Psychological Challenges for Cardiovascular Health

(CHARM Trial)

Overseen By Sara Boyko, BS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Anticonvulsants, Antipsychotics, Glucocorticoids, Ephedrine

Disqualifiers: Hypertension, Neurological disorders, Psychotic illnesses, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the heart and blood vessels respond to challenging mental tasks. The goal is to identify connections between these responses and overall heart and brain health. Participants will complete a math challenge called the Paced Auditory Serial Addition Task (PASAT) while researchers monitor heart activity. They will also undergo memory and attention tests during an MRI scan. This trial may suit adults who can attend sessions in Pittsburgh and are comfortable with MRI scans and simple math tasks. As an unphased study, it offers a unique opportunity to contribute to important research on heart and brain health.

Will I have to stop taking my current medications?

The trial requires that you do not currently use certain medications, such as anticonvulsants, anti-Parkinson drugs, neuroleptics, antipsychotics, glucocorticoids, or ephedrine. If you are taking any of these, you would need to stop before participating.

What prior data suggests that this psychological challenge is safe for cardiovascular health studies?

Research shows that the Paced Auditory Serial Addition Task (PASAT) can induce stress and alter heart activity. Studies have found that participants often experience increased stress while performing the task, typically accompanied by changes in heart rate and blood pressure. Designed to test attention, the task naturally causes some stress. However, these changes are temporary. Participants receive monitoring during the task and can stop if they feel uncomfortable. Overall, these studies consider the task safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Paced Auditory Serial Addition Task because it explores the psychological factors affecting cardiovascular health, an area not typically addressed by standard treatments like medication or lifestyle changes. This task challenges participants cognitively by having them add numbers in a sequence, which could reveal how mental stress impacts heart health. By understanding these connections, the trial could open new avenues for managing cardiovascular conditions through psychological interventions, offering a complementary approach to traditional methods.

What evidence suggests that the Paced Auditory Serial Addition Task is effective for assessing cardiovascular responses to psychological challenges?

Research shows that the Paced Auditory Serial Addition Task (PASAT), which participants in this trial will undertake, affects heart rate and blood pressure. Studies have found that both usually rise during the task, indicating a connection between the task and heart activity. In one study, levels of IL-6, linked to inflammation, increased after the task, highlighting its role in stress response. Additionally, people often report feeling more stressed after completing the PASAT. These findings suggest that the task effectively triggers noticeable heart and stress responses, which are important for understanding the link between heart and brain health. ^{1 5 6 7 8}

Who Is on the Research Team?

Peter J Gianaros, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults who can visit the University of Pittsburgh twice, speak English, and have stable blood pressure. It's not for those with certain neurological disorders, recent major heart issues or surgeries, current pregnancy or childbirth within six months, use of specific medications like anticonvulsants or glucocorticoids, severe lung/liver/kidney diseases including cancer treatment in the past year (except non-melanoma skin cancer), mental health conditions like bipolar disorder or schizophrenia, discomfort with math tasks or MRI tests, sleep apnea diagnosis, and those with MRI-unsafe implants.

Inclusion Criteria

I can go to the University of Pittsburgh in Oakland for 2 study visits.

Exclusion Criteria

I may have mild memory loss or dementia.

Current pregnancy or childbirth within the past 6 months

You don't feel comfortable doing the math task in the lab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Session 1

Participants provide demographic and health-related information, undergo evaluations of body composition, blood pressure, heart rate, and participate in a psychological task

1 day

1 visit (in-person)

Session 2

Participants undergo magnetic resonance imaging and complete neuropsychological tests of memory, attention, and processing speed

1 day

1 visit (in-person)

Follow-up

Participants complete online questionnaires to assess various psychological and health-related factors

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Paced Auditory Serial Addition Task

Trial Overview The study investigates how adult volunteers' cardiovascular systems respond to a psychological challenge. Participants will provide health information and undergo body composition assessments along with monitoring of blood pressure and heart rate. They'll also perform a challenging psychological task while their cardiovascular activity is measured. Additionally, they'll have an MRI scan and complete cognitive tests to explore links between cardiovascular responses to stressors and overall cerebrovascular health.

