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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL085704-01 | U.S. NIH Grant/Contract | View source | |
| 8640-07-8R1ER | Other Identifier | Duke legacy protocol number |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Depression is commonly seen in patients with cardiovascular disorders. In recent studies it has been shown that mild to moderate depression symptoms were associated with increased likelihood of mental stress-induced myocardial ischemia (MSIMI), which is a risk factor of poor cardiac outcome. In this project, the investigators aim to assess the treatment of mental stress-induced myocardial ischemia in ischemic heart disease patients with mild to moderate depressive symptoms. This study is a six-week double-blind placebo controlled study to examine the effects of escitalopram on mental stress-induced myocardial ischemia. This study will look to show that patients with ischemic heart disease who are treated with escitalopram will exhibit a significant improvement of MSIMI at the end of week 6 compared to patients receiving placebo.
The goals of this project are to investigate the response of mental stress-induced myocardial ischemia (MSIMI) to escitalopram, a selective serotonin reuptake inhibitor (SSRI); to determine whether MSIMI will be reduced by the treatment, and whether the modification of MSIMI is related to improvement of depression symptoms, and/or the reduction of platelet aggregation, and/or the reduction of cardiovascular reactivity. This is a randomized study using escitalopram versus placebo for stable ischemic heart disease patients with MSIMI. This study will also explore the role of platelet activity in occurrence with MSIMI and other characteristics of MSIMI, such as systolic and diastolic function of the left ventricle during mental stress testing as compared to exercise testing.
The stress testing will be conducted at the Duke Cardiology Diagnostic Unit Laboratory. Following a 20-minute calibration-rest period, participants will be asked to complete a series of 3 mental stress tasks. There are 3 mental stress tasks to be used for this study, i.e., (1) Mental arithmetic: during this test, patients will be asked to perform a series of serial subtractions beginning at a given number which will be different for each repeated test and will be chosen by the tester from a fixed list of various numbers, with encouragement to perform calculations as quickly as possible; (2) Public speaking with anger recall: during this test, patients will be asked to give a speech on a recent situation in which they experienced anger to an audience of observers (two to three) after 1 minute of preparation. Prior to the speech, subjects are told that their speech will be evaluated on their description of the situation, as to what happened, what they thought, felt, what they did, and what happened as a result. If they run out of things to say, the research tech will prompt them with questions to elicit more content until the three minutes are up; (3) Mirror trace: during this test, patients will be asked to outline, as quickly as possible, a star from its reflection in a mirror. Each task will last 3 minutes and there will be a 6-minute rest period between tasks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Escitalopram | Experimental | Escitalopram treatment |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Escitalopram | Drug | Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With an Absence of Mental Stress-induced Myocardial Ischemia (MSIMI) During the 3 Mental Stressors | MSIMI is defined by the following: compared to rest, 1) any development of new abnormal wall motion; 2) reduction of LVEF 8% and/or; 3) deviation (depression or elevation) of ST-segment of ECG in 2 or more leads lasting for 3 consecutive beats, occurring during at least one of the 3 mental stress tasks. | Week 6 |
| Percentage of Participants With Overall Mental Stress-induced Myocardial Ischemia (MSIMI) | MSIMI is defined by the following: compared to rest, 1) any development of new abnormal wall motion; 2) reduction of LVEF 8% and/or; 3) deviation (depression or elevation) of ST-segment of ECG in 2 or more leads lasting for 3 consecutive beats, occurring during at least one of the 3 mental stress tasks. | week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Mental Stress Induced Change of Systolic Blood Pressure | Blood pressure will be measured the last 3 minutes of the 20 minute calibration period (resting), every minute during the 3 minutes mental stress testing, the last 3 minutes of the 6 minute rest periods between mental stress testing, and every minute during and after the physical stress testing with an automatic oscillometric blood pressure monitor (Quinton Electronics). Mental Stress Induced Change of Systolic Blood Pressure will be calculated by taking the mean of the mental stress systolic blood pressure measurements minus the resting Systolic blood pressure. End point values adjusted for baseline values age and sex. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wei Jiang, M.D. | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22172432 | Background | Jiang W, Velazquez EJ, Samad Z, Kuchibhatla M, Martsberger C, Rogers J, Williams R, Kuhn C, Ortel TL, Becker RC, Pristera N, Krishnan R, O'Connor CM. Responses of mental stress-induced myocardial ischemia to escitalopram treatment: background, design, and method for the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment trial. Am Heart J. 2012 Jan;163(1):20-6. doi: 10.1016/j.ahj.2011.09.018. Epub 2011 Nov 14. | |
| 25323254 | Derived |
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25527 underwent initial screening. 22833 excluded due to reasons including no CHD, atrial fibrillation/arrhythmia, psychiatric disorder, and LVEF less than 30%. 2294 did not provide consent. 65 excluded due to medical conditions. 203 excluded due to no MSIMI or inability to undergo mental stress testing. 5 more declined to undergo randomization.
