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Optimization of IV Ketamine for Treatment Resistant Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00768430
Recruitment Status : Completed
First Posted : October 8, 2008
Results First Posted : January 31, 2014
Last Update Posted : January 31, 2014
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Sanjay Johan Mathew, Baylor College of Medicine

Tracking Information
First Submitted Date  ICMJE October 7, 2008
First Posted Date  ICMJE October 8, 2008
Results First Submitted Date  ICMJE September 5, 2013
Results First Posted Date  ICMJE January 31, 2014
Last Update Posted Date January 31, 2014
Study Start Date  ICMJE November 2008
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 27, 2013)
MADRS [ Time Frame: 24 hours post-infusion ]
Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression.
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2008)
MADRS [ Time Frame: 40 minutes, 120 minutes, 24 hours, 7 days ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Optimization of IV Ketamine for Treatment Resistant Depression
Official Title  ICMJE Optimization of Intravenous Ketamine for Treatment-Resistant Depression: A Randomized, Placebo-Controlled, Triple-masked, Clinical Trial
Brief Summary

Existing treatments for major depressive disorder (MDD) generally take weeks to months to exert their maximal benefit. There is an urgent need to develop rapid-acting treatments for MDD. Ketamine, a high-affinity N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been used as a standard intravenous (IV) anesthetic agent for many years in both pediatric and adult patients. Beyond its well-established role in anesthesia and pain management, there is emerging evidence that ketamine may have rapid antidepressant properties for patients with severe mood disorders.

In this study we are investigating whether ketamine can have an antidepressant effect compared to midazolam. Midazolam has similar anesthetic effects compared to ketamine but has not been shown to be an antidepressant, and is therefore acting as an active control in this study.

The study period can last up to 8 weeks, depending on your response to the study medication. There are two required overnight stays in our Research Commons as part of this study.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Major Depressive Disorder (MDD)
  • Treatment Resistant Depression (TRD)
Intervention  ICMJE
  • Drug: Ketamine
    Single dose .5 mg/kg IV (in the vein) infused over 40 minutes
    Other Name: Racemic ketamine hydrochloride
  • Drug: Midazolam
    single dose 0.045 mg/kg IV infused over 40 minutes
Study Arms  ICMJE
  • Experimental: 1
    Intervention: Drug: Ketamine
  • Active Comparator: 2
    Intervention: Drug: Midazolam
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 8, 2013)
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2008)
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female patients, 21-80 years of age;
  2. Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum beta-human growth hormone at screening and at pre-infusion;
  3. Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
  4. Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
  5. Participants have not responded to three or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
  6. Participant scores on the IDS-C30 must be greater than or equal to 32 at both Screening and within 24 hours prior to Visit 1a (Phase 1);
  7. Current major depressive episode is of at least 4 weeks duration.
  8. Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
  9. Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.

Exclusion Criteria:

  1. Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder
  2. Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
  3. Current diagnosis of Obsessive Compulsive Disorder or eating disorder (bulimia nervosa or anorexia nervosa);
  4. Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
  5. Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
  6. Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
  7. Women who are either pregnant or nursing;
  8. Serious, unstable medical illnesses including hepatic, renal, gastroenterologic (including gastroesophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
  9. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
  10. Patients with one or more seizures without a clear and resolved etiology;
  11. Patients starting hormonal treatment (e.g., estrogen) in the last 3 months prior to Visit 1a;
  12. Treatment with an irreversible MAOI or any other FDA approved Anti depressant medication within one week prior to Visit 1a (with the exception of a stable dose of non-benzodiazepines hypnotics i.e. zolpidem, eszopiclone, etc for at least 3 months);
  13. Treatment with fluoxetine within 4 weeks prior to Visit 1a;
  14. Evidence-based individual psychotherapy (e.g. CBT or IPT) and other non-pharmacological antidepressant treatments (e.g. light therapy) will not be permitted during the acute study period (7 day);
  15. Previous recreational use of PCP or Ketamine.
  16. Past intolerance or hypersensitivity to midazolam
  17. Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by diuretic or beta-blocker therapy alone or in combination.
  18. Evidence of age-related cognitive decline or mild dementia suggested by a score of < 27 on the Mini-Mental State Examination (MMSE) at Screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 80 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 NCT00768430
Other Study ID Numbers  ICMJE GCO 07-0114
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Sanjay Johan Mathew, Baylor College of Medicine
Original Responsible Party Sanjay Mathew, MD, Mount Sinai School of Medicine
Current Study Sponsor  ICMJE Baylor College of Medicine
Original Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE Icahn School of Medicine at Mount Sinai
Investigators  ICMJE
Principal Investigator: Sanjay J. Mathew, MD Baylor College of Medicine
Principal Investigator: Dan V Iosifescu, MD,M.Sc. Icahn School of Medicine at Mount Sinai
PRS Account Baylor College of Medicine
Verification Date December 2013

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