University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
NCT Number: NCT04078035
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.
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Notify Me20 year–50 year
All sexes
Interventional
Not applicable
Pittsburgh, Pennsylvania, 15213, United States
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.
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
5-minute speech task designed to induce physiological arousal in a laboratory setting.
5-minute quiet rest period.
Time frame: 5 minutes before task, and 5, 10, 20, 30, 45, 60, 75, 90 and 120 minutes after the task.
Serum levels of mitochondrial DNA assessed from blood samples
Time frame: 5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods
Plasma levels of interleukin-6
Time frame: 5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods
Plasma levels of tumor necrosis factor-alpha
Time frame: last 5 minutes of baseline, 5-min task-period, first two 5 minutes post-task.
Continuous measurement of heart rate was averaged across 4 periods: last 5 minutes of baseline, 5-min task-period, first two 5 minutes post-task.
Time frame: 5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120
Blood pressure was assessed twice on 10 occasions across the protocol. The two readings on each occasion were averaged.
Time frame: 5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120 post task onset
Diastolic blood pressure was assessed two times on 10 occasions across the protocol. On each occasion, the two measures were averaged.
Time frame: 5 minutes before to 10, 20, 30, 45, 60 minutes post-task periods
Circulating levels of cortisol assessed by ELISA
Time frame: 5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods
Levels of epinephrine in plasma
Time frame: 5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods
Levels of norepinephrine in plasma
Time frame: Pre-task, task, and 1-5 and 6-10 minutes post task
Interbeat intervals of heart rate assessed by 3-lead EKG. Measures were taken continuously from 5 minutes before the task to 10 minutes after the task. Rsults were then averaged across 4 periods: 5 minutes prior to the task, the 5-minute task period, and 5-, and 10-minutes post task
Time frame: 2 minutes before and 2, 60, and 120 minutes post-task periods
Momentary assessment of fatigue, measured as score on the fatigue subscale on the brief Profile of Mood States questionnaire. Scores range from 0 - 20, with higher scores reflecting more fatigue.
Time frame: 2 minutes before and 2-, 60-, and 120-minutes post-task periods
Momentary assessment of anger, measured as score on the anger subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more anger.
Time frame: 2 minutes before and 2-, 60- and 120-minutes post-task periods
Momentary assessment of anxious mood, measured as score on the anxiety subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more anxious mood.
Time frame: 2 minutes before and 2-, 60- and 120-minutes post-task periods
Momentary assessment of depressed mood, measured as score on the depression subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more depressed mood.
Time frame: 2 minutes before and 2-, 60-, and 120-minutes post-task periods
Momentary assessment of vigor, measured as score on the vigor subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more vigor.
Time frame: 2 minutes before and 2-, 60- and 120-minutes post-task periods
Momentary assessment of wellbeing, measured as score on the wellbeing subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more wellbeing.
Time frame: 2 minutes before and 2-, 60-, and 120-minutes post-task periods
Momentary assessment of calm mood, measured as score on the calm subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more calm mood.
University of Pittsburgh
Other
Transduction of Psychological Stress Into Systematic Inflammation by Mitochondrial DNA Signaling
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