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Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients (ketamine)

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ClinicalTrials.gov Identifier: NCT02935595
Recruitment Status : Active, not recruiting
First Posted : October 17, 2016
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
Sudhakar Selvaraj, The University of Texas Health Science Center, Houston

Brief Summary:
The primary goal of the project is to study the effect of Ketamine on cortical neurophysiological function in TRD patients. The proposal employs robust and non-invasive neurophysiological techniques TMS and EEG to investigate the cortical excitability and oscillatory activity in patients with treatment resistant depression.

Condition or disease Intervention/treatment Phase
Treatment Resistant Depression Drug: Ketamine Phase 2

Detailed Description:

The primary goal of the project is to study the effect of Ketamine on cortical neurophysiological function in Treatment Resistant Depression(TRD) patients. There are three key preclinical findings regarding Ketamine antidepressant effects that motivate the current study: a) low dose Ketamine causes early increase in glutamate neurotransmission; b) Ketamine initiates synaptic plasticity; c) ketamine infusion leads to rapid improvement in depression symptoms. The proposal essentially employs robust and non-invasive neurophysiological techniques, Auditory Steady State Response(ASSR)-gamma oscillatory response and Transcranial Magnetic Stimulation(TMS) cortical excitability to investigate the above findings in patients with treatment resistant depression.

Study:

Ketamine Infusion:

We will employ an open-label study in which the infusion session, the enrolled TRD patients will receive low dose Ketamine (0.5 mg/kg) over 40 minutes.

Cortical Excitability:

TMS stimulation will be applied to the corresponding region of the contralateral primary motor cortex to determine motor threshold and to examine the motor cortical excitability measures after Ketamine. The optimal coil position will be determined by moving the TMS coil in 1-cm increments over the motor cortical area while delivering single or paired magnetic pulses and by observing maximal contraction of the contralateral abductor pollicis brevis (APB). Electromyography readings will be obtained from the APB muscle. TMS stimulation will then be applied to Left DLPFC or Left Brodmann Area 6 to investigate cortical excitability changes after ketamine. Electroencephalography(EEG) recordings will be concurrent with TMS procedure.

ASSR/EEG paradigm:

Participants may engage in the auditory steady state response task where click trains of 500-ms duration will be presented binaurally at 65 ± 5 decibel(dB). The click train repetition frequencies will be 40 Hz and presented in the context of an auditory oddball paradigm to ensure participant attention to the stimuli. This task will be done while participants undergo EEG recordings.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Systematic Investigation of Neurophysiological Correlates of Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
Study Start Date : September 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketamine
Slow infusions of ketamine will take place over a time period of 40 minutes.
Drug: Ketamine
Ketamine Hydrochloride Injection
Other Name: Ketamine Hydrochloride




Primary Outcome Measures :
  1. Cortical Excitability in DLPFC using TMS-EEG [ Time Frame: Baseline before 1st and 2nd infusion, through study completion, an average of 2 years. ]
  2. Cortical Excitability in DLPFC using TMS-EEG [ Time Frame: 4 hours after 1st and 2nd infusion, through study completion, an average of 2 years. ]
  3. Cortical Excitability in DLPFC using TMS-EEG [ Time Frame: 24 hours after 1st and 2nd infusion, through study completion, an average of 2 years. ]
  4. Cortical Excitability in DLPFC using TMS-EEG [ Time Frame: 7 days after 1st and 2nd infusion, through study completion, an average of 2 years. ]

Secondary Outcome Measures :
  1. Reduction in severity of depressive symptoms will be measured using the Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline, through study completion, an average of 2 years. ]
  2. Reduction in severity of depressive symptoms will be measured using the Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: upto 1 day after 1st and 2nd Infusion, through study completion, an average of 2 years. ]
  3. Safety as indicated by number of adverse events [ Time Frame: Up to 7 days after Ketamine infusion, through study completion, an average of 2 years. ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be between 18-60 years of age
  • Meet criteria for Treatment Resistant Depression (defined as two or more unsuccessful trials of antidepressants at an adequate dose for at least 4 weeks)

Exclusion Criteria:

  • Diagnosed with intellectual disability, eg. Mental retardation, neurodegenerative diseases, eg. Early onset neurocognitive disturbances such as frontotemporal dementia or behavioral disorders, eg. adult onset Attention Deficit Hyperactivity Disorder,
  • Diagnosed with Bipolar Disorder (BD),
  • Diagnosed with personality disorders,
  • Previously or currently diagnosed with psychosis (schizoaffective disorder -SAD) or schizophrenia - SCZ),
  • Current major medical problems that affect brain anatomy, neurochemistry, or function, e.g., obstructive sleep apnea requiring Continuous Positive Airway Pressure (CPAP), liver insufficiency, kidney insufficiency, cardiovascular problems, systemic infections, cancer, auto-immune diseases, and any brain disorder (seizure disorder, stroke, dementia, degenerative neurologic diseases); history of any brain diseases, including seizures, stroke, meningitis, encephalitis, dementia, degenerative brain diseases, and head injury with loss of consciousness for any period of time,
  • Diagnosed specifically with a cardiovascular disorders such as Hypertension, Arrhythmias, Chronic Heart Failure, Myocardial Infarction (MI) or suffering from Chronic Obstructive Pulmonary Disease (COPD) or asthma. Cardiac clearance prior to enrolling in the study and medical records from physician will be required per patient's Primary Care Physician.
  • Patients with increased risk of laryngospasm, active upper respiratory infections, respiratory depression, increased intracranial pressure, thyroid disease, or porphyria,
  • Current substance abuse or dependence. Only patients who achieved stable, full remission for at least 6 months will be included
  • Pregnancy or Breast feeding. All female in reproductive age will undergo pregnancy tests. Female participants will be required to provide evidence of use of contraceptives during the course of the study,
  • Unable to understand the design and requirements of the study.
  • Unable to sign the informed consent for any reason.

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): NCT02935595


Locations
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United States, Texas
Harris County Psychiatric Center
Houston, Texas, United States, 77021
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
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Principal Investigator: Sudhakar Selvaraj, MBBS, DPhil University of Texas

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Responsible Party: Sudhakar Selvaraj, MBBS., DPhil (Oxon)., MRCPsych, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02935595     History of Changes
Other Study ID Numbers: HSC-MS-16-0705
First Posted: October 17, 2016    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
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