Clinical trial NCT05136703: Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)
Official title: Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depression
HIV-1-infection
Inflammation
Keywords: Depression
Microbiome
HIV
CBT-AD
Gut
Brain
Lead sponsor: Florida International University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2021-11-29
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this randomized controlled trial is to understand how a cognitive-behavioral treatment (a form of psychological treatment) for depression changes the gut microbiome (micro-organisms that regulate the health of the gut), immune system, and the brain functioning in people living with HIV.

Detailed description: The overarching goal of this randomized controlled trial (RCT) is to identify the causal pathways that drive depressive symptoms among people with HIV (PWH). The scientific premise is that evidence-based depression treatment is an innovative, experimental probe to determine the neural substrates of depression and mechanistic relevance of microbiome-gut-brain (MGB) axis changes during and after Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) on brain and behavioral function.

The proposed causal pathway is that reductions in depressive symptoms following the delivery of CBT-AD treatment will trigger a cascade of alterations in the MGB axis. Specifically, CBT-AD related decreases in depressive symptoms will induce alterations in gut dysbiosis, decrease microbial translocation, and improve soluble neuroactive markers of peripheral immune dysregulation. Our efforts to elucidate the immunologic mechanisms whereby CBT-AD could improve neurobehavioral outcomes will also focus on an established leukocyte signaling pathway, the Conserved Transcriptional Response to Adversity (CTRA), which has been shown to be responsive to behavioral interventions and psychosocial factors outside of HIV.

Eligibility criteria: Inclusion Criteria:

1. Age 18 or older
2. Speaks and reads English
3. Verified HIV+ status with antiretroviral medications bearing his/her name
4. Current diagnosis on Major Depressive Disorder (MDD) using a structured clinical interview (DIAMOND) or Hamilton Rating Scale for Depression scores of 7 or greater
5. If prescribed antidepressants, on a stable regimen and dose for at least 2 months
6. Suppressed HIV viral load (\< 200 copies/mL)
7. Able to complete Functional Magnetic Resonance Imaging (fMRI) scans (i.e., no claustrophobia, no metal implants, no pacemaker, and BMI \< 40)

Exclusion Criteria:

1. Unable to provide informed consent
2. Active, untreated major mental illness
3. Pregnancy at baseline
4. Received CBT for depression in the past 2 years
5. Otherwise eligible but does not complete baseline biospecimen collection and fMRI visit

Primary outcomes:
measure: Change in resting state activation of the negative valence system
timeFrame: 6 Months
measure: Change in connectivity of the negative valence system
timeFrame: 6 Months
Secondary outcomes:
measure: Depressive Symptoms
timeFrame: 6 Months
measure: Alterations in gut microbiota
timeFrame: 4 months
measure: Conserved transcriptional response to adversity (CTRA) leukocyte signaling pathway
timeFrame: 4 Months
measure: Soluble Markers of Microbial Translocation
timeFrame: 4 Months
measure: Soluble Markers of Immune Activation and Inflammation
timeFrame: 4 Months
measure: Soluble Markers of Dysregulated Neurotransmitter Synthesis
timeFrame: 4 Months
measure: Neurocognitive Functioning
timeFrame: 6 Months
Other outcomes:
Locations:
city: Coral Gables
country: United States
facility: University of Miami Neuroimaging Facility
state: Florida
city: Miami
country: United States
facility: Care Resource - Midtown Miami
state: Florida
Study officials:
affiliation: Florida International University
name: Adam W Carrico, PhD
role: PRINCIPAL_INVESTIGATOR
References: