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

Primary Purpose

Treatment Resistant Depression

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ketamine
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Harris County Psychiatric Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketamine

Arm Description

Slow infusions of ketamine will take place over a time period of 40 minutes.

Outcomes

Primary Outcome Measures

Cortical Excitability in the Dorsolateral Prefrontal Cortex (DLPFC) as Assessed by Transcranial Magnetic Stimulation-evoked Activity Detected by Electroencephalography (TMS-EEG)
Transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) was performed, and electroencephalography (EEG) recording was performed during TMS stimulation. Data is reported as the local mean field amplitude-area under the curve (LMFA-AUC) from a subset of EEG electrodes around the TMS stimulation site.
Cortical Excitability in DLPFC Using TMS-EEG
Transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) was performed, and electroencephalography (EEG) recording was performed during TMS stimulation. Data is reported as the local mean field amplitude-area under the curve (LMFA-AUC) from a subset of EEG electrodes around the TMS stimulation site.
Cortical Excitability in DLPFC Using TMS-EEG
Transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) was performed, and electroencephalography (EEG) recording was performed during TMS stimulation. Data is reported as the local mean field amplitude-area under the curve (LMFA-AUC) from a subset of EEG electrodes around the TMS stimulation site.
Cortical Excitability in DLPFC Using TMS-EEG

Secondary Outcome Measures

Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
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)
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)
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

Full Information

First Posted
October 12, 2016
Last Updated
January 3, 2022
Sponsor
The University of Texas Health Science Center, Houston
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1. Study Identification

Unique Protocol Identification Number
NCT02935595
Brief Title
Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
Acronym
ketamine
Official Title
A Systematic Investigation of Neurophysiological Correlates of Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
October 14, 2016 (Actual)
Primary Completion Date
August 16, 2017 (Actual)
Study Completion Date
August 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ketamine
Arm Type
Experimental
Arm Description
Slow infusions of ketamine will take place over a time period of 40 minutes.
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Ketamine Hydrochloride
Intervention Description
Ketamine Hydrochloride Injection
Primary Outcome Measure Information:
Title
Cortical Excitability in the Dorsolateral Prefrontal Cortex (DLPFC) as Assessed by Transcranial Magnetic Stimulation-evoked Activity Detected by Electroencephalography (TMS-EEG)
Description
Transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) was performed, and electroencephalography (EEG) recording was performed during TMS stimulation. Data is reported as the local mean field amplitude-area under the curve (LMFA-AUC) from a subset of EEG electrodes around the TMS stimulation site.
Time Frame
Baseline
Title
Cortical Excitability in DLPFC Using TMS-EEG
Description
Transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) was performed, and electroencephalography (EEG) recording was performed during TMS stimulation. Data is reported as the local mean field amplitude-area under the curve (LMFA-AUC) from a subset of EEG electrodes around the TMS stimulation site.
Time Frame
4 hours
Title
Cortical Excitability in DLPFC Using TMS-EEG
Description
Transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) was performed, and electroencephalography (EEG) recording was performed during TMS stimulation. Data is reported as the local mean field amplitude-area under the curve (LMFA-AUC) from a subset of EEG electrodes around the TMS stimulation site.
Time Frame
24 hours
Title
Cortical Excitability in DLPFC Using TMS-EEG
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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
Time Frame
Baseline
Title
Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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
Time Frame
4 hours
Title
Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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
Time Frame
24 hours
Title
Safety as Indicated by Number of Adverse Events
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sudhakar Selvaraj, MBBS, DPhil
Organizational Affiliation
University of Texas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Harris County Psychiatric Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77021
Country
United States

12. IPD Sharing Statement

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Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients

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