Clinical trial NCT00574847: Responses of Myocardial Ischemia to Escitalopram Treatment
Official title: Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Ischemia
Keywords: ischemic heart disease
mental stress-induced myocardial ischemia
escitalopram
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-12-17
Enrollment: 127
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With an Absence of Mental Stress-induced Myocardial Ischemia (MSIMI) During the 3 Mental Stressors
timeFrame: Week 6
measure: Percentage of Participants With Overall Mental Stress-induced Myocardial Ischemia (MSIMI)
timeFrame: week 6
Secondary outcomes:
measure: Mental Stress Induced Change of Systolic Blood Pressure
timeFrame: Baseline, week 6
measure: Mental Stress Induced Change of Diastolic Blood Pressure
timeFrame: Baseline, week 6
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline to week 6
measure: Beck Depression Inventory
timeFrame: 6 week
measure: Mental Stress Induced Change in Heart Rate
timeFrame: baseline, 6 weeks
measure: 5HTT, Serotonin Transporter Protein
timeFrame: week 6
measure: Platelet Serotonin Binding Affinity Kd_100
timeFrame: 6 weeks
measure: Perceived Stress Scale
timeFrame: 6 weeks
measure: Cook-Medley Hostility (Ho) Scale
timeFrame: 6 weeks
measure: Cook-Medley Hostility (Ho) Hostile Affect Sub-scale
timeFrame: 6 weeks
measure: Spielberger State-Trait Anxiety Inventory Scales (STAI)
timeFrame: 6 weeks
measure: Exercise Stressed-induced Myocardial Ischemia (ESIMI)
timeFrame: 6 week
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Wei Jiang, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.