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Biological Response to Brief Psychological Challenge

Primary Purpose

Acute Inflammatory Response to Psychological Stress

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Socio-evaluative speech task

Control, Quiet Rest

About this trial

This is an interventional basic science trial for Acute Inflammatory Response to Psychological Stress

Eligibility Criteria

20 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Generally healthy
Non-smokers/illicit drug users
Blood pressure below 140/90
Weight > 110 lbs
BMI < 30
Fluent in English
Women -- regular menstrual cycles over the past 12 months (defined as 21- 35 days in length)
Able and willing to give informed consent
Willing to abstain from alcohol and vigorous exercise for 24 hours, from food and drinks (other than water) for 3 hours and from non-prescription medications (other than oral contraception) for 2 days before testing.
Willing to attend two laboratory stress testing sessions, give blood though an intravenous catheter, undergo medical evaluation and complete psychosocial questionnaires.

Exclusion Criteria:

Reported history of chronic systemic immune, metabolic or mitochondrial diseases, or chronic diseases that influence the central nervous, autonomic nervous or neuroendocrine systems, e.g., autoimmune disease, chronic infections, cardiovascular disease, diabetes, chronic kidney or liver disease, cancer treatment.
Reported psychiatric history of schizophrenia or other psychotic illness, or mood disorder.
Resting blood pressure > 140/90 mmHg at baseline testing.
Weight < 110 lbs
BMI equal to or greater than 30
Report currently taking glucocorticoid, anti-inflammatory, anti-retroviral, immunosuppressant, insulin, antiarrhythmic, antihypertensive, oral hypoglycemic, antidepressant, benzodiazepine or prescription weight loss medications or other medications known to influence the immune, autonomic or neuroendocrine systems.
For women - Post-menopausal or irregular menstrual cycles over the past 12 months. Report current pregnancy or lactation.
Current smokers (defined as having smoked a cigarette in the previous 3 months).
Current illicit drug use (defined as reported use of illicit drugs such as marijuana, cocaine or heroin in the previous 3 months).
Not fluent in English (have used English in everyday speaking and reading for at least 10 years)
Unable or unwilling to give informed consent
Unwilling to abstain from alcohol and vigorous exercise for 24 hours, from food and drinks (other than water) for 3 hours and from non-prescription medications (other than oral contraception) for 2 days prior to testing.

Sites / Locations

University of Pittsburgh

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Socio-evaluative Speech Stress, then Control

Control, then Socio-Evaluative Speech Stress

Arm Description

Participants will attend two laboratory sessions. At the first session, participants will complete a socio-evaluative speech task, which is a widely used, highly effective way to investigate stress responses in a laboratory setting. Participants will prepare and deliver a brief, 3-minute speech defending themselves against an alleged transgression (e.g., running a stop sign). The speech will be delivered in front of a video camera, a mirror and an audience (the interviewer and another staff member). Participants will be told that their non-verbal behaviors are being evaluated. At the second session, participants will rest quietly for the same period as the speech task, in the absence of the stressor.

Participants will attend two laboratory sessions. At the first session, participants will rest quietly for 5 minutes. At the second session, participants will complete a socio-evaluative speech task, which is a widely used, highly effective way to investigate stress responses in a laboratory setting. Participants will prepare and deliver a brief, 3-minute speech defending themselves against an alleged transgression (e.g., running a stop sign). The speech will be delivered in front of a video camera, a mirror and an audience (the interviewer and another staff member). Participants will be told that their non-verbal behaviors are being evaluated.

Outcomes

Primary Outcome Measures

Change in cell-free mitochondrial DNA

Plasma and serum levels of mitochondrial DNA will be assessed as change across all measures using linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects

Change in interleukin-6

Plasma levels of interleukin-6 will be assessed as change across all measures using linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects

Change in tumor necrosis factor-alpha

Plasma levels of tumor necrosis factor-alpha will be assessed as change across all measures using linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects

Secondary Outcome Measures

Change in heart rate

Continuous measurement of heart rate will be assessed using a cuff placed on a finger. Linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects will be employed to assess change in heart rate across time.

Change in systolic and diastolic blood pressure

Continuous measurement of blood pressure will be assessed using a cuff placed on a finger. Linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects will be employed to assess change in blood pressure across time.

Change in cortisol

Circulating levels of cortisol assessed by ELISA will be assessed as change across all measures using linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects

Change in epinephrine

Levels of epinephrine in plasma from blood samples will be assessed as change across all measures using linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects

Change in norepinephrine

Levels of norepinephrine in plasma from blood samples will be assessed as change across all measures using linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects

Change in heart rate variability

Interbeat intervals of heart rate assessed by 3-lead EKG will be assessed as change across all measures using linear mixed models (with subject and day (nested within subject) as random effects, and condition (stress/control) as fixed effects

Change in Fatigue

Momentary assessment of fatigue, measured as score on the fatigue subscale on the Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 20, with higher scores reflecting more fatigue.

Change in anger

Momentary assessment of anger, measured as score on the anger subscale on the Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more anger.

Change in anxious mood

Momentary assessment of anxious mood, measured as score on the anxiety subscale on the Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more anxious mood.

Change in depressed mood

Momentary assessment of depressed mood, measured as score on the depression subscale on the Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more depressed mood.

Change in vigor

Momentary assessment of vigor, measured as score on the vigor subscale on the Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more vigor.

