Brief Stresses Experimental Study

Brief Stresses and DNA Integrity: An Experimental Analysis

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.

Study Overview

• Status: Terminated
• Conditions: DNA Damage; Psychological Stress
• Intervention / Treatment: Drug: Propranolol; Behavioral: Acute stress task; Behavioral: No stress task; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dana Bovbjerg
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Dana Bovbjerg, PhD, University of Pittsburgh; Principal Investigator: Frank Jenkins, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2017
• Primary Completion (Actual): January 27, 2022
• Study Completion (Actual): January 27, 2022

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Stress, Psychological; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: PRO16080092; R01CA211371 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No