Trial record 16 of 297 for:    depression NIH

Rapid Antidepressant Effects of Ketamine in Major Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT00088699
First received: July 30, 2004
Last updated: September 15, 2015
Last verified: August 2015
  Purpose

This study examines whether Ketamine can cause a rapid-next day antidepressant effect in patients with Major Depression/Bipolar Disorder .

Purpose: This study will test whether a single dose of ketamine - a drug that blocks a brain receptor called NMDA - can cause a rapid (next day) antidepressant effect in patients with major depression. Several medications are effective for treating depression; however, they take weeks or months to achieve their full effects. A more rapidly acting antidepressant would have a significant impact on the treatment of depression. In a previous study, ketamine produced a rapid antidepressant effect within hours, but the effect lasted less than 1 week. Understanding how ketamine works may lead to a better understanding of the causes of depression and the design of a longer lasting rapidly acting antidepressant.Patients between 18 and 65 years of age who are currently experiencing an episode of major depression of at least 4 weeks duration and have not responded to two treatment trials may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, and blood and urine tests.Participants undergo the following tests and procedures:Medication tapering: Patients who are taking medications for depression are tapered off the drugs over a 1- to 2-week period. Ketamine/placebo trial: Patients are given a single dose of either ketamine or placebo (an inactive substance), administered intravenously (through a vein) over 40 minutes. After 7 days, patients are given another dose of study drug in crossover fashion; that is, those who previously took ketamine are switched to receive placebo, and those who took placebo are switched to ketamine. Oximetry (measurement of blood oxygen), pulse, and blood pressure are measured continuously for 1 hour before and 4 hours after each ketamine or placebo dose to monitor safety. Interviews and rating scales: Patients complete a series of psychiatric rating scales to assess the effects of the study drug on mood and thinking. The rating scales are repeated up to 18 times during the study, with each time taking about 15 to 20 minutes. Physical examination and laboratory tests: Patients have a physical examination, blood tests, weight measure, and electrocardiogram (ECG) at the beginning and end of the study.


Condition Intervention Phase
Depression
Mood Disorders
Bipolar Depression
Major Depresssion
Drug: Ketamine
Drug: Riluzole
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Investigation of the Rapid (Next Day) Antidepressant Effects of an NMDA Antagonist

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Efficacy (reduction from baseline in Montgomery Asberg Depression Rating Scale scores between groups); 2) putative biomarkers of response (task-dependent and resting-state activity in the anterior cingulate cortex (ACC) and the amygdala; [ Time Frame: Ongoing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 3) GABA and Glx/Glutamate ratio; 4) gray matter volume and integrity of white matter fibers connecting the ACC and the amygdala; 4) fMRI task-dependent and resting-state activity changes in the ACC and the amygdala; [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • 5) Correlations between fMRI task-dependent and resting-state activity changes in the ACC and the amygdala; and 6) differential neural effects of ketamine vs. placebo in patients with MDD, BD, and healthy control subjects. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 324
Study Start Date: July 2004
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

General patient inclusion criteria

  1. Male or female subjects, 18 to 65 years of age.
  2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
  3. Subjects must fulfill DSM-IV criteria for Bipolar I or II depressed without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P.
  4. Subjects must have an initial score of at least 20 on the MADRS at screen and at baseline of study phase I.
  5. Subjects must have failed to respond in the past to an adequate dose and duration of at least one antidepressant (SSRI, bupropion, or venlafaxine) during a depressive episode
  6. Current depressive episode of at least 4 weeks duration.

Additional Inclusion Criteria for substudy 2 (patients with MDD)

1. Subjects must take VPA or lithium (valproate 50-125 g/ml or lithium 0.6-1.2 mEq/L) for at least 4 weeks prior to Visit 2 and for the entire duration of the study. If the subject is not taking lithium or VPA, the research physician may start them on lithium or VPA at the NIH.

Additional inclusion criteria for substudy 4 (patients with MDD or BD)

  1. Age of onset less than 40 years of age.
  2. Subjects with MDD must fulfill DSM-IV criteria for Major Depression single episode or recurrent without psychotic features based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P).
  3. Subjects with bipolar disorder must have a YMRS of 12 or less at baseline for Phase I.
  4. A failed adequate trial of ECT would count as an adequate antidepressant trial.
  5. In women of childbearing age, a negative pregnancy test within 24 hours of MRI.

Inclusion criteria for healthy control subjects (Substudy 4 only)

  1. Age 18-65 years.
  2. Written informed consent completed.

EXCLUSION CRITERIA:

General patient exclusion criteria

  1. Current or past diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV.
  2. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months.
  3. Female subjects who are either pregnant or nursing.
  4. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
  5. Subjects with uncorrected hypothyroidism or hyperthyroidism.
  6. Subjects with one or more seizures without a clear and resolved etiology.
  7. Treatment with a reversible MAOI within 4 weeks prior to study phase I.
  8. Treatment with fluoxetine within 5 weeks prior to study phase I.
  9. Treatment with any other concomitant medication not allowed (Appendix A for Substudy 2; Appendix G for Substudy 4) 14 days prior to study phase I.
  10. No structured psychotherapy will be permitted during the study.
  11. Current NIMH employee/staff or their immediate family member.

Additional Exclusion Criteria for substudy 2 (patients with MDD)

1. Previous treatment with ketamine or hypersensitivity to amantadine.

Additional Exclusion Criteria for Substudy 4 (patients with MDD or BD)

  1. Subjects who currently are using drugs (except for caffeine or nicotine), must not have used illicit substances in the 2 weeks prior to screen and must have a negative alcohol and drug urine test (except for prescribed benzodiazepines) urine test at screening.
  2. Presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
  3. Clinically significant abnormal laboratory tests.
  4. For imaging procedures, Presence of metallic (ferromagnetic) implants (e.g, heart pacemaker, aneurysm clip).
  5. Subjects who, in the investigator s judgment, pose a current serious suicidal or homicidal risk, or who have a MADRS item 10 score of > 4.

Exclusion Criteria for healthy control subjects (Substudy 4 only)

  1. Current or past Axis I diagnosis
  2. Presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips).
  3. Presence of medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
  4. Treatment with any of the exclusionary medications detailed in Appendix G 14 days prior to Phase 1 of the Substudy 4.
  5. Current or past alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine).
  6. Presence of psychiatric disorders in first-degree relatives.
  7. Female subjects who are either pregnant or nursing.

7.8.Current NIMH employee/staff or their immediate family member.

  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: NCT00088699

Contacts
Contact: Nancy Brutsche, R.N. (877) 646-3644 moodresearch@mail.nih.gov
Contact: Carlos A Zarate, M.D. (301) 451-0861 zaratec@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Carlos A Zarate, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier: NCT00088699     History of Changes
Other Study ID Numbers: 040222  04-M-0222 
Study First Received: July 30, 2004
Last Updated: September 15, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Depression
NMDA Antagonist
Treatment Resistant
Glutamatergic System
Bipolar Disorder
Major Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Mood Disorders
Behavioral Symptoms
Mental Disorders
Antidepressive Agents
Ketamine
Analgesics
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 02, 2016