Neurocardiac Interactions Evaluated by Anatomic and Physiologic MRI Assessment

NCT ID: NCT02962154

Last Updated: 2018-01-09

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2018-01-31

Brief Summary

The purpose of project is to answer fundamental questions about the mechanisms underlying mental stress ischemia in patients with coronary artery disease, mood disorders, or both, and to identify potential biomarkers and psychosocial risk factors associated with this condition.

To achieve this goal, investigators will use cutting-edge cardiovascular and functional neuroimaging tools to study mental stress ischemia in a carefully controlled laboratory setting in subjects recruited from four patient populations: 1) patients who recently sustained a myocardial infarction; 2) patients undergoing non-emergent invasive coronary angiography (with and without known coronary artery disease); 3) patients with a diagnosis of major depressive disorder; and 4) patients with a diagnosis of bipolar 1 or bipolar 2 disorder.

Detailed Description

Mental stress ischemia occurs when a psychosocial or mental stressor triggers an imbalance between the supply and demand for oxygen by cardiac myocytes. Epidemiological studies indicate that mental stress ischemia is common, occurring in 20-25% of patients with coronary artery disease (CAD) and portends a poor prognosis. The underlying mechanisms are thought to involve stress-induced activation of the sympathetic nervous system and associated effects on cardiovascular function. But how neurobiological and cardiovascular factors interact to generate mental stress ischemia is unknown. Furthermore, patients with major depressive disorder, bipolar disorder, and other stress-related psychiatric conditions have elevated rates of cardiovascular co-morbidities, including sudden cardiac death, yet mental stress ischemia has not been studied extensively in these psychiatric populations. The purpose of project is to answer fundamental questions about the mechanisms underlying mental stress ischemia in patients with coronary artery disease, mood disorders, or both, and to identify potential biomarkers and psychosocial risk factors associated with this condition.

To achieve this goal, investigators will use cutting-edge cardiovascular and functional neuroimaging tools to study mental stress ischemia in a carefully controlled laboratory setting in subjects recruited from four patient populations: 1) patients who recently sustained a myocardial infarction; 2) patients undergoing non-emergent invasive coronary angiography (with and without known coronary artery disease); 3) patients with a diagnosis of major depressive disorder; and 4) patients with a diagnosis of bipolar 1 or bipolar 2 disorder.

Conditions

Ischemia; Stress, Mental

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Coronary Artery Disease (CAD)

Patients with known coronary artery disease (CAD) as defined by prior PCI, CABG, prior MI, prior abnormal stress test, or invasive coronary angiography (ICA) and who are hemodynamically stable

They will undergo the following:

Radiation: Coronary CT Angiography Other: Mood Symptom Scale Other: Anxiety Symptom Scale Other: Chronic Stress Inventories Other: Psychosocial Function Questionnaires Other: General Health and quality of life questionnaires Other: Magnetic Resonance Imaging

Coronary CT Angiography

Intervention Type: RADIATION

The coronary CT angiography will assess for coronary artery stenosis, plaque characteristics, calcifications, and other factors.

Mood Symptom Scale

Intervention Type: OTHER

Some or all of the following questionnaires will be conducted to assess mood symptoms:

Beck Depression Inventory, Hamilton Depression Rating Scale (24-item), Montgomery Asberg Depression Rating Scale (MADRS), Mood and Anxiety Symptom Questionnaire (MASQ), QIDS, Young Mania Rating Scale

Anxiety Symptom Scale

Intervention Type: OTHER

Some or all of the following questionnaires will be conducted to assess anxiety symptoms:

Beck Anxiety Inventory, Spielberger State/Trait Anxiety Inventory (STAI), GAD-7 Anxiety Questionnaire, Penn State Worry Questionnaire (PSWQ)

Chronic Stress Inventories

Intervention Type: OTHER

Some of all of the following questionnaires will be conducted to assess chronic stress:

Chronic stress inventories: Cohen Perceived Stress Scale, Holmes and Rahe Stressful Life Events Scale, Karasek Job Strain Questionnaire, Conner-Davidson Resilience Scale, PTSD Checklist

Psychosocial Function Questionnaires

Intervention Type: OTHER

Some of all of the following questionnaires will be conducted to assess psychosocial function:

Type A Personality Scale, NEO Personality Inventory, Positive and Negative Affect Schedule (PANAS), Behavioral Inhibition/Behavioral Approach Scale (BIS/BAS)