We screened all patients with Coronary Heart Disease (CHD) who visited Duke cardiology clinics. Patients 21 years or older were eligible to participate if they had CHD, as documented by angiographic findings of coronary artery stenosis of 70% or greater, history of MI, or history of cardiac revascularization.
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| ID | Title | Description |
|---|---|---|
| FG000 | Escitalopram | Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. |
| FG001 | Placebo | Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Escitalopram | Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With an Absence of Mental Stress-induced Myocardial Ischemia (MSIMI) During the 3 Mental Stressors | MSIMI is defined by the following: compared to rest, 1) any development of new abnormal wall motion; 2) reduction of LVEF 8% and/or; 3) deviation (depression or elevation) of ST-segment of ECG in 2 or more leads lasting for 3 consecutive beats, occurring during at least one of the 3 mental stress tasks. | Intent-to-treat (ITT) | Posted | Number | 95% Confidence Interval | percentage of participants | Week 6 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Escitalopram | Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Confusion, Hallucination | Nervous system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| fatigue | General disorders |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wei Jiang, MD | Duke University Medical Center | 919-668-0762 | jiang001@mc.duke.edu |
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| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 |
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|
| Placebo | Drug | Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. |
|
| Baseline, week 6 |
| Mental Stress Induced Change of Diastolic Blood Pressure | Blood pressure will be measured the last 3 minutes of the 20 minute calibration period (resting), every minute during the 3 minutes mental stress testing, the last 3 minutes of the 6 minute rest periods between mental stress testing, and every minute during and after the physical stress testing with an automatic oscillometric blood pressure monitor (Quinton Electronics). Mental Stress Induced Change of Diastolic Blood Pressure will be calculated by taking the mean of the mental stress Diastolic blood pressure measurements minus the resting Diastolic blood pressure. End point values adjusted for baseline values age and sex. | Baseline, week 6 |
| Percentage of Participants With Adverse Events | Baseline to week 6 |
| Beck Depression Inventory | The Beck Depression Inventory II (BDI-II) is a 21 question, self-administered measure of depressive symptoms. Score range, 0 to 63 (higher score=greater severity of depressive symptoms). End point values adjusted for baseline values age and sex. | 6 week |
| Mental Stress Induced Change in Heart Rate | A standard 12-lead Electrocardiograph (ECG) will be recorded at 1-minute intervals during the last 3 minutes of each rest period, the 3 minutes of the mental stress testing, and during exercise testing. Heart rate will be determined from the ECGs. Mental Stress Induced Change in heart rate will be calculated by taking the mean of the mental stress heart rate measurements minus the resting heart rate measurements. End point values adjusted for baseline values age and sex. | baseline, 6 weeks |
| 5HTT, Serotonin Transporter Protein | End point values adjusted for baseline values age and sex. | week 6 |
| Platelet Serotonin Binding Affinity Kd_100 | End point values adjusted for baseline values age and sex. | 6 weeks |
| Perceived Stress Scale | Score range, 10 to 50 (higher score = greater levels of perceived stress). End point values adjusted for baseline values age and sex. | 6 weeks |
| Cook-Medley Hostility (Ho) Scale | Score ranges: hostility, 0 to 27 (higher score=greater levels of hostility)/ End point values adjusted for baseline values age and sex. | 6 weeks |
| Cook-Medley Hostility (Ho) Hostile Affect Sub-scale | hostile affect, 0 to 5 (higher score=greater levels of hostile affect). End point values adjusted for baseline values age and sex. | 6 weeks |
| Spielberger State-Trait Anxiety Inventory Scales (STAI) | STAI measures anxiety. The questionnaire asks the patients how they feel and allows them to respond on a frequency scale that ranges from 1(not at all) to 4(almost always/very much so). Scores range from 20-80 and the higher the score the greater the anxiety level. This applies to both the Trait and State scales. End point values adjusted for baseline values age and sex. | 6 weeks |
