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

NCT05327699 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00003476R01MH126083-01A1
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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).

Conditions

Major Depressive Disorder

Keywords

Neuroscience; Stress response

Outcome Measures

Primary Outcomes (1)

• Change in glutamate concentration in the medial prefrontal cortex (mPFC)

  The glutamate concentration in the mPFC as determined by in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 Tesla (3T) using standard MRS protocols. The levels of glutamate metabolite will be quantified using a custom quantification algorithm for modelling the background noise inherent in NMR (Nuclear Magnetic Resonance) signals. In MDD participants receiving ketamine, acute stress challenges will result in decreased glutamate in mPFC at 24 hrs that will be sustained at 2 weeks.

  Baseline, 24 hours post-infusion, 14 days post-infusion

Other Outcomes (16)

• Change in Apathy Motivation Index (AMI)

  Baseline, 24 hours post-infusion, 14 days post-infusion

• Change in Motivation and Pleasure Scale (MAP-SR)

  Baseline, 24 hours post-infusion, 14 days post-infusion

• Change in Dysfunctional Attitudes Scale - Short Form (DAS-SF)

  Baseline, 24 hours post-infusion, 14 days post-infusion

Study Arms (3)

Major depressive disorder (MDD) Ketamine

EXPERIMENTAL

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.

Drug: Ketamine

Major depressive disorder (MDD) Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Healthy Controls

NO INTERVENTION

The subjects in this group will not receive any intervention.

Interventions

Ketamine DRUG

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

Also known as: Ketalar

Major depressive disorder (MDD) Ketamine

Placebo OTHER

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

Major depressive disorder (MDD) Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Fractures, Stress

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Fractures, Bone; Wounds and Injuries

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michael Treadway, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Treadway, PhD

CONTACT

(404) 727-7541; ketaminestudy@emory.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: April 14, 2022
• Study Start: November 8, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available within 1 year after completion of the grant.
• Access Criteria: Data will be shared via NDAR (National Database for Autism Research). Data will be available within 1 year after completion of the grant. Investigators will need to access data via NDAR.Data can be used for any purpose that NDAR approves.

Locations

US (1)