Optimization of IV Ketamine for Treatment Resistant Depression

This study has been completed.
Sponsor:
Collaborator:
Mount Sinai School of Medicine
Information provided by (Responsible Party):
Sanjay Johan Mathew, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00768430
First received: October 7, 2008
Last updated: December 27, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder (MDD)
Treatment Resistant Depression (TRD)
Drug: Ketamine
Drug: Midazolam
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Optimization of Intravenous Ketamine for Treatment-Resistant Depression: A Randomized, Placebo-Controlled, Triple-masked, Clinical Trial

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • MADRS [ Time Frame: 24 hours post-infusion ] [ Designated as safety issue: No ]
    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.


Enrollment: 73
Study Start Date: November 2008
Study Completion Date: November 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Ketamine
Drug: Ketamine
Single dose .5 mg/kg IV (in the vein) infused over 40 minutes
Other Name: Racemic ketamine hydrochloride
Active Comparator: 2
Midazolam
Drug: Midazolam
single dose 0.045 mg/kg IV infused over 40 minutes

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768430

Locations
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Texas
Michael E. Dabakey VA Medical Center & Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Mount Sinai School of Medicine
Investigators
Principal Investigator: Sanjay J. Mathew, MD Baylor College of Medicine
Principal Investigator: Dan V Iosifescu, MD,M.Sc. Mount Sinai School of Medicine
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanjay Johan Mathew, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00768430     History of Changes
Other Study ID Numbers: GCO 07-0114
Study First Received: October 7, 2008
Results First Received: September 5, 2013
Last Updated: December 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Ketamine
Midazolam
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Hypnotics and Sedatives
GABA Modulators

ClinicalTrials.gov processed this record on July 22, 2014