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Biomarkers of Fast Acting Therapies in Major Depression

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ClinicalTrials.gov Identifier: NCT02165449
Recruitment Status : Recruiting
First Posted : June 17, 2014
Last Update Posted : August 28, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Katherine Narr, University of California, Los Angeles

Brief Summary:
The drug Ketamine, available in medical practice since the late 1960s, is currently used for inducing general anesthesia or sedation during medical procedures. When given slowly as an injection into a vein, ketamine is shown to produce a very rapid effect on depression and to improve depressive symptoms within hours to days. By studying patients who receive a ketamine IV infusion, as an add-on treatment for depression, investigators may start to understand how changes in the brain or in gene function relate to getting better over a very short period of time. In this study, the investigators will enroll 60 patients currently ill with major depression selected to receive IV ketamine therapy under medical supervision. To study neurobiological changes relating to symptom improvement, the investigators will use advanced brain scans to measure brain structure, chemistry and function. Blood samples will measure changes in gene regulation and immune system response. Although some people have a rapid antidepressant response to ketamine, others do not respond. Also, antidepressant effects after ketamine usually wear off within days to weeks. We will determine if up to four doses of ketamine delivered two to three times a week may prolong antidepressant response to ketamine therapy. To determine the durability of ketamine treatment for depression, patients will be monitored by phone and via electronic devices twice a week for up to five weeks and will return for a final assessment when their symptoms return. For this trial, brain and blood sample measurements will occur before and after a patient receives their first ketamine infusion. Patients who do not remit after an initial dose of ketamine, will receive up to three additional ketamine treatments. Mood will be measured 24-hours after each subsequent ketamine infusion and brain and blood measurements be repeated at the time of remission or after the fourth ketamine infusion if remission does not occur. Patients will return for a final brain scan and blood sample when their depressive symptoms return or at five weeks if they continue remission. Investigators will able to see how changes brain measurements, gene regulation and immune response relate to improvements and relapse of depressive symptoms with ketamine IV therapy. The ketamine infusion sessions will occur at a special research unit (CTRC) at UCLA.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Ketamine Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Translational Biomarkers of Fast Acting Therapies in Major Depression
Study Start Date : June 2014
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Ketamine Drug: Ketamine
Approved FDA indications for ketamine include use as an adjunct in the induction and maintenance of general anesthesia and for procedural sedation. For general anesthesia, ketamine is given at dosages ranging from 1-2mg/kg and given either as bolus injection or run continuously (0.1 to 0.3mg/kg/min) in conjunction with another anesthetic or sedation agent. In this study, ketamine at a subanesthetic dose of 0.5mg/kg will be diluted in 60cc of normal saline and administered via a slow IV infusion over 40 minutes at each treatment session in patients while undergoing hemodynamic monitoring. When used in this manner, ketamine infusion does not induce general anesthesia or states of unconsciousness, and patients remain fully awake, responsive to commands, and do not lose respiratory drive.




Primary Outcome Measures :
  1. Change in the Hamilton Depression Rating Scale measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions [ Time Frame: up to 2 weeks ]
    Change in mood ratings from the Hamilton Depression Rating Scale

  2. Change in the Hamilton Depression Rating Scale measured between the last ketamine infusion treatment and 5 week follow-up [ Time Frame: 5 weeks ]
    Change in mood ratings from the Hamilton Depression Rating Scale


Secondary Outcome Measures :
  1. Change in gene expression measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions [ Time Frame: up to 2 weeks ]
    Change in gene expression measured from peripheral blood

  2. Change in gene expression measured between the last ketamine infusion treatment and 5 week follow-up [ Time Frame: 5 weeks ]
    Change in gene expression measured from peripheral blood

  3. Change in non-invasive Magnetic Resonance Imaging measures of structural connectivity measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions [ Time Frame: up to 2 weeks ]
    Change in MRI measures of structural connectivity

  4. Change in non-invasive Magnetic Resonance Imaging measures of structural connectivity measured between the last ketamine infusion treatment and at 5 weeks [ Time Frame: 5 weeks ]
    Change in MRI measures of structural connectivity

