Project neuroARTEMIS

Not Applicable

Recruiting

• Conditions: Stimulant Use; Human Immunodeficiency Virus (HIV); Depression

• Registration Number: NCT06814275
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

The purpose of this research is to understand how chronic stress affects the way our brain and immune systems function, and in turn how this affects the way people feel, think, and behave. By learning more about how these processes work, the hope is to be able to develop better treatments to help with problems like depression and substance use. This study is intended for individuals that are HIV positive, currently taking prescription antiretroviral medications, and use stimulants. Through this intervention, the aim is to determine if this positive affect intervention can lead to reductions in stimulant use and depressed mood.

Detailed Description

Participants who meet initial eligibility criteria will complete a baseline assessment that includes psychosocial and behavioral measures, biospecimen collection, and an MRI brain scan. Participants will then be randomized to either: 1) ARTEMIS; or 2) a waitlist control (WLC) condition. ARTEMIS participants will receive 5 sessions delivered individually over Zoom across 3 months. All participants (including WLC) will receive contingency management (CM) for antiretroviral therapy (ART) adherence to support sustained viral suppression over the active phase of the trial. During the intent-to-treat period, assessments at 3- and 6-month follow-ups will characterize changes in neural activity (assessed via fMRI) and conserved transcriptional response to adversity (CTRA) leukocyte signaling (assessed via RNA sequencing) as plausible mediators of behavioral outcomes following ARTEMIS. WLC participants will be offered the ARTEMIS intervention after a 6-month delay.

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2025-02-03
• Study First Submitted QC: 2025-02-03
• Study First Posted: 2025-02-07
• Study Start: 2025-04-29
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-01
• Primary Completion: 2028-05-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 189

Inclusion Criteria

• 18-59 years old
• Weekly use of stimulants reported in the past month or a score of 4 or more on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)
• Confirmed HIV diagnosis
• Current receipt of daily oral antiretroviral therapy (ART) medication
• English fluency/literacy

Exclusion Criteria

• Acute brain infection (e.g., neurosyphilis, toxoplasmosis)
• Acutely symptomatic bipolar I or psychotic disorder
• Prescription for immunomodulatory medications or other immunotherapy
• Any MRI contraindications
• If applicable, on antidepressant medication regimen for at least 2 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Neural Functional Connectivity	Month 3	Functional connectivity (FC) will be derived from the the resting-state functional MRI data. Using a theory-driven, seed-based approach, the 4D time series \[average blood oxygenation level dependent (BOLD) signal across voxels\] will be extracted from a priori seeds in the reward network (i.e., nucleus accumbens, subgenual anterior cingulate cortex, medial orbitofrontal cortex). Normalized Z-scores will be calculated for FC between regions of interest. These analyses will control for baseline FC.
Neural Activation	Month 3	The Monetary Incentive Delay Task will be used to probe neural activation to reward processing, using an event-level design. Blood oxygenation level dependent (BOLD) activation will be modeled as a canonical hemodynamic response function specified at stimulus onset. Event epochs that are time locked to the onset of each trial will be extracted from the overall time series. Random-effects general linear model will be used to calculate statistical parametric maps reflecting the probability that a voxel is activated as a function of the experimental task. The primary analysis will focus on nucleus accumbens and ventromedial prefrontal cortex activity as regions of interest (ROI). Mean beta values will be averaged across all voxels in each ROI. These analyses will control for baseline activation levels.

Secondary Outcome Measures

Name	Time	Method
Change in Frequency of Stimulant Use	3 and 6 month follow-ups	Utilizing a Timeline Follow-back, days of stimulant use in past 30 will be assessed. Stimulants will include methamphetamine, other amphetamines, cocaine, and other stimulants. Change in use from baseline will be examined.
Depression Scores	3 and 6 month follow-ups	Depression symptom severity, measured via (CES) Center for Epidemiologic Studies Depression Scale. This assessment is a 20 item assessment with each item being assigned a value of 0-3. Higher scores are indicative of depression. The total score is calculated by calculating the sum of 20 items. Scores range from 0-60, with higher scores meaning greater depressive symptoms. We will examine change from baseline.
CTRA Leukocyte Signaling	Baseline, Month 3, Month 6	RNA sequencing (RNAseq) of peripheral blood mononuclear cells (PBMCs) will be conducted for analysis of differential gene expression, detection of low expressed genes, allele specific expression analysis, and splice variants. Gene expression values will be log2-transformed and pre-specified sets of inflammatory and Type I interferon genes will be combined into a single-number CTRA indicator (53-gene contrast score).
Change in Peripheral Inflammation	3 and 6 month follow-ups	Plasma samples will undergo multiplexed analysis for key inflammatory mediators: CRP, TNF-a, IFN-g, IL-1b, IL-6, CXCL10, and CCL2. Single-enzyme-linked immunoabsorbent assays (ELISAs) will be performed for sCD14 and sCD163. We will examine changes in concentration from baseline.

Trial Locations

Locations (1)

Wake Forest University School of Medicine; 🇺🇸 Winston-Salem, North Carolina, United States