Clinical TrialDepressive DisordersKetamineKetamineCompleted

Examining The Effect Of Ketamine On Glutamate/Glutamine Cycling

Mechanistic interventional study (n=36) using ketamine in healthy and depressed participants to examine glutamate/glutamine cycling and behavioural effects during 13C-MRS.

Target Enrollment
36 participants
Study Type
Phase I interventional
Design
Non-randomized, single Blind

Detailed Description

Randomised status: non-randomised, crossover design for mechanistic/basic-science purposes; 36 actual participants including healthy controls and participants with MDD receiving ketamine during magnetic resonance scans.

Primary outcomes assess ketamine effects on glutamate/glutamine cycling using 13C‑MRS alongside behavioural measures (MADRS, QIDS-SR16) and safety screening; exclusion criteria include active substance dependence, serious medical/neurological illness, pregnancy, and significant suicidality.

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Healthy

experimental

Healthy participants will receive ketamine during the scan.

Interventions

  • Ketamine

    Ketamine administered during scan (dose/route not specified in source).

Depressed

experimental

Participants with major depressive disorder will receive ketamine during the scan.

Interventions

  • Ketamine

    Ketamine administered during scan (dose/route not specified in source).

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion 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.
  • 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-Åsberg 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

  • Healthy Group - 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), or drinking more than 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 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 - 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.
  • First-degree family member with history of schizophrenia or any other psychotic disorder.
  • Serious suicide or homicide risk, as assessed by evaluating clinician (see suicidalityDetails).
  • 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.

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomizedsingle Blind
  • Target Enrollment36 participants
  • Timeline
    Start: 2013-01-07
    End: 2021-06-10
  • Compounds
    KetamineKetamine
  • Topic
    Depressive Disorders

Locations

Yale Depression Research Program — New Haven, Connecticut, United States

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