Depression, HIV-1-infection, Inflammation
Conditions
Keywords
Depression, Microbiome, HIV, CBT-AD, Gut, Brain
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.
Interventions
BEHAVIORALCognitive-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.
BEHAVIORALAntiretroviral Therapy (ART) Adherence Counseling
This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.
Sponsors
Florida International University
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in resting state activation of the negative valence system | 6 Months | Measured by functional Magnetic Resonance Imaging (fMRI) |
| Change in connectivity of the negative valence system | 6 Months | Measured by functional Magnetic Resonance Imaging (fMRI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Alterations in gut microbiota | 4 months | Measured via 16s sequencing of the gut microbiome using rectal swabs and fecal samples |
| 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 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. |
| 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. |
| 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). |
Countries
United States
Contacts
CONTACTAdam W Carrico, PhD
PRINCIPAL_INVESTIGATORAdam W Carrico, PhD
Florida International University
Outcome results
None listed