Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine

NCT ID: NCT05327699

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-08
• Study Completion Date: 2026-12-31

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.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Major depressive disorder (MDD) Ketamine

Participants randomized to the ketamine arm will receive a single intravenous (IV) infusion of ketamine at 0.5mg/kg through an indwelling catheter over a 40-100min period.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

A single intravenous (IV) infusion of ketamine calculated at 0.5mg/kg through an indwelling catheter over a 40-100min period.

Major depressive disorder (MDD) Placebo

Participants randomized to the placebo arm will receive a single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

A single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period.

Healthy Controls

The subjects in this group will not receive any intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Ketamine

A single intravenous (IV) infusion of ketamine calculated at 0.5mg/kg through an indwelling catheter over a 40-100min period.

Intervention Type: DRUG

Placebo

A single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period.

Intervention Type: OTHER

Other Intervention Names

Ketalar

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Michael Treadway

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Treadway, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Michael Treadway, PhD

Role: CONTACT

ketaminestudy@emory.edu

(404) 727-7541

Facility Contacts

Michael Treadway, PhD

Role: primary

ketaminestudy@emory.edu

404-727-7541

Other Identifiers

R01MH126083-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00003476

Identifier Type: -

Identifier Source: org_study_id