DNA Damage, Psychological Stress
Conditions
Brief summary
The goal of this study is to examine the impact of psychological stress on DNA integrity by conducting an experiment under controlled conditions with healthy volunteers to directly test the extent to which acute stress increases DNA damage, while simultaneously testing the blocking effects of pre-treatment with propranolol, and exploring key hypothesized mediators and moderators of the severity of the DNA damage.
Interventions
DRUGPropranolol
A single oral dose (80mg) of propranolol will be administered in a blinded capsule at the start of the baseline monitoring period of the acute stress study visit.
DRUGPlacebo oral capsule
A single blinded capsule containing no active medication will be administered at the start of the baseline monitoring period of the acute stress study visit.
BEHAVIORALAcute stress task
Participants will complete speech and arithmetic tasks, performed in front of an audience (e.g., researcher staff members) and recorded by a video camera to assess non-verbal behaviors and evaluate performance. The task will be initiated following completion of baseline sample collection during the acute stress study visit and will take approximately 15 minutes.
BEHAVIORALNo stress task
Participants will sit quietly for 5 minutes, read a short passage aloud for 5 minutes, and read a list of numbers aloud for 5 minutes. The task will be initiated following completion of baseline sample collection during the no stress study visit and will take approximately 15 minutes.
Sponsors
National Cancer Institute (NCI)
Dana Bovbjerg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 20-59 * Weigh at least 110 pounds * Fasting blood sugar below 150 mg/dL, or random blood sugar below 200 mg/dL * Thyroid stimulating hormone level between 0.25 mU/L and 6.0 mU/L * Resting blood pressure below 160/100 mm Hg * If female, have either regular menstrual periods (21-35 days) or are post-menopausal
Exclusion criteria
* Use of illicit drugs or nicotine-containing products other than cigarettes in the past month * Current alcohol abuse * Diagnosed with any of the following: cancer (other than basal cell skin cancer), chronic obstructive pulmonary disorder (COPD), multiple sclerosis (MS), severe traumatic brain injury, hypertension (high blood pressure), coronary artery disease, congestive heart failure, or other serious heart disease * Current diabetes, asthma, depression, bipolar disorder, anxiety, or schizophrenia * If female, pregnancy or breastfeeding within the past 3 months * If female, taking any medications that prevent monthly menstrual cycles (e.g., birth control shot, IUD, seasonal birth control) * Resting systolic blood pressure of \< 90 mm Hg or resting pulse \< 50 beats per minute
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DNA Stress Response | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute acute stress task period | Change in percent tail intensity will be measured using the Comet assay of DNA damage in blood samples |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DNA Stress Response (γ-H2AX) | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute task period | Change in cellular γ-H2AX levels will be measured in blood samples |
| Neuroendocrine Stress Response (Norepinephrine (NE)) | Blood samples will be collected after a 60 minute baseline period and during/after the approximately 15 minute task period | Change in circulating plasma NE levels will be measured in blood samples |
| Neuroendocrine Stress Response (Epinephrine (EPI)) | Blood samples will be collected after a 60 minute baseline period and during/after the approximately 15 minute task period | Change in circulating plasma EPI levels will be measured in blood samples |
| Hematological Stress Response | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute task period | Change in the white blood cell populations present in blood samples will be measured through complete blood count with differential analysis and flow cytometry |
| DNA Stress Response (8-OHdG) | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute task period | Change in DNA 8-OHdG levels will be measured in blood samples |
| Cardiovascular Stress Response (Systolic blood pressure (SBP)) | Blood pressure will be assessed throughout the 60 minute baseline period and during/after the approximately 15 minute task period | Change in SBP/DBP will be calculated from repeated assessments |
| Cardiovascular Stress Response (Diastolic blood pressure (DBP)) | Blood pressure will be assessed throughout the 60 minute baseline period and during/after the approximately 15 minute task period | Change in DBP will be calculated from repeated assessments |
| Psychological Stress Response (Anxiety Visual Analogue Scale (VAS)) | Anxiety VAS will be administered after a 60 minute baseline period and during/after completion of the tasks | Change in anxiety levels will be assessed by self-report measure (VAS) on a 0 to 100 scale, where 0 indicates not feeling anxious and 100 indicates feeling highly anxious |
| Psychological Stress Response (Stress Visual Analogue Scale (VAS)) | Stress VAS will be administered after a 60 minute baseline period and during/after completion of the tasks | Change in stress levels will be assessed by self-report measure (VAS) on a 0 to 100 scale, where 0 indicates not feeling stressed and 100 indicates feeling highly stressed |
| Cardiovascular Stress Response (Heart rate (HR)) | HR will be assessed throughout the 60 minute baseline period and during/after the approximately 15 minute task period | Change in HR will be calculated from repeated assessments |
Countries
United States
Outcome results
None listed