Treatment Resistant DepressionPhase 2ketamineNCT02935595
Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
A Phase 2 study testing Ketamine in people with Treatment Resistant Depression, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Oct 2016to 16 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Harris County Psychiatric Center
Houston, Texas, 77021
About this study
Official title: A Systematic Investigation of Neurophysiological Correlates of Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
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.
Read the 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.
- Conditions
- Treatment Resistant Depression
- Being tested
- Ketamine
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketamine Hydrochloride
Ketamine Hydrochloride Injection
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Slow infusions of ketamine will take place over a time period of 40 minutes. Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
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.
Measured: 4 hours
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.
Measured: 24 hours
Cortical Excitability in DLPFC Using TMS-EEG
Measured: 7 days
Secondary outcomes (4)
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
Measured: Baseline
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
Measured: 4 hours
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
Measured: 24 hours
Safety as Indicated by Number of Adverse Events
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2016 (estimated)
- Study start14 Oct 2016
- Primary completion16 Aug 2017
- Study completion16 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sudhakar Selvaraj, The University of Texas Health Science Center, Houston
- Investigators
- Sudhakar Selvaraj, MBBS, DPhil, Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02935595
- Sponsor's protocol ID
- HSC-MS-16-0705
- Acronym
- ketamine
- Status last verified
- Jan 2022
- First submitted
- 12 Oct 2016
- Last updated
- 13 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Systematic Investigation of Neurophysiological Correlates of Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
- ClinicalTrials.gov ID
- NCT02935595
- Acronym / sponsor ID
- ketamine / HSC-MS-16-0705
- Conditions
- Treatment Resistant Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- 14 Oct 2016 (actual)
- Primary completion
- 16 Aug 2017 (actual)
- Study completion
- 16 Aug 2017 (actual)
- First posted
- 17 Oct 2016 (estimated)
- Results
- Posted 31 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineSlow infusions of ketamine will take place over a time period of 40 minutes. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (11 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Ketamine HydrochlorideKetamine Hydrochloride Injection | Drug | Ketamine |
Primary outcome
Cortical Excitability in the Dorsolateral Prefrontal Cortex (DLPFC) as Assessed by Transcranial Magnetic Stimulation-evoked Activity Detected by Electroencephalography (TMS-EEG)
Time frame: Baseline
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
Time frame: 4 hours
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
Time frame: 24 hours
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
Time frame: 7 days
4 secondary outcomes
Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Baseline
Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 4 hours
Severity of Depressive Symptoms as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 24 hours
Safety as Indicated by Number of Adverse Events
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Treatment Resistant Depression
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sudhakar Selvaraj, MBBS, DPhil principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine in people with Treatment Resistant Depression, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortical Excitability in the Dorsolateral Prefrontal Cortex (DLPFC) as Assessed by Transcranial Magnetic Stimulation-evoked Activity Detected by Electroencephalography (TMS-EEG) (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2022.