Stress and Pain in People Living With HIV (HIV Stress)

Stress-immune Mechanisms for People Living With HIV, CUD and Depression

This is a basic human experimental study utilizing 4 groups of individuals with and without HIV and complex morbidities of cannabis use disorder and major depression who will participate in 2 sessions of the Yale Pain Stress Task (YPST) and follow-up phase to assess drug use and mood symptoms.

Study Overview

• Status: Recruiting
• Conditions: Depression; Pain; Stress; HIV; Cannabis Use Disorder
• Intervention / Treatment: Other: Yale Pain Stress Task (YPST)

Detailed Description

This study aims to address research gaps using a powerful and novel cross-diagnostic approach with multiple complementary approaches to examine the overarching hypothesis that PLWH+CM exhibit impaired stress-related HPA and HPA-immune function due to alterations in epigenetic mechanisms, and these stress-related HPA-immune and related epigenetic aberrations predict distress, craving and substance use symptoms underlying PLWH complex morbidities. This hypothesis will be tested using a combined human experimental stress challenge approach with prospective longitudinal assessment of daily distress, and substance use symptoms as well as assessment of chronic stress (C-stress), social determinants of health (SDoH), and resilience in experimental cohorts of PLWH with and without CM and those without HIV with and without CM.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rachel Hart, MA; Phone Number: 203-737-4791; Email: Rachel.hart@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • The Yale Stress Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• good health as verified by screening examination
• Able to read English and complete study evaluations and provide informed written and verbal consent. Additional criteria PLWH
• HIV-1 lab test positive
• undetectable viral load
• good ART adherence

Additional criteria by group:

PLWH +CM:

• CB positive urine toxicology
• meet DSM-5 criteria for CUD and MDD as assessed using SCID-I. HC
• HIV-1 test negative
• urine toxicology negative
• no major medical and psychiatric diagnoses based on DSM-V.

PLWH Only:

• HIV-1 test positive
• urine toxicology negative
• no major medical and psychiatric diagnoses based on DSM-V.

CM Only:

• HIV-1 test negative
• urine toxicology positive
• meet DSM-5 criteria for CUD and MDD as assessed using SCID-I

Exclusion Criteria:

• meet primary, current moderate and severe criteria for other SUD including cocaine, alcohol, opiates, sedatives, nicotine
• current use or past history of cocaine or opioid use disorder
• history of any psychotic disorder
• current diagnoses of bipolar disorder and PTSD
• psychotic or otherwise severely psychiatrically disabled (i.e., suicidal, homicidal, current mania)
• significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology that would interfere with study participation
• medications with known central effects on HPA axis and cytokines/immune function
• women who are pregnant, nursing or those using hormonal birth control that affect HPA axis cortisol responses.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIV-positive (PLWH+); Participants that are HIV-positive only will undergo 2 Within Subjects factors of Condition, Stress and No Stress (order of condition randomly assigned and counterbalanced)	Other: Yale Pain Stress Task (YPST); Individuals in the experimental cohort will be scheduled for 2 experimental sessions 1-3 days apart. The YPST stress experiment includes a stress and no-stress session (order randomly assigned, counter-balanced across subjects), and involves multiple (up to 3) unpredictable number of consecutive 3-minute trials of ice-bath (stress) or warm-bath (no stress) forearm immersion (stress) with subjective, physiologic endocrine and immune assessments repeated at specified time points.
Experimental: HIV-positive and complex morbidity (PLWH/CM+); Participants that are HIV-positive with complex morbidities will undergo 2 Within Subjects factors of Condition, Stress and No Stress (order of condition randomly assigned and counterbalanced)	Other: Yale Pain Stress Task (YPST); Individuals in the experimental cohort will be scheduled for 2 experimental sessions 1-3 days apart. The YPST stress experiment includes a stress and no-stress session (order randomly assigned, counter-balanced across subjects), and involves multiple (up to 3) unpredictable number of consecutive 3-minute trials of ice-bath (stress) or warm-bath (no stress) forearm immersion (stress) with subjective, physiologic endocrine and immune assessments repeated at specified time points.
Experimental: Healthy control (HC); Participants that are not HIV-positive and no complex morbidities will undergo 2 Within Subjects factors of Condition, Stress and No Stress (order of condition randomly assigned and counterbalanced)	Other: Yale Pain Stress Task (YPST); Individuals in the experimental cohort will be scheduled for 2 experimental sessions 1-3 days apart. The YPST stress experiment includes a stress and no-stress session (order randomly assigned, counter-balanced across subjects), and involves multiple (up to 3) unpredictable number of consecutive 3-minute trials of ice-bath (stress) or warm-bath (no stress) forearm immersion (stress) with subjective, physiologic endocrine and immune assessments repeated at specified time points.
Experimental: Control and complex morbidity (HC+CM); Participants that are not HIV-positive and have complex morbidities will undergo 2 Within Subjects factors of Condition, Stress and No Stress (order of condition randomly assigned and counterbalanced)	Other: Yale Pain Stress Task (YPST); Individuals in the experimental cohort will be scheduled for 2 experimental sessions 1-3 days apart. The YPST stress experiment includes a stress and no-stress session (order randomly assigned, counter-balanced across subjects), and involves multiple (up to 3) unpredictable number of consecutive 3-minute trials of ice-bath (stress) or warm-bath (no stress) forearm immersion (stress) with subjective, physiologic endocrine and immune assessments repeated at specified time points.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cortisol levels	Mean change in cortisol levels (pg/ml) assessed using repeated blood sampling over 2 hour period on 2 separate days to extract plasma for cortisol measurement using standard RIA assay procedures.	day 1 and day 3
Change in adrenocorticotropic hormone (ACTH) levels	Mean change in pain stress assessed using repeated blood sampling over 2 hour period on 2 separate days to extract plasma for ACTH measurement using standard RIA assay procedures.	day 1 and day 3
Change in pain stress	Mean change in pain stress assessed using repeated sampling over 2 hour period on 2 separate days using 10-point visual analog scales (VAS) where 0 is not at all and 10 is the most pain being experienced.	day 1 and day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean behavioral pain tolerance	Time in seconds that hand remains immersed in ice cold and warm water over 3 trials of 3 minutes each as a measure of behavioral pain tolerance	day 1 or day 3
Mean Heart Rate	Heart rate (bpm) assessed using repeated sampling over 2 hour period on 2 separate days using standard heart rate monitor.	day 1 and day 3
Mean Blood pressure (systolic and diastolic)	Blood pressure (mmHg), systolic and diastolic,assessed using repeated sampling over 2 hour period on 2 separate days using standard blood pressure monitor.	day 1 and day 3

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Rajita Sinha, Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2025
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): January 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Behavioral Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Pain; Depression
• Other Study ID Numbers: 2000038503; 1R01DA061995-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual de-identified data will be uploaded into National Institute of Mental Health Data Archive (NDA) data repository.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No