General Health and quality of life questionnaires

Intervention Type: OTHER

Some of all of the following questionnaires will be conducted to assess quality of life:

EQ-5D Health Questionnaire, Seattle Angina Questionnaire, International Index of Erectile Function (ILEF-5), Pittsburgh Sleep Quality Scale, Morningness Eveningness Questionnaire

Magnetic Resonance Imaging

Intervention Type: OTHER

First, subjects will undergo a resting cardiac MR perfusion study to establish baseline (pre-stress) measures of cardiovascular function. Second, subjects will undergo a series of brain magnetic resonance imaging studies (T1-weighted anatomical MRI, diffusion tensor imaging, resting state functional MRI) to establish baseline (pre-stress) measures of brain function and structural correlates. Third, investigators will use a well-validated cognitive task to induce mental stress by testing subjects' working memory for a series of emotionally arousing or neutral images, while repeating the functional MRI scan. Finally, subjects will undergo a repeat cardiac MR perfusion study while being tested on the same mental stress task.

Major Depressive Disorder

Patients with a diagnosis of major depressive disorder and/or a diagnosis of bipolar 1 or bipolar 2 disorder

They will undergo the following:

Radiation: Coronary CT Angiography Other: Mood Symptom Scale Other: Anxiety Symptom Scale Other: Chronic Stress Inventories Other: Psychosocial Function Questionnaires Other: General Health and quality of life questionnaires Other: Magnetic Resonance Imaging

Coronary CT Angiography

Intervention Type: RADIATION

The coronary CT angiography will assess for coronary artery stenosis, plaque characteristics, calcifications, and other factors.

Mood Symptom Scale

Intervention Type: OTHER

Some or all of the following questionnaires will be conducted to assess mood symptoms:

Beck Depression Inventory, Hamilton Depression Rating Scale (24-item), Montgomery Asberg Depression Rating Scale (MADRS), Mood and Anxiety Symptom Questionnaire (MASQ), QIDS, Young Mania Rating Scale

Anxiety Symptom Scale

Intervention Type: OTHER

Some or all of the following questionnaires will be conducted to assess anxiety symptoms:

Beck Anxiety Inventory, Spielberger State/Trait Anxiety Inventory (STAI), GAD-7 Anxiety Questionnaire, Penn State Worry Questionnaire (PSWQ)

Chronic Stress Inventories

Intervention Type: OTHER

Some of all of the following questionnaires will be conducted to assess chronic stress:

Chronic stress inventories: Cohen Perceived Stress Scale, Holmes and Rahe Stressful Life Events Scale, Karasek Job Strain Questionnaire, Conner-Davidson Resilience Scale, PTSD Checklist

Psychosocial Function Questionnaires

Intervention Type: OTHER

Some of all of the following questionnaires will be conducted to assess psychosocial function:

Type A Personality Scale, NEO Personality Inventory, Positive and Negative Affect Schedule (PANAS), Behavioral Inhibition/Behavioral Approach Scale (BIS/BAS)

General Health and quality of life questionnaires

Intervention Type: OTHER

Some of all of the following questionnaires will be conducted to assess quality of life:

EQ-5D Health Questionnaire, Seattle Angina Questionnaire, International Index of Erectile Function (ILEF-5), Pittsburgh Sleep Quality Scale, Morningness Eveningness Questionnaire

Magnetic Resonance Imaging

Intervention Type: OTHER

First, subjects will undergo a resting cardiac MR perfusion study to establish baseline (pre-stress) measures of cardiovascular function. Second, subjects will undergo a series of brain magnetic resonance imaging studies (T1-weighted anatomical MRI, diffusion tensor imaging, resting state functional MRI) to establish baseline (pre-stress) measures of brain function and structural correlates. Third, investigators will use a well-validated cognitive task to induce mental stress by testing subjects' working memory for a series of emotionally arousing or neutral images, while repeating the functional MRI scan. Finally, subjects will undergo a repeat cardiac MR perfusion study while being tested on the same mental stress task.

Interventions

Coronary CT Angiography

The coronary CT angiography will assess for coronary artery stenosis, plaque characteristics, calcifications, and other factors.

