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Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients

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ClinicalTrials.gov Identifier: NCT02106325
Recruitment Status : Completed
First Posted : April 8, 2014
Results First Posted : September 14, 2018
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date  ICMJE December 12, 2013
First Posted Date  ICMJE April 8, 2014
Results First Submitted Date  ICMJE June 19, 2017
Results First Posted Date  ICMJE September 14, 2018
Last Update Posted Date September 14, 2018
Study Start Date  ICMJE December 2013
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Evaluate the Effects of Ketamine on Depressive Symptomatology by Measuring Change in Score on the Montgomery-Asberg Depressive Rating Scale [ Time Frame: Baseline and 16 weeks ]
    40 Minutes Post Infusion, The MADRS-S instrument has nine questions, with an overall score ranging from 0 to 54 points. 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
  • Beck Depression Inventory-II (BDI-II) [ Time Frame: 120 min post-infusion ]
    BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. 0-13 Indicates minimal depression 14-19 Indicates mild depression 20-28 Indicates Moderate depression 29-63 Indicates Severe depression
  • Hamilton Depression Scale (Ham-D) [ Time Frame: 4-6 hours post-infusion ]
    Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Sum the scores from the first 17 items 0-7= Normal 8-13= Mild Depression 14-18= Moderate Depression 19-22= Severe Depression >23= Very Severe Depression
Original Primary Outcome Measures  ICMJE
 (submitted: April 3, 2014)
Evaluate the effects of ketamine on depressive symptomatology [ Time Frame: 0-16 weeks ]
Montgomery-Asberg Depressive Rating Scale
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Change in Treatment Alliance Score [ Time Frame: Baseline and 16 weeks ]
    The I-TAS is a 10-item, Likert-style rating scale designed to assess a patient's composite treatment alliance as it develops across multi-disciplinary treatment components. The I-TAS was intended to measure the primary alliance factors identified by Hatcher and Barends (1996) of bond, goals and collaboration. Each question is scored on a scale of 0 (Completely False) to 6 (Completely True). Total scores on the ITAS range from 0 to 60, with higher scores representing greater alliance with the treatment team (better outcome). The reported score is an average of each participant's total score on the ITAS.
  • Beck Scale for Suicidal Ideation (BSSI) [ Time Frame: 40 minutes post-infusion ]
    BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. 0-13 Indicates minimal depression 14-19 Indicates mild depression 20-28 Indicates Moderate depression 29-63 Indicates Severe depression
  • Montgomery-Åsberg Depression Rating Scale Suicide Ideation Item (MADRS-SI) [ Time Frame: 40 minutes post-infusion ]
    40 Minutes Post Infusion, The MADRS-S instrument has nine questions, with an overall score ranging from 0 to 54 points. 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
  • Length of Inpatient Stay [ Time Frame: 2 Weeks Post-infusion ]
  • Outpatient Follow-up Compliance [ Time Frame: 1 Day ]
    Scoring System: 0= not compliant, 1=compliant
  • Inpatient Treatment Alliance Scale (ITAS) [ Time Frame: 7 days post-infusion ]
    The I-TAS is a 10-item, Likert-style rating scale designed to assess a patient's composite treatment alliance as it develops across multi-disciplinary treatment components. The I-TAS was intended to measure the primary alliance factors identified by Hatcher and Barends (1996) of bond, goals and collaboration. Each question is scored on a scale of 0 (Completely False) to 6 (Completely True). Total scores on the ITAS range from 0 to 60, with higher scores representing greater alliance with the treatment team (better outcome). The reported score is an average of each participant's total score on the ITAS.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2014)
  • Evalaute the effects of ketamine on treatment alliance [ Time Frame: 0-16 weeks ]
    Inpatient Treatment Alliance Scale
  • Evalaute the effects of ketamine on suicidal ideation [ Time Frame: 0-16 weeks ]
    Implicit Association Test
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients
Official Title  ICMJE A Randomized, Double-Blinded Controlled Trial of an N-Methyl D-Aspartate Antagonist as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients
Brief Summary Investigators will conduct a trial to evaluate the use of Ketamine as an alternate treatment for people with Major Depressive Disorder. This study plans to explore the potential that Ketamine's rapid antidepressant action holds for improving outcomes in patients presenting to the Emergency Department with severe depression. Since this is a controlled trial we will use an IV of Ketamine or and equivalent volume of Diphenhydramine. Subjects will be randomly assigned to receive Ketamine or Benadryl. Investigators will then compare measures of mood pre- and post-infusion in the Emergency Department. To supplement self-reported measures of depressive symptoms(e.g. mood), investigators will obtain objective measures of the biological aspects of Major Depressive Disorder.
Detailed Description

To explore the use of ketamine as a potential rapidly-acting antidepressant (RAA) for Emergency Department (ED) patients with major depressive disorder (MDD).

