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

• ClinicalTrials.gov Identifier: NCT05320991
• Recruitment Status: Completed
• First Posted: April 11, 2022
• Last Update Posted: April 18, 2022
• Sponsor: University Hospital, Bonn
• Information provided by (Responsible Party): Rene Hurlemann, University Hospital, Bonn

Tracking Information

• First Submitted Date: March 14, 2022
• First Posted Date: April 11, 2022
• Last Update Posted Date: April 18, 2022
• Actual Study Start Date: June 15, 2019
• Actual Primary Completion Date: September 27, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2022)

• Changes in Mentalizing/Theory of Mind [ Time Frame: During ketamine/placebo application in MRI ]
  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 [ Time Frame: During ketamine/placebo application in MRI ]
  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

Original Primary Outcome Measures (submitted: April 1, 2022)

• Changes in Mentalizing/Theory of Mind [ Time Frame: During ketamine/placebo application in MRI ]
  Over- and undermentalizing as characterized by the Movie for the assessment of social cognition (MASC). Higher scores on the "Mentalizing"-scale indicate better performance.
• Neural response to ketamine/placebo during social cognition [ Time Frame: During ketamine/placebo application in MRI ]
  fMRI imaging will be performed to measure blood oxygen level-dependent signal in response to mentalizing cues in the MASC-task.

Current Secondary Outcome Measures (submitted: April 11, 2022)

• Psychotic symptom load in PANSS-Questionnaire [ Time Frame: 10 minutes after cessation of MRI and ketamine/placebo application ]
  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) [ Time Frame: 20 minutes after cessation of MRI and ketamine/placebo application ]
  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

Original Secondary Outcome Measures (submitted: April 1, 2022)

• Psychotic symptom load in PANSS-Questionnaire [ Time Frame: 10 minutes after cessation of MRI and ketamine/placebo application ]
  Positive and negative symptoms measured with questionnaire used in schizophrenia-research (Positive and Negative Symptom Scale)
• Metacognitive-Questionnaire (MCQ) [ Time Frame: 20 minutes after cessation of MRI and ketamine/placebo application ]
  Metacognitive typology as assessed with the MCQ

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers
• Official Title: A Randomized Control Trial Employing fMRI to Investigate the Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

All investigators (except anesthesiologists) are blinded until fMRI data has been preprocessed

Primary Purpose: Basic Science

Condition

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

Intervention

• Drug: Ketamine
  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.
• Drug: Nacl 0.9%
  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).

Study Arms

• Placebo Comparator: Placebo
  Participants receive a saline-solution intravenously
  Intervention: Drug: Nacl 0.9%
• Experimental: Ketamine
  Participants receive ketamine (Plasma-level 100 ng/ml with an initial bolus administered as a 2 mg/ml solution)
  Intervention: Drug: Ketamine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 1, 2022): 70
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 27, 2020
• Actual Primary Completion Date: September 27, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 35 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: NCT05320991
• Other Study ID Numbers: #19-03-29 (METAKETA)
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rene Hurlemann, University Hospital, Bonn
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Bonn
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University Hospital, Bonn
• Verification Date: April 2022