  5. Change in non-invasive Magnetic Resonance Imaging measures of functional connectivity measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions [ Time Frame: up to 2 weeks ]
    Change in MRI measures of functional connectivity

  6. Change in non-invasive Magnetic Resonance Imaging measures of functional connectivity measured between the last ketamine infusion treatment and at 5 weeks [ Time Frame: 5 weeks ]
    Change in MRI measures of functional connectivity

  7. Change in non-invasive Magnetic Resonance Imaging measures of neurochemistry measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions [ Time Frame: up to 2 weeks ]
    Change in MRI measures of brain metabolite levels

  8. Change in non-invasive Magnetic Resonance Imaging measures of neurochemistry measured between the last ketamine infusion treatment and at 5 weeks [ Time Frame: 5 weeks ]
    Change in MRI measures of brain metabolite levels



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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 to 64 years, inclusive
  • Diagnosis: DSM-IV TR criteria for non-psychotic major depression
  • Hamilton Depression Rating Scale-17 item ≥ 18 or Montgomery Asberg Depression Scale ≥ 20
  • A history of at least one previous major depressive episode prior to the current episode
  • Recurrent Depression - in the current episode, have not responded to at least 2 adequate antidepressant trials (using Antidepressant Treatment History Form criteria)
  • Have been continuously depressed for between 6-12 months
  • Receiving approved monoaminergic antidepressant therapy
  • No changes in antidepressant medication(s) in the past one (1) month
  • Voluntary patient receiving ketamine
  • Capacity to provide informed consent
  • Have no contraindications to an adjunctive trial of ketamine infusion
  • Be under the current care of a treating Psychiatrist
  • If outpatient, a responsible driver available for transportation to and from scanning sessions
  • Live locally, within travelling distance to UCLA
  • Be available to participate for a 5-week research follow-up

Exclusion Criteria:

  • Younger than 18 or older than 64
  • Serious and imminent suicidal or homicidal risk (active suicidal ideations with or without a plan, HAM-D score ≥ 3 on item 3)
  • Mental retardation or other developmental disorder
  • Diagnosis of dementia of any type
  • History of current substance abuse or dependence
  • Psychotic reactions to medications, alcohol or illicit substances in the past
  • Current or past history of psychosis, schizophrenia, bipolar disorder, delusional disorder or other psychotic disorder
  • Treatment with medications with NMDA and NMDAR action
  • Contraindication to ketamine
  • Depression related to serious medical illness (i.e., mood disorder due to general medical condition)
  • History of neurological disorder or other physical disorder (i.e. significant head injury) that could affect brain functioning
  • Serious or unstable medical or neurological condition(s) that in the opinion of the treating physician or PI renders ketamine unsafe to administer
  • Any condition that would contraindicate scanning (metal implants, claustrophobia or a breathing or movement disorder)
  • Pregnancy (as confirmed by positive urine pregnancy test) or planning on becoming pregnant
  • Non-English speaking (due to scales administered)
  • Live outside of the Los Angeles area

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02165449


Contacts
Contact: Katie Patel 310-794-0305 DGCBiomarkerStudy@mednet.ucla.edu
Contact: Katherine Narr, Ph.D. 310-267-5119 DGCBiomarkerStudy@mednet.ucla.edu

Locations
United States, California
Geffen School of Medicine, UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Katherine Narr, Ph.D.    310-267-5119    narr@ucla.edu   
Principal Investigator: Katherine Narr, Ph.D.         
Sponsors and Collaborators
University of California, Los Angeles
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Katherine Narr, Ph.D. Geffen School of Medicine, University of California, Los Angeles (UCLA)

Responsible Party: Katherine Narr, Associate Professor of Neurology, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT02165449     History of Changes
Other Study ID Numbers: HS001796
K24MH102743 ( U.S. NIH Grant/Contract )
U01MH110008 ( U.S. NIH Grant/Contract )
First Posted: June 17, 2014    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Research data without protected health information will be shared according to approved UCLA IRB protocols.

Keywords provided by Katherine Narr, University of California, Los Angeles:
ketamine
major depression
imaging
gene expression

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