Examining The Effect Of Ketamine On Glutamate/Glutamine Cycling

• ClinicalTrials.gov Identifier: NCT02037035
• Recruitment Status: Completed
• First Posted: January 15, 2014
• Last Update Posted: September 8, 2021
• Sponsor: Yale University
• Collaborators: National Institute of Mental Health (NIMH); American Psychiatric Association
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

This study is looking at the mechanisms underlying the behavioral effects of ketamine in healthy and depressed individuals.

Condition or disease	Intervention/treatment	Phase
Depression	Drug: Ketamine	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Examining The Effect Of Ketamine On Glutamate/Glutamine Cycling
• Study Start Date: July 2013
• Actual Primary Completion Date: June 2021
• Actual Study Completion Date: June 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Healthy; Healthy participants will receive ketamine in the scan	Drug: Ketamine
Experimental: Depressed; Depressed participants will receive ketamine in the scan	Drug: Ketamine

Outcome Measures

Primary Outcome Measures :

1. Glutamate Metabolism [ Time Frame: 40-75 minutes ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Healthy Group

Inclusion Criteria:

• Male or female between the ages of 21-65 years.
• Able to provide written informed consent.
• Able to read and write English.

Exclusion Criteria:

• Personal or first-degree family member with history of mood, anxiety, or psychotic axis I DSM-IV disorders confirmed after comprehensive psychiatric evaluation.
• Any history of serious medical or neurological illness.
• Any signs of major medical or neurological illness on examination or as a result of ECG screening or laboratory studies.
• Lifetime history of psychoactive substance or alcohol dependence or substance or alcohol abuse (other than nicotine or caffeine abuse), or drinking more that 5 drinks/week during the last year.
• Abnormality on physical examination.
• A positive pre-study (screening) urine drug screen or, at the study physician's discretion on any drug screens given before the scans.
• Pregnant or lactating women or a positive urine pregnancy test for women of child-bearing potential at screening or prior to any imaging day.
• Subjects who test positive for HIV or viral hepatitis (hepatitis B and/or C)
• Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within the week prior to the MRI scan.
• Any history indicating learning disability, mental retardation, or attention deficit disorder.
• Known sensitivity to ketamine.
• Body circumference of 52 inches or greater.
• Body weight of 280 pounds or greater.
• History of claustrophobia.
• Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire.
• Donation of blood in excess of 500 mL within 56 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Resting blood pressure lower than 90/60 or higher than 150/90,or resting heart rate lower than 45/min or higher than 100/min.

Depression Group

Inclusion Criteria:

• Male or female between the ages of 21-65 years.
• Able to provide written informed consent.
• Current MDD Single Episode (296.2x) or Recurrent (296.3x), as determined by the Structured Clinical Interview for DSM-IV (SCID) patient edition
• Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of first 13C-MRS.
• Quick Inventory of Depressive Symptoms - Self-Report (QIDS-SR16) score of 19 or higher at baseline and start of first 13C-MRS.
• No psychotropic medications for 2 or more weeks (4 weeks for Fluoxetine) prior to first 13C-MRS.
• Be able to understand and speak English.

Exclusion Criteria:

• Patients with a history of DSM-IV-TR diagnosis of bipolar disorder or schizophrenia or schizoaffective disorder or currently exhibiting psychotic features associated with their depression; dementia or suspicion thereof, is also exclusionary.
• First-degree family member with history of schizophrenia or any other psychotic disorder.
• Serious suicide or homicide risk, as assessed by evaluating clinician; A serious suicide risk will be considered an inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death.
• Substance abuse or dependence during the 12 months prior to screening.
• Any history of serious medical or neurological illness.
• Any signs of major medical or neurological illness.
• Abnormality on physical examination. A subject with a clinical abnormality may be included only if the study physician considers the abnormality will not introduce additional risk factors and will not interfere with the study procedure.
• A positive pre-study (screening) urine drug screen or on any drug screens given before the scans.
• Pregnant or lactating women or a positive urine pregnancy test for women of childbearing potential at screening or prior to any imaging day.
• Any history indicating learning disability, or mental retardation.
• Known sensitivity to ketamine.
• Body weight of 280 pounds or greater.
• History of claustrophobia.
• Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire.
• Donation of blood in excess of 500 mL within 56 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Resting blood pressure lower than 90/60 or higher than 150/90,or resting heart rate lower than 45/min or higher than 100/min.

Contacts and Locations

Locations

United States, Connecticut

Yale Depression Research Program

New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Yale University

National Institute of Mental Health (NIMH)

American Psychiatric Association

Investigators

• Principal Investigator: Lynnette Averill, PhD; Yale School of Medicine

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02037035
• Other Study ID Numbers: 1305011972; 1K23MH101498-01 ( U.S. NIH Grant/Contract )
• First Posted: January 15, 2014
• Last Update Posted: September 8, 2021
• Last Verified: September 2021

Additional relevant MeSH terms:

Depression; Behavioral Symptoms; 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