Brief Stresses Experimental Study

Study Overview
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Brief Summary
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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.

Official Title
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Brief Stresses and DNA Integrity: An Experimental Analysis

Conditions
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DNA Damage, Psychological Stress

Intervention / Treatment
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* Drug: Propranolol
* Drug: Placebo oral capsule
* Behavioral: Acute stress task
* Behavioral: No stress task


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propranolol group<br>This group will receive a single oral dose (80mg) of propranolol in a blinded capsule during their acute stress study visit. | Drug: Propranolol<br>* 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.<br>Behavioral: Acute stress task<br>* 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.<br>Behavioral: No stress task<br>* 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.<br>|
| Placebo Comparator: Placebo group<br>This group will receive a single blinded capsule containing no active medication during their acute stress study visit. | Drug: Placebo oral capsule<br>* 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.<br>Behavioral: Acute stress task<br>* 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.<br>Behavioral: No stress task<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA Stress Response | Change in percent tail intensity will be measured using the Comet assay of DNA damage in blood samples | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute acute stress task period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA Stress Response (8-OHdG) | Change in DNA 8-OHdG levels will be measured in blood samples | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute task period | 
| DNA Stress Response (γ-H2AX) | Change in cellular γ-H2AX levels will be measured in blood samples | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute task period | 
| Neuroendocrine Stress Response (Norepinephrine (NE)) | Change in circulating plasma NE levels will be measured in blood samples | Blood samples will be collected after a 60 minute baseline period and during/after the approximately 15 minute task period | 
| Neuroendocrine Stress Response (Epinephrine (EPI)) | Change in circulating plasma EPI levels will be measured in blood samples | Blood samples will be collected after a 60 minute baseline period and during/after the approximately 15 minute task period | 
| Hematological Stress Response | Change in the white blood cell populations present in blood samples will be measured through complete blood count with differential analysis and flow cytometry | Blood samples will be collected after a 60 minute baseline period and after the approximately 15 minute task period | 
| Cardiovascular Stress Response (Heart rate (HR)) | Change in HR will be calculated from repeated assessments | HR will be assessed throughout the 60 minute baseline period and during/after the approximately 15 minute task period | 
| Cardiovascular Stress Response (Systolic blood pressure (SBP)) | Change in SBP/DBP will be calculated from repeated assessments | Blood pressure will be assessed throughout the 60 minute baseline period and during/after the approximately 15 minute task period | 
| Cardiovascular Stress Response (Diastolic blood pressure (DBP)) | Change in DBP will be calculated from repeated assessments | Blood pressure will be assessed throughout the 60 minute baseline period and during/after the approximately 15 minute task period | 
| Psychological Stress Response (Anxiety Visual Analogue Scale (VAS)) | 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 | Anxiety VAS will be administered after a 60 minute baseline period and during/after completion of the tasks | 
| Psychological Stress Response (Stress Visual Analogue Scale (VAS)) | 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 | Stress VAS will be administered after a 60 minute baseline period and during/after completion of the tasks |