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

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ClinicalTrials.gov Identifier: NCT02935595
Recruitment Status : Completed
First Posted : October 17, 2016
Results First Posted : August 31, 2020
Last Update Posted : August 31, 2020
Sponsor:
Information provided by (Responsible Party):
Sudhakar Selvaraj, The University of Texas Health Science Center, Houston

Tracking Information
First Submitted Date  ICMJE October 12, 2016
First Posted Date  ICMJE October 17, 2016
Results First Submitted Date  ICMJE August 13, 2020
Results First Posted Date  ICMJE August 31, 2020
Last Update Posted Date August 31, 2020
Actual Study Start Date  ICMJE October 14, 2016
Actual Primary Completion Date August 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2020)
  • Cortical Excitability in the Dorsolateral Prefrontal Cortex (DLPFC) as Assessed by Transcranial Magnetic Stimulation-evoked Activity Detected by Electroencephalography (TMS-EEG) [ Time Frame: Baseline ]
  • Cortical Excitability in DLPFC Using TMS-EEG [ Time Frame: 4 hours ]
  • Cortical Excitability in DLPFC Using TMS-EEG [ Time Frame: 24 hours ]
  • Cortical Excitability in DLPFC Using TMS-EEG [ Time Frame: 7 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
  • Cortical Excitability in DLPFC using TMS-EEG [ Time Frame: Baseline before 1st and 2nd infusion, through study completion, an average of 2 years. ]
  • Cortical Excitability in DLPFC Using TMS-EEG [ Time Frame: 4 hours after 1st and 2nd infusion, through study completion, an average of 2 years. ]
  • Cortical Excitability in DLPFC Using TMS-EEG [ Time Frame: 24 hours after 1st and 2nd infusion, through study completion, an average of 2 years. ]
  • Cortical Excitability in DLPFC Using TMS-EEG [ Time Frame: 7 days after 1st and 2nd infusion, through study completion, an average of 2 years. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2020)
  • Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline ]
    Total MADRS score ranges from 0 to 60, and a higher score indicates more severe depression, as follows: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression
  • Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 4 hours ]
    Total MADRS score ranges from 0 to 60, and a higher score indicates more severe depression, as follows: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression
  • Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 24 hours ]
    Total MADRS score ranges from 0 to 60, and a higher score indicates more severe depression, as follows: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression
  • Safety as Indicated by Number of Adverse Events [ Time Frame: 24 hours ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
  • 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. ]
  • 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. ]
  • 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. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
Official Title  ICMJE A Systematic Investigation of Neurophysiological Correlates of Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Treatment Resistant Depression
Intervention  ICMJE Drug: Ketamine
Ketamine Hydrochloride Injection
Other Name: Ketamine Hydrochloride
Study Arms  ICMJE Experimental: Ketamine
Slow infusions of ketamine will take place over a time period of 40 minutes.
Intervention: Drug: Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 13, 2020)
9
Original Estimated Enrollment  ICMJE
 (submitted: October 14, 2016)
20
Actual Study Completion Date  ICMJE August 16, 2017
Actual Primary Completion Date August 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (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 NCT02935595
Other Study ID Numbers  ICMJE HSC-MS-16-0705
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sudhakar Selvaraj, The University of Texas Health Science Center, Houston
Study Sponsor  ICMJE The University of Texas Health Science Center, Houston
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sudhakar Selvaraj, MBBS, DPhil University of Texas
PRS Account The University of Texas Health Science Center, Houston
Verification Date August 2020

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