Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)

Not Applicable

Recruiting

• Conditions: HIV-1-infection; Depression; Inflammation
• Interventions: Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD); Behavioral: Antiretroviral Therapy (ART) Adherence Counseling

• Registration Number: NCT05136703
• Lead Sponsor: Florida International University

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.

Study Timeline

• Study First Submitted: 2021-11-15
• Study First Submitted QC: 2021-11-15
• Study First Posted: 2021-11-29
• Study Start: 2022-08-30
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-02
• Last Update Posted: 2025-02-05
• Primary Completion: 2026-09-30
• Study Completion: 2027-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Wait-List Control (WLC)	Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD)	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 12 individually delivered CBT-AD sessions focused on depression.
Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD)	Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD)	Participants randomized to receive CBT-AD immediately will complete up to 12 individual sessions focused on depression and one session of ART Adherence counseling during the four months following randomization.
Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD)	Antiretroviral Therapy (ART) Adherence Counseling	Participants randomized to receive CBT-AD immediately will complete up to 12 individual sessions focused on depression and one session of ART Adherence counseling during the four months following randomization.
Wait-List Control (WLC)	Antiretroviral Therapy (ART) Adherence Counseling	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 12 individually delivered CBT-AD sessions focused on depression.

Primary Outcome Measures

Name	Time	Method
Change in connectivity of the negative valence system	6 Months	Measured by functional Magnetic Resonance Imaging (fMRI)
Change in resting state activation of the negative valence system	6 Months	Measured by functional Magnetic Resonance Imaging (fMRI)

Secondary Outcome Measures

Name	Time	Method
Depressive Symptoms	6 Months	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
Soluble Markers of Microbial Translocation	4 Months	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.
Alterations in gut microbiota	4 months	Measured via 16s sequencing of the gut microbiome using rectal swabs and fecal samples
Soluble Markers of Dysregulated Neurotransmitter Synthesis	4 Months	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.
Neurocognitive Functioning	6 Months	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).
Conserved transcriptional response to adversity (CTRA) leukocyte signaling pathway	4 Months	Measured using Ribonucleic Acid (RNA) sequencing from peripheral blood mononuclear cells
Soluble Markers of Immune Activation and Inflammation	4 Months	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.

Trial Locations

Locations (2)

University of Miami Neuroimaging Facility; 🇺🇸 Coral Gables, Florida, United States

Care Resource - Midtown Miami; 🇺🇸 Miami, Florida, United States