and Danger, Cognitive Self-Consciousness, Need to control thoughts, Positive Beliefs, Cognitive Confidence). This is a short form of the widely used Metacognitions Questionnaire that measures individual differences in a selection of metacognitive judgments and monitoring tendencies considered important in the metacognitive model of psychological disorders

Full Information

First Posted
March 14, 2022
Last Updated
April 11, 2022
Sponsor
University Hospital, Bonn
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1. Study Identification

Unique Protocol Identification Number
NCT05320991
Brief Title
Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers
Acronym
METAKETAII
Official Title
A Randomized Control Trial Employing fMRI to Investigate the Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 15, 2019 (Actual)
Primary Completion Date
September 27, 2020 (Actual)
Study Completion Date
September 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Bonn

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Antipsychotic medication shows generally good effect sizes when looking at reduction of positive psychotic symptoms of schizophrenia, such as paranoia or delusion. However, social functioning often remains deficient in patients, meaning dopamine-receptor antagonists are not sufficient in treatment of people with schizophrenia. A naturalistic video-based paradigm, named MASC has been used in the past to model over- and undermentalizing in patients with autism spectrum disorder and schizophrenia, since deficits in mentalizing can be explained by either overinterpreting a social situation (e.g. paranoid thoughts about intentions of others towards self) or by lacking the skill to read intentions of others. To find out whether experimental manipulation via a non-competetive N-methyl-D-aspartate antagonist can induce difficulties with social cognition similar to those observed in people with schizophrenia, the investigators will conduct a RCT applying either ketamine or a placebo intravenously while participants are completing the above mentioned mentalizing task in the fMRI-scanner.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketamine-Induced Psychotic Disorder, Social Cognition, Theory of Mind
Keywords
ketamine, fMRI, psychosis, mentalizing, social cognition, metacognition

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
All investigators (except anesthesiologists) are blinded until fMRI data has been preprocessed
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants receive a saline-solution intravenously
Arm Title
Ketamine
Arm Type
Experimental
Arm Description
Participants receive ketamine (Plasma-level 100 ng/ml with an initial bolus administered as a 2 mg/ml solution)
Intervention Type
Drug
Intervention Name(s)
Ketamine
Intervention Description
Ketamine is applied with a Graseby 3500 intravenous infusion pump controlled by the STANPUMP software (Steven Shafer, M.D., Anesthesiology Service, PAVAMC 3801 Miranda Ave., Palo Alto, USA). Target plasma levels are 100 ng/ml with an initial bolus administered as a 2 mg/ml solution.
Intervention Type
Drug
Intervention Name(s)
Nacl 0.9%
Intervention Description
Saline solution will also be applied with the Graseby 3500 intravenous infusion pump controlled by the STANPUMP software (Steven Shafer, M.D., Anesthesiology Service, PAVAMC 3801 Miranda Ave., Palo Alto, USA).
Primary Outcome Measure Information:
Title
Changes in Mentalizing/Theory of Mind
Description
Over- and undermentalizing as characterized by the Movie for the assessment of social cognition (MASC). Higher scores on the "Mentalizing"-scale indicate better performance. Scores are divded between 4 scales (Mentalizing, No Mentalizing, Overmentalizing, Undermentalizing), each ranging from 0 to 27. Higher scores in one of the scales pertaining to "no Mentalizing, Overmentalizing or Undermentalizing mean a deficiency in mentalizing skills.
Time Frame
During ketamine/placebo application in MRI
Title
Neural response to ketamine/placebo during social cognition
Description
fMRI imaging will be performed to measure blood oxygen level-dependent (BOLD) signal in response to mentalizing cues in the MASC-task under ketamine/placebo. BOLD-signal will be measured with T2-weighted images in a 3T MRI. Data will be analyzed using SPM 12 in MATLAB. Deviations in BOLD-activity under ketamine compared to placebo (higher or lower activity of certain voxels/clusters compared all other voxels in the brain) will mean a change in neural response due to the effect of the substance
Time Frame
During ketamine/placebo application in MRI
Secondary Outcome Measure Information:
Title
Psychotic symptom load in PANSS-Questionnaire
Description
Positive and negative symptoms measured with questionnaire used in schizophrenia-research (Positive and Negative Symptom Scale). The PANSS uses a scale ranging from 1 to 7 in three different subscales (positive, 7 items; negative, 7 items; disorganized, 16 items). Higher numbers mean more psychotic symptoms.
Time Frame
10 minutes after cessation of MRI and ketamine/placebo application
Title
Metacognitive-Questionnaire (MCQ)
Description
Metacognitive typology as assessed with the MCQ. The MCQ is a questionnaire containing 30 items, based on a 4-point Likert scale (dont agree - strongly agree) from 1 to 4. It measures metacognitive ability in 5 subscales, each containing 6 items (Uncontrollability and Danger, Cognitive Self-Consciousness, Need to control thoughts, Positive Beliefs, Cognitive Confidence). This is a short form of the widely used Metacognitions Questionnaire that measures individual differences in a selection of metacognitive judgments and monitoring tendencies considered important in the metacognitive model of psychological disorders
Time Frame
20 minutes after cessation of MRI and ketamine/placebo application

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Potential participants are excluded based on the following criteria: history of psychiatric/neurological disorder (self and first-degree relatives) learning disabilities, or loss of consciousness for more than 5 minutes history of alcohol or drug abuse within the last 12 months history of ketamine abuse history of complications during anesthesia (self and first-degree relatives) serious physical illness claustrophobia color-blindness metalliferous implant visual impairments other than corrective lenses injury or disease of the inner ear with loss of hearing consumption of any prescription or over-the-counter medication 3 days previous to the examination pregnancy currently breastfeeding a baby hypotension (blood pressure < 100/60) hypertension (blood pressure > 140/90) underweight (BMI <17) overweight (BMI ≥30) Recruited participants are required to meet the following criteria: height between 150 and 195 cm bodyweight between 50 and 99kg male or female right-handed physically, neurologically and psychiatrically healthy non-smoker normal or corrected-to-normal eye-sight good command of German language
Facility Information:
Facility Name
Department of Psychiatry and Psychotherapy, University Hospital Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://sites.google.com/view/bonnsocialneuroscienceunit
Description
Related Info

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Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

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