Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

Social Cognition Clinical Trial

— METAKETAII  

Official title:

A Randomized Control Trial Employing fMRI to Investigate the Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05320991
• Other study ID #: #19-03-29 (METAKETA)
• Status: Completed
• Phase: Phase 4
• Start date: June 15, 2019
• Est. completion date: September 27, 2020

Study information

• Verified date: April 2022
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: September 27, 2020
• Est. primary completion date: September 27, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Mental Disorders
• Psychotic Disorders
• 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.
• 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).

Locations

Country	Name	City	State
Germany	Department of Psychiatry and Psychotherapy, University Hospital Bonn	Bonn

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	During ketamine/placebo application in MRI
Primary	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	During ketamine/placebo application in MRI
Secondary	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.	10 minutes after cessation of MRI and ketamine/placebo application
Secondary	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	20 minutes after cessation of MRI and ketamine/placebo application

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