| Exercise Stressed-induced Myocardial Ischemia (ESIMI) | End point values adjusted for baseline values age and sex. | 6 week |
| Samad Z, Boyle S, Ersboll M, Vora AN, Zhang Y, Becker RC, Williams R, Kuhn C, Ortel TL, Rogers JG, O'Connor CM, Velazquez EJ, Jiang W; REMIT Investigators. Sex differences in platelet reactivity and cardiovascular and psychological response to mental stress in patients with stable ischemic heart disease: insights from the REMIT study. J Am Coll Cardiol. 2014 Oct 21;64(16):1669-78. doi: 10.1016/j.jacc.2014.04.087. |
| 24631512 | Derived | Ersboll M, Al Enezi F, Samad Z, Sedberry B, Boyle SH, O'Connor C, Jiang W, Velazquez EJ; REMIT Investigators. Impaired resting myocardial annular velocities are independently associated with mental stress-induced ischemia in coronary heart disease. JACC Cardiovasc Imaging. 2014 Apr;7(4):351-61. doi: 10.1016/j.jcmg.2013.10.014. Epub 2014 Mar 13. |
| 24163385 | Derived | Boyle SH, Samad Z, Becker RC, Williams R, Kuhn C, Ortel TL, Kuchibhatla M, Prybol K, Rogers J, O'Connor C, Velazquez EJ, Jiang W. Depressive symptoms and mental stress-induced myocardial ischemia in patients with coronary heart disease. Psychosom Med. 2013 Nov-Dec;75(9):822-31. doi: 10.1097/PSY.0b013e3182a893ae. Epub 2013 Oct 25. |
| 23695483 | Derived | Jiang W, Velazquez EJ, Kuchibhatla M, Samad Z, Boyle SH, Kuhn C, Becker RC, Ortel TL, Williams RB, Rogers JG, O'Connor C. Effect of escitalopram on mental stress-induced myocardial ischemia: results of the REMIT trial. JAMA. 2013 May 22;309(20):2139-49. doi: 10.1001/jama.2013.5566. |
| 23410543 | Derived | Jiang W, Samad Z, Boyle S, Becker RC, Williams R, Kuhn C, Ortel TL, Rogers J, Kuchibhatla M, O'Connor C, Velazquez EJ. Prevalence and clinical characteristics of mental stress-induced myocardial ischemia in patients with coronary heart disease. J Am Coll Cardiol. 2013 Feb 19;61(7):714-22. doi: 10.1016/j.jacc.2012.11.037. |
| Withdrawal by Subject |
|
| Physician Decision |
|
| Did not receive medication (declined) |
|
Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| History of Depression | Number | participants |
|
| Placebo |
Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. |
|
|
| Secondary | Mental Stress Induced Change of Systolic Blood Pressure | Blood pressure will be measured the last 3 minutes of the 20 minute calibration period (resting), every minute during the 3 minutes mental stress testing, the last 3 minutes of the 6 minute rest periods between mental stress testing, and every minute during and after the physical stress testing with an automatic oscillometric blood pressure monitor (Quinton Electronics). Mental Stress Induced Change of Systolic Blood Pressure will be calculated by taking the mean of the mental stress systolic blood pressure measurements minus the resting Systolic blood pressure. End point values adjusted for baseline values age and sex. | ITT, 9 subjects excluded from analysis due to missing data. | Posted | Mean | 95% Confidence Interval | mm Hg | Baseline, week 6 |
|
|
|
| Secondary | Mental Stress Induced Change of Diastolic Blood Pressure | Blood pressure will be measured the last 3 minutes of the 20 minute calibration period (resting), every minute during the 3 minutes mental stress testing, the last 3 minutes of the 6 minute rest periods between mental stress testing, and every minute during and after the physical stress testing with an automatic oscillometric blood pressure monitor (Quinton Electronics). Mental Stress Induced Change of Diastolic Blood Pressure will be calculated by taking the mean of the mental stress Diastolic blood pressure measurements minus the resting Diastolic blood pressure. End point values adjusted for baseline values age and sex. | ITT, 9 subjects excluded from the analysis due to missing data. | Posted | Mean | 95% Confidence Interval | mm Hg | Baseline, week 6 |
|
|
|
| Secondary | Percentage of Participants With Adverse Events | Posted | Number | percentage of participants | Baseline to week 6 |
|
|
|
| Secondary | Beck Depression Inventory | The Beck Depression Inventory II (BDI-II) is a 21 question, self-administered measure of depressive symptoms. Score range, 0 to 63 (higher score=greater severity of depressive symptoms). End point values adjusted for baseline values age and sex. | ITT | Posted | Mean | 95% Confidence Interval | units on a scale | 6 week |
