Responses of Myocardial Ischemia to Escitalopram Treatment

Overview

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.

Full Title of Study: “Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT Trial)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 2011

Detailed Description

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.

Interventions

  • Drug: 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.
  • Drug: 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.

Arms, Groups and Cohorts

  • Experimental: Escitalopram
    • Escitalopram treatment
  • Placebo Comparator: Placebo
    • Placebo

Clinical Trial Outcome Measures

Primary Measures

  • Percentage of Participants With an Absence of Mental Stress-induced Myocardial Ischemia (MSIMI) During the 3 Mental Stressors
    • Time Frame: Week 6
    • 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.
  • Percentage of Participants With Overall Mental Stress-induced Myocardial Ischemia (MSIMI)
    • Time Frame: week 6
    • 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.

Secondary Measures

  • Mental Stress Induced Change of Systolic Blood Pressure
    • Time Frame: Baseline, week 6
    • 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.
  • Mental Stress Induced Change of Diastolic Blood Pressure
    • Time Frame: Baseline, week 6
    • 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.
  • Percentage of Participants With Adverse Events
    • Time Frame: Baseline to week 6
  • Beck Depression Inventory
    • Time Frame: 6 week
    • 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.
  • Mental Stress Induced Change in Heart Rate
    • Time Frame: baseline, 6 weeks
    • 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.
  • 5HTT, Serotonin Transporter Protein
    • Time Frame: week 6
    • End point values adjusted for baseline values age and sex.
  • Platelet Serotonin Binding Affinity Kd_100
    • Time Frame: 6 weeks
    • End point values adjusted for baseline values age and sex.
  • Perceived Stress Scale
    • Time Frame: 6 weeks
    • Score range, 10 to 50 (higher score = greater levels of perceived stress). End point values adjusted for baseline values age and sex.
  • Cook-Medley Hostility (Ho) Scale
    • Time Frame: 6 weeks
    • Score ranges: hostility, 0 to 27 (higher score=greater levels of hostility)/ End point values adjusted for baseline values age and sex.
  • Cook-Medley Hostility (Ho) Hostile Affect Sub-scale
    • Time Frame: 6 weeks
    • hostile affect, 0 to 5 (higher score=greater levels of hostile affect). End point values adjusted for baseline values age and sex.
  • Spielberger State-Trait Anxiety Inventory Scales (STAI)
    • Time Frame: 6 weeks
    • 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.
  • Exercise Stressed-induced Myocardial Ischemia (ESIMI)
    • Time Frame: 6 week
    • End point values adjusted for baseline values age and sex.

Participating in This Clinical Trial

Inclusion Criteria

  • Age 21 or greater, less than 90 – Stable ischemic heart disease Exclusion Criteria:

  • Recent myocardial infarction, coronary artery bypass graft surgery, or other revascularization procedures (less than 3 months ago) – Left ventricular ejection fraction(LVEF) < 15% measured by echocardiography, radionuclide ventriculography (RNV), or cardiac catheterization – Life threatening arrhythmia or arrhythmia interrupting the interpretation of ischemia – Unable to withdraw from anti-anginal medications during ischemic assessment phase – Unable to perform exercise testing – Pregnancy – Current or previous history of bipolar disorder, cyclothymia, schizophrenia, schizoaffective or schizophreniform disorder, or other psychotic disorders – Active suicidal ideation – Current substance abuse or history of substance abuse in the previous 6 months – Significant cardiac, pulmonary, metabolic, renal, hepatic disease, or malignancy, interfering with patient's participation in this study – Seizure (history and/or present) with/without treatment – Currently taking antidepressants that cannot be discontinued

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Duke University
  • Collaborator
    • National Heart, Lung, and Blood Institute (NHLBI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Wei Jiang, M.D., Principal Investigator, Duke University

References

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.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.