Intervention Type: RADIATION

Mood Symptom Scale

Some or all of the following questionnaires will be conducted to assess mood symptoms:

Beck Depression Inventory, Hamilton Depression Rating Scale (24-item), Montgomery Asberg Depression Rating Scale (MADRS), Mood and Anxiety Symptom Questionnaire (MASQ), QIDS, Young Mania Rating Scale

Intervention Type: OTHER

Anxiety Symptom Scale

Some or all of the following questionnaires will be conducted to assess anxiety symptoms:

Beck Anxiety Inventory, Spielberger State/Trait Anxiety Inventory (STAI), GAD-7 Anxiety Questionnaire, Penn State Worry Questionnaire (PSWQ)

Intervention Type: OTHER

Chronic Stress Inventories

Some of all of the following questionnaires will be conducted to assess chronic stress:

Chronic stress inventories: Cohen Perceived Stress Scale, Holmes and Rahe Stressful Life Events Scale, Karasek Job Strain Questionnaire, Conner-Davidson Resilience Scale, PTSD Checklist

Intervention Type: OTHER

Psychosocial Function Questionnaires

Some of all of the following questionnaires will be conducted to assess psychosocial function:

Type A Personality Scale, NEO Personality Inventory, Positive and Negative Affect Schedule (PANAS), Behavioral Inhibition/Behavioral Approach Scale (BIS/BAS)

Intervention Type: OTHER

General Health and quality of life questionnaires

Some of all of the following questionnaires will be conducted to assess quality of life:

EQ-5D Health Questionnaire, Seattle Angina Questionnaire, International Index of Erectile Function (ILEF-5), Pittsburgh Sleep Quality Scale, Morningness Eveningness Questionnaire

Intervention Type: OTHER

Magnetic Resonance Imaging

First, subjects will undergo a resting cardiac MR perfusion study to establish baseline (pre-stress) measures of cardiovascular function. Second, subjects will undergo a series of brain magnetic resonance imaging studies (T1-weighted anatomical MRI, diffusion tensor imaging, resting state functional MRI) to establish baseline (pre-stress) measures of brain function and structural correlates. Third, investigators will use a well-validated cognitive task to induce mental stress by testing subjects' working memory for a series of emotionally arousing or neutral images, while repeating the functional MRI scan. Finally, subjects will undergo a repeat cardiac MR perfusion study while being tested on the same mental stress task.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male and female subjects, ages 50 years or more

2. Able to provide informed consent. Must be fluent english speakers.

3. Known coronary artery disease (CAD) as defined by prior PCI, CABG, prior MI, prior abnormal stress test or invasive coronary angiography (ICA)

4. Patients that are hemodynamically stable

1. Male and female subjects, ages 50 years or more

2. Must be fluent English-speakers due to the design of the mental stress tasks. Able to provide informed consent.

3. Subjects who are stable and meet DSM-V criteria for a diagnosis of major depressive disorder, bipolar 1 disorder, or bipolar 2 disorder, as assessed in an initial screening interview by phone and confirmed by a structured clinical interview on the first day of the study.

Exclusion Criteria

1. Evidence of ongoing myocardial infarction or homonymic instability

2. Positive pregnancy test or unknown pregnant state at the time of enrollment for all women of child-bearing potential

3. Known contraindications to cardiovascular CT angiography with intravenous contrast (A) Known allergies (B) Renal dysfunction (GFR < 30ml/min) (C) Contraindications to beta-blockers or nitroglycerin or adenosine (D) Irregular heart rate not controlled by administration of beta-blockers

4. Patients with contraindications to MRI scans (A) Non-MR compatible device or material implant (B) Known allergies to gadolinium containing contrast agent (C) Renal dysfunction (GFR < 30 ml/min)

1. Subjects with a history of seizure disorder, stroke, Parkinson's disease, any form of dementia, or head injury resulting in loss of consciousness will be excluded from this study.

3. Subjects who indicate that there is a chance that they may be pregnant will be asked to take a pregnancy test. They will be informed of the potential for false positive results due to diet, vitamins, and supplements, or over-the-counter medications. A positive pregnancy test will necessitate exclusion from the study, and the results will be disclosed to the participant.

4. Patients who are currently being treated with a beta blocker or daily (standing) benzodiazepines will be excluded, unless, in the judgment of the prescribing physician, the dose can be withheld on the morning of the each study session, due to the potential for these medications to mask neurobiological and cardiovascular responses to mental stress.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James K Min, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Countries

United States

Other Identifiers

1405015093

Identifier Type: -

Identifier Source: org_study_id