Acute Inflammatory Response to Psychological Stress Clinical Trial
Official title:
Transduction of Psychological Stress Into Systematic Inflammation by Mitochondrial DNA Signaling
| Verified date | February 2024 |
| Source | University of Pittsburgh |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 72 |
| Est. completion date | January 31, 2022 |
| Est. primary completion date | January 31, 2022 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 20 Years to 50 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Pittsburgh | Pittsburgh | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| University of Pittsburgh | National Institute of Mental Health (NIMH) |
United States,
Trumpff C, Marsland AL, Basualto-Alarcon C, Martin JL, Carroll JE, Sturm G, Vincent AE, Mosharov EV, Gu Z, Kaufman BA, Picard M. Acute psychological stress increases serum circulating cell-free mitochondrial DNA. Psychoneuroendocrinology. 2019 Aug;106:268-276. doi: 10.1016/j.psyneuen.2019.03.026. Epub 2019 Mar 28. — View Citation
Trumpff C, Marsland AL, Sloan RP, Kaufman BA, Picard M. Predictors of ccf-mtDNA reactivity to acute psychological stress identified using machine learning classifiers: A proof-of-concept. Psychoneuroendocrinology. 2019 Sep;107:82-92. doi: 10.1016/j.psyneuen.2019.05.001. Epub 2019 May 7. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Cell-free Mitochondrial DNA | Serum levels of mitochondrial DNA assessed from blood samples | 5 minutes before task, and 5, 10, 20, 30, 45, 60, 75, 90 and 120 minutes after the task. | |
| Primary | Interleukin-6 | Plasma levels of interleukin-6 | 5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods | |
| Primary | Tumor Necrosis Factor-alpha | Plasma levels of tumor necrosis factor-alpha | 5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods | |
| Secondary | Heart Rate | 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. | last 5 minutes of baseline, 5-min task-period, first two 5 minutes post-task. | |
| Secondary | Systolic Blood Pressure | Blood pressure was assessed twice on 10 occasions across the protocol. The two readings on each occasion were averaged. | 5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120 | |
| Secondary | Diastolic Blood Pressure | Diastolic blood pressure was assessed two times on 10 occasions across the protocol. On each occasion, the two measures were averaged. | 5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120 post task onset | |
| Secondary | Cortisol | Circulating levels of cortisol assessed by ELISA | 5 minutes before to 10, 20, 30, 45, 60 minutes post-task periods | |
| Secondary | Epinephrine | Levels of epinephrine in plasma | 5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods | |
| Secondary | Norepinephrine | Levels of norepinephrine in plasma | 5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods | |
| Secondary | Heart Rate Variability | 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 | Pre-task, task, and 1-5 and 6-10 minutes post task | |
| Secondary | Fatigue | 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. | 2 minutes before and 2, 60, and 120 minutes post-task periods | |
| Secondary | Anger | 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. | 2 minutes before and 2-, 60-, and 120-minutes post-task periods | |
| Secondary | Anxious Mood | 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. | 2 minutes before and 2-, 60- and 120-minutes post-task periods | |
| Secondary | Depressed Mood | 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. | 2 minutes before and 2-, 60- and 120-minutes post-task periods | |
| Secondary | Vigor | 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. | 2 minutes before and 2-, 60-, and 120-minutes post-task periods | |
| Secondary | Wellbeing | 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. | 2 minutes before and 2-, 60- and 120-minutes post-task periods | |
| Secondary | Calm Mood | 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. | 2 minutes before and 2-, 60-, and 120-minutes post-task periods |