Ignite Creation Date:
2024-05-06 @ 5:28 PM
Last Modification Date:
2024-10-26 @ 2:30 PM
Study NCT ID:
NCT05329441
Status:
RECRUITING
Last Update Posted:
2024-05-20
First Post:
2022-04-08
Brief Title:
Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression
Sponsor:
University of California Los Angeles
Organization:
University of California Los Angeles
Study Overview
Official Title:
Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression Toward Predictors of Treatment Response and Clinical Course
Status:
RECRUITING
Status Verified Date:
2024-05
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:
TIGER
Brief Summary:
Despite the prevalence and significant public health concern over depression among adolescents up to 40 of depressed adolescents do not respond to first-line antidepressants herein termed treatment non-response TNR The goal of this project is to recruit and assess 160 treatment-seeking depressed adolescents and test whether acute stress impacts peripheral levels of inflammation and downstream levels of glutamate in corticolimbic regions previously associated with depression whether these stress-related biomarkers predict TNR to a 12-week trial of either fluoxetine or escitalopram and whether these stress-related biomarkers predict 18-month clinical course
Detailed Description:
Despite the prevalence and public health significance of depression up to 40 of depressed adolescents do not respond to first-line antidepressants ie serotonin selective reuptake inhibitors SSRIs Adolescents with treatment non-response TNR are at high risk for physical and mental health difficulties associated with ineffectively treated depression including cardiovascular disease and suicide Thus identifying the neurobiological mechanisms that underlie TNR in adolescents is a critical step toward optimizing treatment plans for those who do not respond to first-line treatments In this context sustained threat to social stressors as measured by elevated inflammatory profiles to stressful stimuli has been shown to drive the onset and maintenance of depression among adolescents and is associated with TNR The mechanisms by which elevated inflammation impact the brain in depressed adolescents however are unclear To address these gaps in our knowledge the investigators will test the central hypothesis that excessive glutamate Glu in depression-related corticolimbic circuits-including the anterior cingulate cortex ventromedial prefrontal cortex amygdala and hippocampus-is a critical mediator between peripheral inflammation and TNR in depressed adolescents Specifically the investigators will conduct a prospective 18-month study of 160 unmedicated treatment-seeking depressed adolescents using state-of-the-art multimodal neuroimaging data at 7 Tesla At Time 1 prior to SSRI treatment and Time 2 after an open-label 12-week SSRI trial the investigators will assess peripheral measures of pro-inflammatory cytokines and glutamate in corticolimbic circuits before and after a well-validated adolescent-version of the Trier Social Stress Test TSST At Time 1 the investigators will test if TSST induces increases in inflammation and glutamate in corticolimbic circuits in unmedicated adolescents with depression At Time 2 the investigators will use machine learning methods to identify multi-level predictors of TNR based on behavioral inflammatory and neural indicators of sustained threat to social stress the investigators will also test whether glutamate in corticolimbic circuits mediates the association between baseline levels of inflammation and TNR Finally as an exploratory aim the investigators will continue to clinically assess depression symptoms and collect information on social stressors eg context severity duration every 3 months for 15 months following Time 2 ie from Time 3 to Time 7 which will enable the use of functional clustering analyses to identify subgroups of adolescents on the basis of depression trajectories eg persistent depression gradual remission etc and identify predictors of these subgroups and other related clinical outcomes eg remission status while accounting for the effects of TNR status and any changes in treatment and other related factors including stressful life events Results from this work will motivate future studies testing alternative therapeutics for depressed adolescents at risk for treatment resistant depression
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None