DepressionTRIDENTNCT05136703
Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)
A study testing Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) and Antiretroviral Therapy (ART) Adherence Counseling in people with Depression and HIV-1-infection, run by Florida International University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression, HIV-1-infection, Inflammation
- What is being tested?
- Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) and Antiretroviral Therapy (ART) Adherence Counseling
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Aug 2022to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or older
- Speaks and reads English
- Verified HIV+ status with antiretroviral medications bearing his/her name
- Current diagnosis on Major Depressive Disorder (MDD) using a structured clinical interview (DIAMOND) or Hamilton Rating Scale for Depression scores of 7 or greater
- If prescribed antidepressants, on a stable regimen and dose for at least 2 months
- Suppressed HIV viral load (< 200 copies/mL)
- Able to complete Functional Magnetic Resonance Imaging (fMRI) scans (i.e., no claustrophobia, no metal implants, no pacemaker, and BMI < 40)
Who cannot join
- Unable to provide informed consent
- Active, untreated major mental illness
- Pregnancy at baseline
- Received CBT for depression in the past 2 years
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Miami Neuroimaging Facility
Coral Gables, Florida, 33146
Roger McIntosh, PhD, 305-243-2047, r.mcintosh@miami.edu
- Recruiting
Care Resource - Midtown Miami
Miami, Florida, 33137
Adam W Carrico, PhD, (305) 348-7887, acarrico@fiu.edu
About this study
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.
Read the 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.
- Conditions
- Depression, HIV-1-infection, Inflammation
- Being tested
- Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD), Antiretroviral Therapy (ART) Adherence Counseling
- Keywords
- Depression, Microbiome, HIV, CBT-AD, Gut, Brain
- Medical subject headings
- Depression, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD)Behavioural
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.
Antiretroviral Therapy (ART) Adherence CounselingBehavioural
This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) | Experimental | 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. Receives: Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD); Behavioral: Antiretroviral Therapy (ART) Adherence Counseling |
| Wait-List Control (WLC) | Experimental | 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. Receives: Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD); Behavioral: Antiretroviral Therapy (ART) Adherence Counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in resting state activation of the negative valence system
Measured by functional Magnetic Resonance Imaging (fMRI)
Measured: 6 Months
Change in connectivity of the negative valence system
Measured by functional Magnetic Resonance Imaging (fMRI)
Measured: 6 Months
Secondary outcomes (7)
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
Measured: 6 Months
Alterations in gut microbiota
Measured via 16s sequencing of the gut microbiome using rectal swabs and fecal samples
Measured: 4 months
Conserved transcriptional response to adversity (CTRA) leukocyte signaling pathway
Measured using Ribonucleic Acid (RNA) sequencing from peripheral blood mononuclear cells
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2021
- Study start30 Aug 2022
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Florida International University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Adam Carrico, PhD, Florida International University
- Investigators
- Adam W Carrico, PhD, Principal investigator, Florida International University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05136703
- Sponsor's protocol ID
- 20210773
- Other IDs
- R01MH128868
- Acronym
- TRIDENT
- Status last verified
- Feb 2026
- First submitted
- 15 Nov 2021
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)
- ClinicalTrials.gov ID
- NCT05136703
- Acronym / sponsor ID
- TRIDENT / 20210773
- Conditions
- Depression, HIV-1-infection, Inflammation
- Keywords
- Depression, Microbiome, HIV, CBT-AD, Gut, Brain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Florida International UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 30 Aug 2022 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 29 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) | Experimental | Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD), Behavioral: Antiretroviral Therapy (ART) Adherence CounselingParticipants 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. |
| Wait-List Control (WLC) | Experimental | Behavioral: Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD), Behavioral: Antiretroviral Therapy (ART) Adherence CounselingParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 18 or older
- Speaks and reads English
- Verified HIV+ status with antiretroviral medications bearing his/her name
- Current diagnosis on Major Depressive Disorder (MDD) using a structured clinical interview (DIAMOND) or Hamilton Rating Scale for Depression scores of 7 or greater
- If prescribed antidepressants, on a stable regimen and dose for at least 2 months
Key exclusion criteria (5 listed)
- Unable to provide informed consent
- Active, untreated major mental illness
- Pregnancy at baseline
- Received CBT for depression in the past 2 years
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Behavioural | Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD), Wait-List Control (WLC) |
| Antiretroviral Therapy (ART) Adherence CounselingThis treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach. | Behavioural | Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD), Wait-List Control (WLC) |
Primary outcome
Change in resting state activation of the negative valence system
Time frame: 6 Months
Measured by functional Magnetic Resonance Imaging (fMRI)
Change in connectivity of the negative valence system
Time frame: 6 Months
Measured by functional Magnetic Resonance Imaging (fMRI)
7 secondary outcomes
Depressive Symptoms
Time frame: 6 Months
Alterations in gut microbiota
Time frame: 4 months
Conserved transcriptional response to adversity (CTRA) leukocyte signaling pathway
Time frame: 4 Months
Soluble Markers of Microbial Translocation
Time frame: 4 Months
Soluble Markers of Immune Activation and Inflammation
Time frame: 4 Months
Soluble Markers of Dysregulated Neurotransmitter Synthesis
Time frame: 4 Months
Neurocognitive Functioning
Time frame: 6 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Adam W Carrico, PhD principal investigator
Florida International University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) and Antiretroviral Therapy (ART) Adherence Counseling in people with Depression and HIV-1-infection, run by Florida International University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Adam W Carrico, PhD ((305) 348-7887, acarrico@fiu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in resting state activation of the negative valence system (time frame: 6 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.