How Is the Trial Designed?

Group I: Paced Auditory Serial Addition Task Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The study reviews the reliability and validity of various mental stress tests in cardiovascular research, categorizing them into five types and emphasizing the importance of selecting appropriate tests based on practical and theoretical criteria.

Analysis of cardiovascular responses to mental stress tests showed that heart rate and blood pressure reactions are relatively stable over time, with heart rate showing the strongest test-retest correlation, indicating that these tests can be reliable measures for assessing cardiovascular responses to mental stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodology of mental stress testing in cardiovascular research. Steptoe, A., Vögele, C.[2008]

The new experimental stress protocol effectively induced significant stress responses in 32 healthy males, showing high test-retest stability for neuroendocrine and cardiovascular measures, which is important for future studies on stress reactivity.

Participants exhibited lower cortisol and subjective stress responses during the second exposure, indicating possible habituation or learning effects, while their performance on the cognitive task improved, suggesting the protocol's potential for repeated measures in research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Test-retest reproducibility of a combined physical and cognitive stressor. Bachmann, P., Finke, JB., Rebeck, D., et al.[2020]

In a study with 15 participants, faster rates of the Paced Auditory Serial Addition Task (PASAT) led to decreased accuracy in responses and increased self-reported stress levels, highlighting the task's impact on cognitive load and stress.

The autonomic responses, such as changes in heart rate and blood pressure, were significantly different when comparing the slowest PASAT (3.6 seconds) to faster rates, suggesting that a standardized PASAT rate could be crucial for accurately assessing stress and autonomic nervous system function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the Paced Auditory Serial Addition Task (PASAT) with different rates on autonomic nervous system responses and self-reported levels of stress. Tanosoto, T., Bendixen, KH., Arima, T., et al.[2015]

In a study of 22 healthy adults, cardiovascular responses varied significantly between mental arithmetic stress and cold pressor stress, with mental arithmetic eliciting specific changes in T-wave amplitude and left ventricular ejection time.

Both stressors increased inter-beat intervals and subjective stress ratings, but mental arithmetic caused a more intense response, suggesting that cognitive processing level influences cardiovascular reactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential beta- and alpha-adrenergic activation during psychological stress. Montoya, P., Brody, S., Beck, K., et al.[2019]

Blunted cardiovascular reactions to stress are linked to negative health outcomes, including increased risk of cardiovascular issues like myocardial infarction and behavioral problems such as obesity and depression, based on a review of 23 studies.

Specific thresholds for blunted cardiovascular reactivity were identified, with heart rate reductions of -3.00 to 12.59 bpm and blood pressure drops of -2.4 to 5.00 mmHg indicating higher risk, suggesting these measures could help clinicians identify at-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blunted cardiovascular reactivity to psychological stress and prospective health: a systematic review. O' Riordan, A., Howard, S., Gallagher, S.[2023]

In a study of 60 healthy young men, those with high casual systolic pressure exhibited significantly greater increases in blood pressure and heart rate during challenging tasks compared to those with normal pressure, indicating heightened cardiovascular reactivity under stress.

The choice of task difficulty influenced cardiovascular responses, with individuals who opted for more difficult tasks showing greater increases in systolic pressure and heart rate, suggesting that psychological factors like fear of failure can impact cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory reactivity assessment: effects of casual blood pressure status and choice of task difficulty. Sherwood, A., Royal, SA., Light, KC.[2019]

In a study of 566 healthy North American adults using a modified 200-item Paced Auditory Serial Addition Task (PASAT), age, education, and ethnicity were found to significantly influence test performance, explaining nearly 23% of the variance.

The research provides a formula and tables for calculating age, education, and ethnicity-adjusted T scores, which can help in accurately interpreting PASAT results in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Paced Auditory Serial Addition Task (PASAT): norms for age, education, and ethnicity. Diehr, MC., Heaton, RK., Miller, W., et al.[2022]

Vocal delivery of responses during mental arithmetic tasks increased subjective distress and negatively impacted performance, while also raising diastolic blood pressure.

