Ketamine-Induced Psychotic DisorderPhase 4METAKETAIINCT05320991
Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers
A Phase 4 study testing Ketamine and Nacl 0.9% in people with Ketamine-Induced Psychotic Disorder and Social Cognition, run by University Hospital, Bonn at 1 site in Germany.
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… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Ketamine-Induced Psychotic Disorder, Social Cognition, Theory of Mind
- What is being tested?
- Ketamine and Nacl 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteGermany
- Study dates
- 15 Jun 2019to 27 Sep 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Psychiatry and Psychotherapy, University Hospital Bonn
Bonn, 53127
About this study
Official title: A Randomized Control Trial Employing fMRI to Investigate the Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers
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.
- Being tested
- Ketamine, Nacl 0.9%
- Keywords
- ketamine, fMRI, psychosis, mentalizing, social cognition, metacognition
- Medical subject headings
- Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
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%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).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants receive a saline-solution intravenously Receives: 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) Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: During ketamine/placebo application in MRI
Secondary outcomes (2)
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.
Measured: 10 minutes after cessation of MRI and ketamine/placebo application
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
Measured: 20 minutes after cessation of MRI and ketamine/placebo application
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2022
- Study start15 Jun 2019
- Primary completion27 Sep 2020
- Study completion27 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ketamine-Induced Psychotic DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bonn
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rene Hurlemann, University Hospital, Bonn
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05320991
- Sponsor's protocol ID
- #19-03-29 (METAKETA)
- Acronym
- METAKETAII
- Status last verified
- Apr 2022
- First submitted
- 14 Mar 2022
- Last updated
- 18 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Control Trial Employing fMRI to Investigate the Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05320991
- Acronym / sponsor ID
- METAKETAII / #19-03-29 (METAKETA)
- Keywords
- ketamine, fMRI, psychosis, mentalizing, social cognition, metacognition
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University Hospital, BonnUniversity, hospital or other
- Study start
- 15 Jun 2019 (actual)
- Primary completion
- 27 Sep 2020 (actual)
- Study completion
- 27 Sep 2020 (actual)
- First posted
- 11 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Nacl 0.9%Participants receive a saline-solution intravenously |
| Ketamine | Experimental | Drug: KetamineParticipants receive ketamine (Plasma-level 100 ng/ml with an initial bolus administered as a 2 mg/ml solution) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineKetamine 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 | Ketamine |
| 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). | Drug | Placebo |
Primary outcome
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
2 secondary outcomes
Psychotic symptom load in PANSS-Questionnaire
Time frame: 10 minutes after cessation of MRI and ketamine/placebo application
Metacognitive-Questionnaire (MCQ)
Time frame: 20 minutes after cessation of MRI and ketamine/placebo application
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2022.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine and Nacl 0.9% in people with Ketamine-Induced Psychotic Disorder and Social Cognition, run by University Hospital, Bonn at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Mentalizing/Theory of Mind (time frame: During ketamine/placebo application in MRI). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2022.