|
|
|
| Secondary | Mental Stress Induced Change in Heart Rate | A standard 12-lead Electrocardiograph (ECG) will be recorded at 1-minute intervals during the last 3 minutes of each rest period, the 3 minutes of the mental stress testing, and during exercise testing. Heart rate will be determined from the ECGs. Mental Stress Induced Change in heart rate will be calculated by taking the mean of the mental stress heart rate measurements minus the resting heart rate measurements. End point values adjusted for baseline values age and sex. | ITT, 10 subjects excluded from analysis due to missing data. | Posted | Mean | 95% Confidence Interval | beats/minute | baseline, 6 weeks |
|
|
|
| Secondary | 5HTT, Serotonin Transporter Protein | End point values adjusted for baseline values age and sex. | ITT, 29 subjects excluded from analysis due to missing data. | Posted | Mean | 95% Confidence Interval | fmol/mg | week 6 |
|
|
|
| Secondary | Platelet Serotonin Binding Affinity Kd_100 | End point values adjusted for baseline values age and sex. | ITT, 27 subjects were excluded from analysis due to missing data. | Posted | Mean | 95% Confidence Interval | nM | 6 weeks |
|
|
|
| Secondary | Perceived Stress Scale | Score range, 10 to 50 (higher score = greater levels of perceived stress). End point values adjusted for baseline values age and sex. | ITT | Posted | Mean | 95% Confidence Interval | units on a scale | 6 weeks |
|
|
|
| Secondary | Cook-Medley Hostility (Ho) Scale | Score ranges: hostility, 0 to 27 (higher score=greater levels of hostility)/ End point values adjusted for baseline values age and sex. | ITT, 1 subject excluded from analysis due to missing data. | Posted | Mean | 95% Confidence Interval | units on a scale | 6 weeks |
|
|
|
| Secondary | Cook-Medley Hostility (Ho) Hostile Affect Sub-scale | hostile affect, 0 to 5 (higher score=greater levels of hostile affect). End point values adjusted for baseline values age and sex. | ITT, 1 subject excluded from analysis due to missing data. | Posted | Mean | 95% Confidence Interval | units on a scale | 6 weeks |
|
|
|
| Secondary | Spielberger State-Trait Anxiety Inventory Scales (STAI) | STAI measures anxiety. The questionnaire asks the patients how they feel and allows them to respond on a frequency scale that ranges from 1(not at all) to 4(almost always/very much so). Scores range from 20-80 and the higher the score the greater the anxiety level. This applies to both the Trait and State scales. End point values adjusted for baseline values age and sex. | ITT | Posted | Mean | 95% Confidence Interval | units on a scale | 6 weeks |
|
|
|
| Secondary | Exercise Stressed-induced Myocardial Ischemia (ESIMI) | End point values adjusted for baseline values age and sex. | ITT, 7 subject excluded from analysis due to missing data. | Posted | Number | 95% Confidence Interval | percentage of change | 6 week |
|
|
|
| Primary | Percentage of Participants With Overall Mental Stress-induced Myocardial Ischemia (MSIMI) | MSIMI is defined by the following: compared to rest, 1) any development of new abnormal wall motion; 2) reduction of LVEF 8% and/or; 3) deviation (depression or elevation) of ST-segment of ECG in 2 or more leads lasting for 3 consecutive beats, occurring during at least one of the 3 mental stress tasks. | Subjects who completed. | Posted | Number | percentage of participants | week 6 |
|
|
|
| 3 |
| 64 |
| 46 |
| 64 |
| EG001 | Placebo | Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed. | 1 | 63 | 28 | 63 |
| Death | Cardiac disorders |
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| unstable angina | Cardiac disorders |
|
| burning sensation | Skin and subcutaneous tissue disorders |
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| CNS symptom | Nervous system disorders |
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| constipation | Gastrointestinal disorders |
|
| cramping in legs | Musculoskeletal and connective tissue disorders |
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| irregular heartbeat | Cardiac disorders |
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| sexual dysfunction | Reproductive system and breast disorders |
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| sinusitis | Infections and infestations |
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| Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |