Clinical trial NCT05327699: Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine
Official title: Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Major Depressive Disorder
Keywords: Neuroscience
Stress response
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-04-14
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The main purpose of this study is to investigate the effects of ketamine on decision-making and emotion processing in a sample of individuals diagnosed with Major Depressive Disorder (MDD).

Detailed description: The main purpose of this study is to understand the effects of sub-anesthetic ketamine doses on varying functional domains of depression such as anhedonia, decision-making, and emotion processing in subjects diagnosed with Major Depressive Disorder (MDD). The study will evaluate these effects using a combination of questionnaires, neuroimaging techniques, and behavioral tasks. The clinical trial portion will only include subjects with MDD (Major Depressive Disorder). A separate group of healthy controls, n=60, will be invited to only complete a behavioral/interview session and one neuroimaging session.The healthy controls group will not be randomized nor receive any study intervention and will only serve to collect performance baseline measures. The primary aims of this study are to evaluate 1) the glutamate stress response in MDD patients and matched controls by whole-brain imaging, 2) the multi-modal associations between glutamate stress response and neuroimaging and behavioral assessments of motivation and valuation, and 3) the effect of ketamine versus placebo on glutamate stress response in MDD subjects.

Eligibility criteria: Inclusion Criteria:

MDD Patients:

* willing and able to give written informed consent
* men or women, 18-65 years of age
* primary diagnosis of DSM-V MDD, current, as diagnosed by the SCID-I
* score of ≥20 on the Beck Depression Inventory, which will include patients characterized as having "moderate/severe" (20-28) or "very-severe" (29-63) depressive symptoms
* off all antidepressant therapy for at least 8 weeks prior to the baseline visit

Healthy Controls:

* willing and able to give written informed consent
* men or women, 18-65 years of age

Exclusion Criteria:

MDD Patients:

* history of any bipolar disorder or psychotic disorder
* active psychotic symptoms of any type
* substance abuse/dependence within 6 months of study entry (as determined by SCID)
* unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing), including upper respiratory disease or asthma, glaucoma or porphyria.
* active suicidal ideation as determined by a score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSR)
* use of any recreational drugs as confirmed by urine drug screen at the time of scanning
* pregnancy or lactation
* use of glucocorticoids at any time during the study
* Raynaud's disease that may interfere with the cold-pressor
* contraindications for MRI
* MMSE score \<28
* elevated blood pressure prior to infusion (systolic \> 160 or diastolic \>100)
* history of treatment resistance as determined by ATRQ
* prior adverse reaction to ketamine
* use of antipsychotic medications
* use of greater than 2mg daily of lorazepam or similar benzodiazipine.
* Regular smoker as self-reported

Healthy Controls:

* evidence of any psychiatric disorder with exception of specific phobia, and no history of any psychiatric disorder except mild past substance use disorder as diagnosed by the SCID-I
* history of any substance abuse within the last 6 months
* use of any recreational drugs as confirmed by urine drug screen at the time of scanning
* pregnancy or lactation
* use of glucocorticoids at any time during the study
* Raynaud's disease that may interfere with the cold-pressor
* contraindications for MRI
* MMSE score \<28
* Regular smoker as self-reported

Primary outcomes:
measure: Change in glutamate concentration in the medial prefrontal cortex (mPFC)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
Secondary outcomes:
Other outcomes:
measure: Change in Apathy Motivation Index (AMI)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Motivation and Pleasure Scale (MAP-SR)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Dysfunctional Attitudes Scale - Short Form (DAS-SF)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Perceived Stress Scale (PSS)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in State-Trait Anxiety Inventory (STAI)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Mini-Mental State Exam (MMSE)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Reaction Time Task (RTT)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Reinforcement Learning Task
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Apathy Evaluation Scale (AES)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in UCLA Loneliness Scale
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Digit Symbol Task (DST)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Finger Tapping Task (FTT)
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Effort-Based Decision-Making Task
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in Effort-Discounting Task
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in MoVER Task - Navigate
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
measure: Change in MoVER Task- Passive Viewing
timeFrame: Baseline, 24 hours post-infusion, 14 days post-infusion
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Michael Treadway, PhD
role: PRINCIPAL_INVESTIGATOR
References: