Ignite Creation Date:
2024-05-06 @ 2:56 AM
Last Modification Date:
2024-10-26 @ 11:26 AM
Study NCT ID:
NCT02165449
Status:
COMPLETED
Last Update Posted:
2019-08-28
First Post:
2014-06-12
Brief Title:
Biomarkers of Fast Acting Therapies in Major Depression
Sponsor:
University of California Los Angeles
Organization:
University of California Los Angeles
Study Overview
Official Title:
Translational Biomarkers of Fast Acting Therapies in Major Depression
Status:
COMPLETED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
Detailed Description:
Growing evidence implicates the glutamatergic system in the pathogenesis of depression and receptor antagonists may provide a new generation of compounds for MDD treatment In particular the finding that the NMDA antagonist ketamine induces a rapid antidepressant response within hours to days has led to research investigating the neural mechanisms producing rapid antidepressant action and makes ketamine a valuable tool to identify biomarkers of depression response and of risk of relapse The study of biomarkers for understanding the mechanistic actions of ketamine may serve to enhance emerging treatment approaches and provide new breakthroughs for translation of other drug targets
Recently the investigators of this trial have begun to offer off-label ketamine infusion treatment to clinical patients with treatment-resistant depression TRD and have developed a local treatment protocol for systematic clinical assessment infusion monitoring and follow-up which has been well-received and tolerated The overarching goal of this study is to investigate imaging gene expression and immune system biomarkers to help determine the underlying mechanisms and predictors for treatment response and relapse in MDD patients receiving ketamine and to compare these with the same biomarkers obtained from patients receiving ECT The investigators aim to collect data from a sample of 60 patients who will receive serial infusions of ketamine occurring 2-3 times a week until they achieve remission or a total of 4 infusions To study changes during or after ketamine treatment we will use advanced brain scans that will allow us to measure brain structure chemistry and function We will also collect blood samples to measure changes in gene regulation and immune system response at the same time Patients will also be assessed for basic cognitive function and mood Brain and blood sample measurements will occur before ketamine infusion 24 hours after the first infusion after the 4th or last infusion and at a final follow-up session approximately 5 weeks after ketamine treatment We are also including remote mood assessment after treatment to more efficiently track relapse We will therefore be able to see how changes over time in brain measurements and gene regulation or immune response relate to improvements and relapse in depressive symptoms
The investigators will address the following aims
Aim 1 To use a comprehensive multimodal magnetic resonance imaging MRI battery including a single voxel proton magnetic resonance spectroscopy 1HMRS b structural MRI sMRI c arterial spin-labeling ASL d resting state functional MRI rs-fMRI and e diffusion MRI dMRI sensitive to different aspects of brain plasticity to isolate neurobiological markers linked with and predictive of ketamine response and subsequent relapse
Hypothesis 1 Neuroplasticity in cortico-limbic prefrontal and anterior cingulate cortex and hippocampus and striatal networks including changes in glutamate and other brain metabolites in blood perfusion and in structural and functional connectivity will associate with therapeutic response to ketamine
Aim 2 To use peripheral blood to measure inflammatory cytokines and their soluble receptors previously linked with depression or treatment outcome for the examination of relationships with ketamine response and subsequent relapse
Hypothesis 2 Ketamine-induced symptom improvement will associate with altered concentrations of proinflammatory cytokines to indicate modulation of the immune response system
Aim 3 To conduct transcriptome profiling using peripheral blood samples to identify gene expression correlates of ketamine response
Hypothesis 3 Gene expression profiles will signal biological pathways underlying therapeutic response to ketamine
Description of outcome measures
1 Clinical outcome The Hamilton Depression Rating Scale
2 Imaging markers Image analysis will incorporate both standard and custom image analysis software and processing streams to measure changes neurochemistry and structural and functional plasticity and connectivity occurring across time and in association clinical response Specifically outcome measures will include
1 Structural imaging and connectivity measures combined volumetric and shape and diffusion metrics obtained from sMRI and dMRI data
2 Functional connectivity measures Combined functional imaging measures obtained from resting state functional imaging data
3 Neurochemistry Brain metabolites including glutamate choline and NAA
4 Gene expression Gene expression markers obtained from differential expression analyses
Analyses General linear mixed models and regression analyses will be used to determine changes across time and in association with clinical response for imaging markers Weighted Gene Coexpression Network analysis WGCNA and Ingenuity Pathways analysis IPA will be used to identify functions and pathways associated with identified transcripts
Recently the investigators of this trial have begun to offer off-label ketamine infusion treatment to clinical patients with treatment-resistant depression TRD and have developed a local treatment protocol for systematic clinical assessment infusion monitoring and follow-up which has been well-received and tolerated The overarching goal of this study is to investigate imaging gene expression and immune system biomarkers to help determine the underlying mechanisms and predictors for treatment response and relapse in MDD patients receiving ketamine and to compare these with the same biomarkers obtained from patients receiving ECT The investigators aim to collect data from a sample of 60 patients who will receive serial infusions of ketamine occurring 2-3 times a week until they achieve remission or a total of 4 infusions To study changes during or after ketamine treatment we will use advanced brain scans that will allow us to measure brain structure chemistry and function We will also collect blood samples to measure changes in gene regulation and immune system response at the same time Patients will also be assessed for basic cognitive function and mood Brain and blood sample measurements will occur before ketamine infusion 24 hours after the first infusion after the 4th or last infusion and at a final follow-up session approximately 5 weeks after ketamine treatment We are also including remote mood assessment after treatment to more efficiently track relapse We will therefore be able to see how changes over time in brain measurements and gene regulation or immune response relate to improvements and relapse in depressive symptoms
The investigators will address the following aims
Aim 1 To use a comprehensive multimodal magnetic resonance imaging MRI battery including a single voxel proton magnetic resonance spectroscopy 1HMRS b structural MRI sMRI c arterial spin-labeling ASL d resting state functional MRI rs-fMRI and e diffusion MRI dMRI sensitive to different aspects of brain plasticity to isolate neurobiological markers linked with and predictive of ketamine response and subsequent relapse
Hypothesis 1 Neuroplasticity in cortico-limbic prefrontal and anterior cingulate cortex and hippocampus and striatal networks including changes in glutamate and other brain metabolites in blood perfusion and in structural and functional connectivity will associate with therapeutic response to ketamine
Aim 2 To use peripheral blood to measure inflammatory cytokines and their soluble receptors previously linked with depression or treatment outcome for the examination of relationships with ketamine response and subsequent relapse
Hypothesis 2 Ketamine-induced symptom improvement will associate with altered concentrations of proinflammatory cytokines to indicate modulation of the immune response system
Aim 3 To conduct transcriptome profiling using peripheral blood samples to identify gene expression correlates of ketamine response
Hypothesis 3 Gene expression profiles will signal biological pathways underlying therapeutic response to ketamine
Description of outcome measures
1 Clinical outcome The Hamilton Depression Rating Scale
2 Imaging markers Image analysis will incorporate both standard and custom image analysis software and processing streams to measure changes neurochemistry and structural and functional plasticity and connectivity occurring across time and in association clinical response Specifically outcome measures will include
1 Structural imaging and connectivity measures combined volumetric and shape and diffusion metrics obtained from sMRI and dMRI data
2 Functional connectivity measures Combined functional imaging measures obtained from resting state functional imaging data
3 Neurochemistry Brain metabolites including glutamate choline and NAA
4 Gene expression Gene expression markers obtained from differential expression analyses
Analyses General linear mixed models and regression analyses will be used to determine changes across time and in association with clinical response for imaging markers Weighted Gene Coexpression Network analysis WGCNA and Ingenuity Pathways analysis IPA will be used to identify functions and pathways associated with identified transcripts
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U01MH110008 | NIH | None | httpsreporternihgovquickSearchU01MH110008 |
| K24MH102743 | NIH | None | None |