Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT) (TRIDENT)

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.

Study Overview

• Status: Recruiting
• Conditions: Depression; Inflammation; HIV-1-infection
• Intervention / Treatment: Behavioral: Antiretroviral Therapy (ART) Adherence Counseling; Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD)

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adam W Carrico, PhD; Phone Number: (305) 348-7887; Email: acarrico@fiu.edu

Study Locations

• United States
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Recruiting
      • University of Miami Neuroimaging Facility
      • Contact: Roger McIntosh, PhD; Phone Number: 305-243-2047; Email: r.mcintosh@miami.edu
    • Miami, Florida, United States, 33137
      • Recruiting
      • Care Resource - Midtown Miami
      • Contact: Adam W Carrico, PhD; Phone Number: (305) 348-7887; Email: acarrico@fiu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. 5. Otherwise eligible but does not complete the run-in period that includes the baseline assessment, biospecimen collection, the fMRI visit, and a separately scheduled randomization visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD); Participants randomized to receive CBT-AD immediately will complete up to 15 individual sessions (12 session with 3 booster sessions) focused on depression and one session of ART Adherence counseling during the four months following randomization.	Behavioral: Antiretroviral Therapy (ART) Adherence Counseling; This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.; Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD); CBT-AD is a behavioral intervention administered either in person or via Zoom. Each session lasts approximately 50 minutes. Participants will receive up to 12 individually delivered sessions over 4 months. Participants receive up to three individually delivered booster sessions through 6 months.
Experimental: Wait-List Control (WLC); Participants randomized to the WLC condition will receive one session of ART adherence counseling immediately following randomization. After six months, WLC participants will have the opportunity to receive 15 individually delivered CBT-AD sessions (12 sessions and 3 booster sessions) focused on depression.	Behavioral: Antiretroviral Therapy (ART) Adherence Counseling; This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.; Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD); CBT-AD is a behavioral intervention administered either in person or via Zoom. Each session lasts approximately 50 minutes. Participants will receive up to 12 individually delivered sessions over 4 months. Participants receive up to three individually delivered booster sessions through 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in resting state activation of the negative valence system	Measured by functional Magnetic Resonance Imaging (fMRI)	6 Months
Change in connectivity of the negative valence system	Measured by functional Magnetic Resonance Imaging (fMRI)	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depressive Symptoms	The Hamilton Rating Scale for Depression is an interviewer-administered measure that has a total score ranging from 0-52 with the higher score indicating greater depressive symptoms	6 Months
Conserved transcriptional response to adversity (CTRA) leukocyte signaling pathway	Measured using Ribonucleic Acid (RNA) sequencing from peripheral blood mononuclear cells	4 Months
Soluble Markers of Microbial Translocation	Enzyme-linked immunosorbent assay (ELISA) methods will be employed to measure lipopolysaccharide binding protein (LBP) levels in plasma samples. Log10 will be the unit of measure.	4 Months
Soluble Markers of Immune Activation and Inflammation	Enzyme-linked immunosorbent assay (ELISA) methods will be employed to measure levels of monocyte activation markers (i.e., soluble CD14, soluble CD163) and pro-inflammatory cytokines (e.g., interleukin, high sensitivity c-reactive protein) in plasma samples. Log10 will be the unit of measure.	4 Months
Soluble Markers of Dysregulated Neurotransmitter Synthesis	High performance liquid chromatography method with fluorescence will measure mean levels of the kynurenine/tryptophan and phenylalanine/tyrosine ratios in plasma samples. Log10 will be the unit of measure.	4 Months
Neurocognitive Functioning	Changes in mean levels of measures indexing executive functioning, attention, and affect regulation assessed in a comprehensive, interviewer-administered neuropsychological assessment battery. Units will be expressed as standardized scores (i.e., T scores).	6 Months
Alterations in gut microbiota	Measured via 16s sequencing of the gut microbiome using rectal swabs and fecal samples	4 months

Collaborators and Investigators

• Sponsor: Florida International University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Adam W Carrico, PhD, Florida International University

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 29, 2021

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Microbiome; HIV; Brain; Gut; CBT-AD
• Additional Relevant MeSH Terms: Pathologic Processes; Behavioral Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Depression; Inflammation; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy
• Other Study ID Numbers: 20210773; R01MH128868 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No