A Multimodal Neuroimaging Study of Brain Activation Patterns Under Ketamine

Major Depressive Disorder Clinical Trial

Official title:

Brain Activation Patterns Under Emotional and Neurochemic Stimulation With Ketamine: A Multimodal Neuroimaging Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03609190
• Other study ID #: E-31/2008
• Status: Completed
• Phase: Early Phase 1
• Start date: January 2015
• Est. completion date: December 2018

Study information

• Verified date: March 2019
• Source: Psychiatric University Hospital, Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 60 Years

Eligibility

Inclusion Criteria:

• treatment resistant depressive episode

• no restrictions regarding antidepressant medication

Exclusion Criteria:

• 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

• left handedness

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Ketamine
i.v. infusion of 0.25 mg/kg S-ketamine over 40 min
• Placebo
i.v. infusion of NaCl over 40 min

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Psychiatric University Hospital, Zurich

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in functional reactivity to emotional stimuli	fMRI BOLD	Change from baseline to 24h-post infusion
Primary	Change in glutamate concentrations in prefrontal cortex	1H-MRS	Change from baseline to 24h-post infusion
Primary	Change in resting-state functional connectivity	rsfMRI	Change from baseline to 24h-post infusion