Investigators will conduct a randomized controlled study to evaluate the rapidity and persistence of antidepressant effects of a single sub-anesthetic dose of intravenous (IV) ketamine (0.25mg/kg) or an equivalent volume of diphenhydramine (25mg) delivered IV over 1-2 minutes, by comparing measures of mood pre- and post-infusion in Emergency Department (ED) patients with MDD. Subjects will be randomly assigned (1:1) to receive a bolus of ketamine or diphenhydramine. To supplement self-reported measures of depressive symptoms (e.g., mood, suicidal ideation, etc.), investigators will obtain objective measures of heart rate and heart rate variability, measure serum levels of the pro- and anti-inflammatory cytokines (interleukin IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and tissue necrosis factor, TNF-α), which have been shown to play an important role in stress, depression and suicidal behavior. In addition, investigators will obtain serum levels of brain derived neurotrophic factor (BDNF) because reduced serum BDNF has been described during acute depressive episodes in patients with MDD, with reports of rescue effects following treatment with various antidepressants and with ketamine (Aydemir 2005, Gervasoni 2005, Karege 2002, Karege 2005, Duncan 2013, Shimizu 2003). Investigators will also measure serum magnesium levels, as these have been shown to correlate in a predictive manner with response to conventional antidepressants (Camardese 2012), and there are data to suggest that ketamine's efficacy in treatment-resistant depression could be related to a relative magnesium deficiency in such patients (Murck 2013).

This study will allow investigators to determine to what extent low-dose ketamine, an N-Methyl-D-Aspartate (NMDA) antagonist, achieves a rapid reduction in symptoms for severely depressed ED patients with or without suicidal ideation. For decades, much higher doses of IV ketamine (1-2mg/kg) have been used routinely in the ED as a dissociative anesthetic (Green 2011). In 2011, an open-label study was the first published of the use of low dose ketamine (0.2mg/kg), administered by rapid intravenous infusion, in the ED setting for acutely depressed patients which demonstrated its feasibility, safety, preliminary efficacy and acceptability to both ED patients and staff (Larkin 2011). One long-term goal of this research is to expand treatment options available to depressed ED patients that mitigate the need for inpatient admission and serve as a safety bridge to future out-patient treatment for major depression. As an adjunct to standard treatment, low-dose NMDA receptor antagonists have the potential to positively impact: ED waiting times; repeat visits to the ED; short-term risk of suicide attempts; length of stay on inpatient units and the need for hospital admissions for many acutely depressed patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Depression
Intervention  ICMJE
  • Drug: Ketamine
    IV of Ketamine (.25mg/kg)
    Other Name: Other names for ketamine: ketalar
  • Drug: Diphenhydramine
    Intravenous Diphenhydramine (25mg) at the time of presentation to Emergency Department
    Other Name: Other names for diphenhydramine: benadryl
Study Arms  ICMJE
  • Experimental: Ketamine
    IV Ketamine .25mg/kg
    Intervention: Drug: Ketamine
  • Placebo Comparator: Diphenhydramine
    25mg Diphenhydramine
    Intervention: Drug: Diphenhydramine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 16, 2018)
21
Original Estimated Enrollment  ICMJE
 (submitted: April 3, 2014)
100
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Medically stable as determined by the medical physician
  • Meets criteria for Major Depressive Disorder (MDD) based on a structured clinical Interview (MINI International Neuropsychiatric Interview).
  • Reports symptoms of severe depression at the time of presentation, defined as a score of 24 or greater on the MADRS.
  • Patients for whom a psychiatric evaluation and disposition decision has been made by emergency psychiatry staff to admit to an inpatient psychiatric unit at Bellevue Hospital Center or NYU Tisch Hospital.
  • Each subject must have a level of understanding sufficient to sign an informed consent stating that the treatment being offered is not FDA approved for the treatment of depression and is being provided as an off-label option.

Exclusion Criteria:

  • Pregnancy
  • Inability to read or understand English
  • Current clinical signs of intoxication or delirium at time of study intervention
  • Overdose, within previous 24 hours, of any agent which would impair ketamine metabolism
  • Lifetime misuse/abuse of ketamine, phencyclidine (PCP),or related substances
  • Lifetime history of psychotic spectrum illness
  • First-degree relative with history of psychotic illness
  • Lifetime diagnosis of borderline personality disorder, or as confirmed by assessment using items #90-104 of the SCID-II (for DSM-IV).
  • Subjects with clinically significant abnormal findings as determined by medical history, physical examination, vital signs (blood pressure, heart rate, and respiration rate), O2 saturation measure, 12-lead ECG, clinical laboratory tests (CBC, chemistry panel, thyroid function tests), urine drug screen, and urine pregnancy test (for females of childbearing potential only).
  • Clinically unstable medical, surgical or neurological conditions at ED presentation
  • History of stroke or intracranial hypertension
  • History of glaucoma
  • Subjects with one or more seizures without a clear and resolved etiology
  • Current NMDA antagonist medications (eg. Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan)
  • Known hypersensitivity to ketamine or amantadine
  • Anti-psychotic medications (Typicals or Atypicals), with the exception of low-dose quetiapine (total daily dose of 100mg or less).
  • Actively trying to commit suicide, even in a hospital setting
  • Current homicide risk
  • Unable or unwilling to give informed consent according to HIC guidelines
  • Unable or unwilling to provide 2 contact phone numbers or be followed up per study protocol.
  • Previous enrollment in this study.
  • Concurrent enrollment in a research protocol investigating experimental pharmacologic treatments for depression at this or any other institution.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02106325
Other Study ID Numbers  ICMJE 13-00794
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NYU Langone Health
Study Sponsor  ICMJE NYU Langone Health
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stephen Ross, MD NYU Langone Health
Study Chair: K. Casey Paleos, MD New York Unversity School of Medicine
PRS Account NYU Langone Health
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP