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

Tracking Information

• First Submitted Date: November 19, 2013
• First Posted Date: January 15, 2014
• Last Update Posted Date: September 8, 2021
• Study Start Date: July 2013
• Actual Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 14, 2014): Glutamate Metabolism [ Time Frame: 40-75 minutes ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Examining The Effect Of Ketamine On Glutamate/Glutamine Cycling
• Official Title: Examining The Effect Of Ketamine On Glutamate/Glutamine Cycling
• Brief Summary: This study is looking at the mechanisms underlying the behavioral effects of ketamine in healthy and depressed individuals.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: Single (Participant); Primary Purpose: Basic Science
• Condition: Depression
• Intervention: Drug: Ketamine

Study Arms

• Experimental: Healthy
  Healthy participants will receive ketamine in the scan
  Intervention: Drug: Ketamine
• Experimental: Depressed
  Depressed participants will receive ketamine in the scan
  Intervention: Drug: Ketamine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 14, 2014): 36
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 2021
• Actual Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02037035
• Other Study ID Numbers: 1305011972; 1K23MH101498-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Yale University
• Original Responsible Party: Chadi Abdallah, Yale University, Assistant Professor
• Current Study Sponsor: Yale University
• Original Study Sponsor: Same as current

Collaborators

• National Institute of Mental Health (NIMH)
• American Psychiatric Association

Investigators

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

• PRS Account: Yale University
• Verification Date: September 2021