A Multimodal Neuroimaging Study of Brain Activation Patterns Under Ketamine

NCT03609190 | Completed Early Phase 1

• 1 other identifier: E-31/2008
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of the project is to establish a multimodal imaging approach for the investigation of the neural mechanisms underlying neuroreceptor regulation, glutamatergic metabolism and brain function that are of particular relevance for major depressive disorder (MDD) and that can be translated into clinical applications. There is growing evidence for imbalance with regard to glutamatergic neurotransmission in stress-related affective disorders. Further support for the hypothesis that dysfunctional glutamatergic signaling underlies major depressive disorder, and indeed that its reversal constitutes a potential efficacious mechanism of action, is provided by the evidence that pharmacological compounds active at the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor such as ketamine exert rapid antidepressant effects. As a tool compound ketamine enables the safe investigation of the brain region-specific effects of NMDA receptor antagonism in terms of glutamatergic neurotransmission, brain function and the association of these neural changes with emotional state, thereby allowing for increased understanding of the therapeutic mechanism of action. The possibility to simultaneously study brain perfusion (arterial spin labeling), functional brain activity (fMRI) and connectivity (resting state fMRI), neurometabolism (proton magnetic resonance spectroscopy) and metabotropic glutamate receptor densities (positron emission tomography) will unravel their functional interplay in the mechanisms underlying the regulation of mood and cognition. Combining those imaging modalities with treatment interventions in healthy subjects and depressed patients, this project aims at providing insight into the neuropharmacological effects of ketamine and its antidepressant properties.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (3)

• Change in functional reactivity to emotional stimuli

  fMRI BOLD

  Change from baseline to 24h-post infusion

• Change in glutamate concentrations in prefrontal cortex

  1H-MRS

  Change from baseline to 24h-post infusion

• Change in resting-state functional connectivity

  rsfMRI

  Change from baseline to 24h-post infusion

Study Arms (2)

Ketamine

EXPERIMENTAL

i.v. infusion of 0.25 mg/kg S-ketamine over 40 min

Drug: Ketamine

Placebo

PLACEBO COMPARATOR

i.v. infusion of NaCl over 40 min

Drug: Placebo

Interventions

Ketamine DRUG

i.v. infusion of 0.25 mg/kg S-ketamine over 40 min

Ketamine

Placebo DRUG

i.v. infusion of NaCl over 40 min

Placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• treatment resistant depressive episode
• no restrictions regarding antidepressant medication

You may not qualify if:

• lifetime antidepressant treatment with ketamine
• lifetime recreational use of ketamine
• cardiovascular diseases such as hypertonia, cardiac insufficiency or myocardial infarct in the past six months
• insufficiently treated anemia
• hyper- or hypothyroidism
• lifetime increased intracranial pressure or glaucoma
• chronic physical diseases
• hepatorenal dysfunction
• any relevant psychiatric or neurological comorbidity, in particular dementia, epileptic seizures (lifetime), schizophrenia (lifetime), psychosis (lifetime), or post-traumatic stress disorder (current).
• acute suicidality
• substance abuse disorders
• recent heart or head surgery
• metallic body implants
• agoraphobia
• pregnancy

Sponsors & Collaborators

• Psychiatric University Hospital, Zurich: lead

Related Publications (2)

• Herrera-Melendez A, Stippl A, Aust S, Scheidegger M, Seifritz E, Heuser-Collier I, Otte C, Bajbouj M, Grimm S, Gartner M. Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine. Eur Neuropsychopharmacol. 2021 Feb;43:63-70. doi: 10.1016/j.euroneuro.2020.11.017. Epub 2020 Dec 11.

  PMID: 33309459 DERIVED

• Gartner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Boker H, Hattenschwiler J, Seifritz E, Grimm S, Scheidegger M. Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26.

  PMID: 30819549 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: August 1, 2018
• Study Start: January 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 20, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share