A Multimodal Neuroimaging Study of Brain Activation Patterns Under Ketamine
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| ClinicalTrials.gov Identifier: NCT03609190 |
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Recruitment Status :
Completed
First Posted : August 1, 2018
Last Update Posted : March 20, 2019
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Major Depressive Disorder | Drug: Ketamine Drug: Placebo | Early Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 10 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Basic Science |
| Official Title: | Brain Activation Patterns Under Emotional and Neurochemic Stimulation With Ketamine: A Multimodal Neuroimaging Study |
| Actual Study Start Date : | January 2015 |
| Actual Primary Completion Date : | December 2018 |
| Actual Study Completion Date : | December 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ketamine
i.v. infusion of 0.25 mg/kg S-ketamine over 40 min
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Drug: Ketamine
i.v. infusion of 0.25 mg/kg S-ketamine over 40 min |
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Placebo Comparator: Placebo
i.v. infusion of NaCl over 40 min
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Drug: Placebo
i.v. infusion of NaCl over 40 min |
- Change in functional reactivity to emotional stimuli [ Time Frame: Change from baseline to 24h-post infusion ]fMRI BOLD
- Change in glutamate concentrations in prefrontal cortex [ Time Frame: Change from baseline to 24h-post infusion ]1H-MRS
- Change in resting-state functional connectivity [ Time Frame: Change from baseline to 24h-post infusion ]rsfMRI
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| Ages Eligible for Study: | 20 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
| Responsible Party: | Milan Scheidegger, Principal Investigator, Psychiatric University Hospital, Zurich |
| ClinicalTrials.gov Identifier: | NCT03609190 |
| Other Study ID Numbers: |
E-31/2008 |
| First Posted: | August 1, 2018 Key Record Dates |
| Last Update Posted: | March 20, 2019 |
| Last Verified: | March 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Depressive Disorder Depressive Disorder, Major Mood Disorders Mental Disorders Ketamine Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
Anesthetics, Dissociative Anesthetics, Intravenous Anesthetics, General Anesthetics Central Nervous System Depressants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action |