Different types of noise distractions heightened distress levels but did not affect task performance, indicating that while distractions can increase stress, they may not necessarily hinder cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What do arithmetic stress tests measure? Protocol variations and cardiovascular responses. Linden, W.[2019]

In a study involving 80 healthy male students, social challenges during discussions caused significant increases in systolic blood pressure (SBP) and heart rate (HR), indicating a strong cardiovascular response to social stress.

Monetary incentives were found to enhance heart rate reactivity during these challenges, suggesting that external rewards can influence how our bodies respond to stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiovascular effects of active coping behavior in mental and social stress situations during various incentive conditions]. Gramer, M., Huber, HP.[2006]

The Paced Auditory Serial Opposites Task (PASOT) was developed as a less anxiety-inducing alternative to the Paced Auditory Serial Addition Task (PASAT), showing a strong correlation (0.71) in cognitive assessment between the two tasks among 40 participants.

Participants reported significantly lower levels of negative feelings and anxiety while performing the PASOT compared to the PASAT, indicating that PASOT may be a more suitable option for assessing attention and concentration without inducing stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is the PASAT past it? Testing attention and concentration without numbers. Gow, AJ., Deary, IJ.[2008]

In a study with 20 healthy male subjects, those who chose a 'difficult' mental arithmetic task exhibited significantly greater cardiovascular responses, including increased myocardial contractility and systolic blood pressure, compared to those who chose an 'easy' task.

The study suggests that allowing individuals to choose the difficulty of tasks may enhance the ecological validity of laboratory assessments of cardiovascular reactivity, although the findings are considered provocative and not definitive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular reactivity assessment: effects of choice of difficulty on laboratory task responses. Sherwood, A., Davis, MR., Dolan, CA., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11801429/

Inflammatory and Cardiovascular Responses to Active and ... Active Stress Task: Paced Auditory Serial Addition Task. An 8-minute version of the Paced Auditory Serial Addition Task (PASAT) (46) was used ...

2. journals.lww.com journals.lww.com/bsam/fulltext/2025/02000/inflammatory_and_cardiovascular_responses_to.3.aspx

Inflammatory and Cardiovascular Responses to Active and... Cardiovascular measures were higher during the PASAT than IAPS (p < .001). Circulating IL-6 levels increased from baseline to 45-minutes after both tasks (p ≤ .

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/psyp.13707

Blunted cardiovascular reactivity to acute psychological ... This study found that low Paced Auditory Serial Addition Test (PASAT) systolic blood pressure (SBP) and diastolic blood pressure (DBP) ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25495065/

Effects of the Paced Auditory Serial Addition Task (PASAT ... Increased PASAT rates were associated with decreases in correct responses (P < 0·001) and increases in self-reported levels of stress (P < 0·001).

5. eprints.lib.hokudai.ac.jp eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/61460/1/JOR42%285%29.pdf

Effects of the Paced Auditory Serial Addition Task (PASAT) ... Our results are in accordance with a previous finding that heart rate and blood pressure values were relatively constant across the four different rates of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9541813/

Cardiovascular reactions to acute psychological stress and ... Participants completed the Paced Auditory Serial Addition Task (PASAT; Gronwall,), which has been shown to significantly perturb cardiovascular ...

7. taylorandfrancis.com taylorandfrancis.com/knowledge/Medicine_and_healthcare/Psychiatry/Paced_auditory_serial_addition_test/

Paced auditory serial addition test The Paced Auditory Serial Addition Test (PASAT) is a cognitive assessment tool that evaluates sustained and divided attention.

8. researchgate.net researchgate.net/publication/269418926_Effects_of_the_Paced_Auditory_Serial_Addition_Task_PASAT_with_different_rates_on_autonomic_nervous_system_responses_and_self-reported_levels_of_stress

Effects of the Paced Auditory Serial Addition Task (PASAT ... Results Perceived level of distress was highest for the mental stress task compared to no task (p < 0.001) and neutral task conditions (p = ...