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

November 1, 2023 updated by: Adam Carrico, PhD, Florida International University
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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Contact:
        • Principal Investigator:
          • Adam W Carrico, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 17 or greater
  5. If prescribed antidepressants, on a stable regimen and dose for at least 2 months
  6. C-Reactive Protein (CRP) of 1 mg/L or greater
  7. Suppressed HIV viral load (< 200 copies/mL)
  8. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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 12 individual sessions focused on depression and one session of ART Adherence counseling during the four months following randomization.
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.
This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.
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 12 individually delivered CBT-AD sessions focused on depression.
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.
This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Adam W Carrico, PhD, University of Miami

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2022

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

October 31, 2025

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)

November 2, 2023

Last Update Submitted That Met QC Criteria

November 1, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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