Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

NCT05320991 | Completed Phase 4

• 1 other identifier: #19-03-29 (METAKETA)
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

ketamine; fMRI; psychosis; mentalizing; social cognition; metacognition

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• Psychotic symptom load in PANSS-Questionnaire

  10 minutes after cessation of MRI and ketamine/placebo application

• Metacognitive-Questionnaire (MCQ)

  20 minutes after cessation of MRI and ketamine/placebo application

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants receive a saline-solution intravenously

Drug: Nacl 0.9%

Ketamine

EXPERIMENTAL

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

Drug: Ketamine

Interventions

Ketamine DRUG

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.

Ketamine

Nacl 0.9% DRUG

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).

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University Hospital, Bonn: lead

Study Sites (1)

Department of Psychiatry and Psychotherapy, University Hospital Bonn

Bonn, 53127, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Psychotic Disorders

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators (except anesthesiologists) are blinded until fMRI data has been preprocessed
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor for Psychiatry

Study Record Dates

• First Submitted: March 14, 2022
• First Posted: April 11, 2022
• Study Start: June 15, 2019
• Primary Completion: September 27, 2020
• Study Completion: September 27, 2020
• Last Updated: April 18, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)