Change in wellbeing

Momentary assessment of wellbeing, measured as score on the wellbeing subscale on the Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more wellbeing.

Change in calm mood

Momentary assessment of calm mood, measured as score on the calm subscale on the Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more calm mood.

Full Information

NCT ID

NCT04078035

First Posted

August 28, 2019

Last Updated

December 14, 2022

Sponsor

University of Pittsburgh

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT04078035

Brief Title

Biological Response to Brief Psychological Challenge

Official Title

Transduction of Psychological Stress Into Systematic Inflammation by Mitochondrial DNA Signaling

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

July 23, 2020 (Actual)

Primary Completion Date

January 31, 2022 (Actual)

Study Completion Date

January 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Pittsburgh

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The investigators plan to conduct a crossover experimental trial examining physiological responses to a socio-evaluative speech task under laboratory conditions. Participants will attend two laboratory sessions. At one session participants will take part in a brief laboratory stress task and at the other participants will rest for the same period. Measures of cardiovascular response will be assessed at both sessions. In addition, blood will be drawn at multiple time points across a 125 minute period to assess changes in circulating levels of cortisol, catecholamines, markers of inflammation and cell free mitochondrial DNA in response to the task. The investigators expect that the stress task will induce a specific increase in ccf-mtDNA, which will statistically mediate subsequent peak circulating Interleukin-6 and Tumor Necrosis Factor-α levels. In secondary analyses, the investigators will examine whether stress-induced increases in circulating cortisol, epinephrine, and norepinephrine levels correlate with increases in ccf-mtDNA. These studies will establish the kinetics and magnitude of psychological stress-induced ccf-mtDNA release, the association with early stress mediators, and whether ccf-mtDNA mediates the inflammatory response to acute stress in humans.

Detailed Description

The proposed study will examine physiologic responses to acute psychological challenge in the laboratory among healthy adults. It is widely accepted that there is an increase in circulating markers of inflammation following a single bout of laboratory stress. This increase in systemic inflammation is believed to contribute to the damaging health effect of psychological stress. However, to date, the biological mechanisms by which psychological stress is transduced into inflammation are unclear. The investigators' preliminary evidence suggests that mitochondrion may play a role, with stress-induced increases in circulating levels of mitochondria- derived signaling molecules that are known to modulate immune cell function and the production of pro-inflammatory cytokines. To test this possibility, the investigators plan to conduct a crossover experimental trial examining physiological responses to an evaluative speech task under laboratory conditions. The investigators have previously used this task to induce physiological arousal. The investigators plan to recruit 60 non-smoking volunteers (50% female, aged 20-50 years) and test these participants on two occasions separated by at least a month. On one occasion the participants will be exposed to the speech task. On the other occasion, the participants will rest quietly for the same period. Conditions will be counterbalanced. At both visits cardiovascular responses (heart rate, blood pressure, and heart rate variability) will be assessed as measures of autonomic activation before, during and after the task period. Participants will also have an intravenous catheter inserted and blood drawn at ten time points over the two hour testing period on each occasion. Blood samples will be sent to laboratories at the University of Pittsburgh and at Columbia University for the assessment of mitochondria-derived signalling molecules, inflammatory markers, and cortisol levels.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Inflammatory Response to Psychological Stress

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

The investigators propose a crossover experimental trial examining physiological responses to a socio-evaluative speech task under laboratory conditions. Participants will be tested on two occasions separated by at least 1 month. On one occasion, participants will be exposed to the speech task. On the other occasion, participants will rest quietly for the same period of time with identical assessment in the absence of the stressor. Conditions will be counterbalanced in randomized starting order across subjects.

Masking

Outcomes Assessor

Masking Description

Samples of plasma and serum will be identified by participant identification number only. Technicians assessing levels of biological measures in these samples will be blind to condition.

Allocation

Randomized

Enrollment

84 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Socio-evaluative Speech Stress, then Control

Arm Type

Experimental

Arm Description

Arm Title

Control, then Socio-Evaluative Speech Stress

Arm Type

Experimental

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Socio-evaluative speech task

Intervention Description

5-minute speech task designed to induce physiological arousal in a laboratory setting.

Intervention Type

Behavioral

Intervention Name(s)

Control, Quiet Rest

Intervention Description

5-minute quiet rest period.

Primary Outcome Measure Information:

Title

Change in cell-free mitochondrial DNA

Description

Time Frame

5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90,120 minutes post-task periods

Title

Change in interleukin-6

Description

Time Frame

5 minutes before to 20, 30, 45, 60, 75, 90, 120 post-task periods

Title

Change in tumor necrosis factor-alpha

Description

Time Frame

5 minutes before to 20, 30, 45, 60, 75, 90, 120 post-task periods

Secondary Outcome Measure Information:

Title

Change in heart rate

Description

Time Frame

Continuously assessed from 10 minutes before to 120 minutes after the task periods.

Title

Change in systolic and diastolic blood pressure

Description

Time Frame

Continuously assessed from 10 minutes before to 120 minutes after the task periods.

Title

Change in cortisol

Description

Time Frame

5 minutes before to 10, 20, 30, 45, 60 minutes post-task periods

Title

Change in epinephrine

Description

Time Frame

5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods

Title

Change in norepinephrine

Description

Time Frame

5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods

Title

Change in heart rate variability

Description

Time Frame

Continuously assessed from 10 minutes before to 120 minutes after the task periods.

Title

Change in Fatigue

Description

Time Frame