Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)

Depression Clinical Trial

— TRIDENT  

Official title:

Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05136703
• Other study ID #: 20210773
• Secondary ID: R01MH128868
• Status: Recruiting
• Phase: N/A
• Start date: August 30, 2022
• Est. completion date: October 31, 2025

Study information

• Verified date: November 2023
• Source: Florida International University
• Contact: Adam W Carrico, PhD
• Phone: (305) 348-7887
• Email: acarrico[@]fiu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• HIV-1-infection
• Inflammation

Intervention

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.
• Antiretroviral Therapy (ART) Adherence Counseling
This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.

Locations

Country	Name	City	State
United States	University of Miami	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Florida International University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in resting state activation of the negative valence system	Measured by functional Magnetic Resonance Imaging (fMRI)	6 Months
Primary	Change in connectivity of the negative valence system	Measured by functional Magnetic Resonance Imaging (fMRI)	6 Months
Secondary	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
Secondary	Alterations in gut microbiota	Measured via 16s sequencing of the gut microbiome using rectal swabs and fecal samples	4 months
Secondary	Conserved transcriptional response to adversity (CTRA) leukocyte signaling pathway	Measured using Ribonucleic Acid (RNA) sequencing from peripheral blood mononuclear cells	4 Months
Secondary	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
Secondary	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
Secondary	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
Secondary	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