Cerebrovascular Health and Resilience in Midlife (CHARM)

This study examines cardiovascular responses to a brief psychological challenge under laboratory conditions among adult volunteers. The study volunteers are asked to complete two study sessions. In one session, the volunteers are asked to provide demographic and health-related information via questionnaires and an interview. In that session, volunteers would then be asked to undergo evaluations of their body composition, blood pressure, heart rate, and other signs of cardiovascular function and health. Lastly, volunteers would be asked to take part in a brief and challenging psychological task after a period of rest while cardiovascular activity is measured. In the other session, volunteers are asked to undergo magnetic resonance imaging and to complete neuropsychological tests of memory, attention, and processing speed. In addition to these two sessions, volunteers are asked to complete online questionnaires. The study is designed to examine associations between transient changes in cardiovascular activity induced by the psychological task, measures of overall cardiovascular health, and measures of cerebrovascular health measured by magnetic resonance imaging. Study results are expected to provide new information about the relationships between cardiovascular activity changes to psychological challenges and cardiovascular and cerebrovascular health in adults.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Cerebrovascular Disorders; Psychological Stress
• Intervention / Treatment: Behavioral: Paced Auditory Serial Addition Task

Detailed Description

This cross-sectional study examines the extent to which cardiovascular responses to the acute experience of psychological stress relate to signs of cerebrovascular health detected on magnetic resonance imaging. Study volunteers will include midlife adults who do not report having a history of clinical cardiovascular disease or dementia. Study volunteers will be asked to complete protocols to assess: behavioral, social, and biological correlates of cardiovascular and cerebrovascular health; arterial stiffness, endothelial function, and beat-to-beat blood pressure; cardiovascular changes to acute psychological stress; signs of cerebrovascular health; and, neuropsychological test performance. Cardiovascular responses to acute psychological stress will be examined in relation to indicators of brain function and structure, as well as indicators of cardiac and vascular function. Study results may help to increase knowledge about stress-related factors and cardiovascular sources of brain health.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter J Gianaros, PhD; Phone Number: 412-624-4500; Email: bnl@pitt.edu
• Study Contact Backup: Name: Sara Boyko, BS; Phone Number: 412-648-9047; Email: bnl@pitt.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Sara Boyko, BS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Able to attend 2 study visits at the University of Pittsburgh campus in Oakland (Pennsylvania)
• Able to read and speak English

Exclusion Criteria:

• Uncontrolled hypertension (systolic blood pressure >160 or diastolic blood pressure >100 mmHg)
• Current use of anticonvulsant, anti-Parkinson, neuroleptic, or antipsychotic medications
• Current use of glucocorticoids (e.g., oral prednisone) or ephedrine
• Current chronic conditions of the lungs, liver and kidney, as well as cancer (chemotherapy and radiation) treatment in the past 12 months (allowances are made for non-melanoma skin cancer treatment, controlled asthma, and allergy inhalers)
• Self-reported major neurological disorders or brain injuries (e.g., multiple sclerosis, cerebral palsy, major head injury)
• Self-reported psychotic illnesses (mania, bipolar disorder, schizophrenia)
• Current pregnancy or childbirth within the past 6 months
• Suspected mild cognitive impairment or dementia
• Self reported sleep apnea
• Self-reported history of myocardial infarction, stroke, or revascularization procedures, as well as treatment for cardiac arrhythmias
• Self-reported lack of comfort to undergo MRI testing
• Presence of implants or objects that are unsafe for MRI (e.g., tattooed eyeliner), as well as any other contraindications that would prevent MRI testing
• Self-reported lack of comfort to undergo the laboratory math task

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Paced Auditory Serial Addition Task; For the Paced Auditory Serial Addition Task, volunteers are presented with single digit numbers (1-9), and are instructed to add any given number to the previously presented number, and call out the answer. Volunteers are told that their performance is being monitored by research assistants. Volunteers are provided with a signaling device that they can use to discontinue testing. Lastly, participants will be asked to complete brief questionnaires to assess their levels of experienced threat, challenge, valence, arousal, and sense of control.

Behavioral: Paced Auditory Serial Addition Task; Study volunteers will be asked to complete a 4-minute Paced Auditory Serial Addition Task, which is a standardized task that is widely used to study cardiovascular responses to acute psychological challenges (or stressors) in a laboratory setting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in systolic blood pressure (SBP) from baseline to task	The mean SBP from the baseline period will be subtracted from the mean of the task period.	Mean SBPs for the computation of change scores will be computed from the average of the 5 min baseline period and average of the 4 min task period
White matter hyperintensity burden	White matter hyperintensity burden will be computed as the total sum of the voxels segmented as hyperintensities multiplied by voxel dimensions to yield a total score (units of mm-cubed).	Derived from one acquisition sequence within in a 50 min multimodal MRI protocol
Hippocampal volume	Total bilateral hippocampal volume will be computed as the total sum of voxels automatically segmented.	Derived from one acquisition sequence within a 50 min multimodal MRI protocol
Perivascular space volume	Total perivascular space volume will be computed from segmented brain blood vessel-tissue interfaces.	Derived from one acquisition sequence in a 50 min multimodal MRI protocol
Pulse wave velocity	Pulse wave velocity in m/s will be assessed by dual impedance cardiography as a non-invasive indicator of arterial stiffness. This measure will be derived from the 5 minute baseline period.	5 minutes
Spontaneous baroreflex sensitivity	Spontaneous baroreflex sensitivity in ms/mmHg will be computed by the sequence method applied to beat-to-beat blood pressure and electrocardiogram recordings.	5 minutes
Endothelial function	Endothelial-dependent vasodilation will be measured non-invasively in a reactive hyperemia protocol using digital thermal monitoring.	15 minutes

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Peter J Gianaros, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2023
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Behavioral Symptoms; Behavior; Cardiovascular Diseases; Cerebrovascular Disorders; Stress, Psychological
• Other Study ID Numbers: STUDY23030073; R01HL169990 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data that comprise primary and secondary study outcomes will be made available with data dictionaries via the University of Pittsburgh's repository, D-Scholarship@Pitt. This repository provides indefinite storage and accessibility. Along with de-identified data, other shared resources will include a description of data collection methods and study code book; a description of the data files; and descriptions of data use conditions. Statistical scripts will be deposited as appropriate following publication of manuscripts bearing on the aims of the study. All publications will include information on the location of study data and accessibility. Requests by researchers for other de-identified data will be facilitated by completion of a Data Use Agreement, as well as provision of a methodologically sound proposal and approval from their institution.
• IPD Sharing Time Frame: Data are anticipated to become available within 12 months after the publication of findings bearing on the Specific Aims of R01HL169990
• IPD Sharing Access Criteria: All presentations and publications will include information on the location of study data and its public accessibility for research use. The criteria for certain requests of de-identified data will involve the completion of a Data Use Agreement, https://www.osp.pitt.edu/osp-teams/clinical-corporate-contract-services/negotiations/data-use-agreements-duas
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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