Exercise and Pharmacotherapy for Anxiety in Cardiac Patients

NCT ID: NCT02516332

Last Updated: 2021-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2021-05-31

Brief Summary

Coronary heart disease (CHD) is the leading cause of death in the United States; more than 600,000 Americans suffer a fatal cardiac event each year. Traditional CHD risk factors such as high blood pressure, smoking, and elevated cholesterol do not fully account for the timing and occurrence of CHD events and individuals with elevated levels of anxiety appear to have a greater risk of cardiovascular events. The present study will examine the impact of aerobic exercise and Lexapro in the treatment of anxiety and cardiovascular biomarkers among individuals with CHD.

Detailed Description

Coronary heart disease (CHD) is the leading cause of death in the United States; more than 600,000 Americans suffer a fatal cardiac event each year. Traditional CHD risk factors such as high blood pressure, smoking, and elevated cholesterol do not fully account for the timing and occurrence of CHD events. The term "cardiovascular vulnerable patient" has been used to describe patients susceptible to acute coronary events based upon plaque, blood, or myocardial characteristics. Psychosocial factors also have been shown to be associated with increased adverse health outcomes and increased cardiovascular vulnerability. For example, clinical depression and elevated depressive symptoms are associated with increased morbidity and mortality, and as a result, the American Heart Association has recommended that clinicians should routinely assess depression in CHD patients. Although much research and clinical recommendations have focused on depression, the significance of anxiety has been largely ignored, despite the fact that anxiety disorders are as prevalent as depression in the general population and are associated with similar levels of disability.

Despite the prevalence and prognostic significance of anxiety in CHD populations, there have been few randomized clinical trials (RCTs) specifically targeting anxious CHD patients. Anxiolytic medications, including selective serotonin reuptake inhibitors (SSRIs), have been shown to be effective in treating anxiety. SSRIs have been evaluated for the treatment of clinical depression in cardiac patients, with equivocal results. Surprisingly, to our knowledge, there have been no RCTs examining the efficacy of medications for treating anxiety in CHD patients. Moreover, because many cardiac patients are reluctant to take additional medications and psychotropic medications may not be effective for everyone or may produce unwanted side effects, there continue to be a need to identify alternative approaches for treating anxiety in cardiac patients. The investigators believe that exercise may be one such approach.

The purpose of this study is to evaluate the following hypotheses in a population of CHD patients with elevated symptoms of anxiety. The present study will examine the impact of a 3-month intervention of either exercise, Lexapro, or placebo on anxiety symptoms and CHD biomarkers among individuals with cardiac disease and elevated anxiety. The investigators hypothesize that: (1) Both exercise training and medication will reduce anxiety symptoms to a greater extent than placebo; (2) Exercise training will improve CHD biomarkers of risk including autonomic regulation, vascular endothelial function, and inflammation more than either medication or placebo; and (3) Improvements in CHD biomarkers will be mediated by reductions in symptoms of anxiety. The investigators also will explore potential moderators of treatment (e.g., anxiety diagnoses, CHD severity) as well as the longer-term benefits of treatment by documenting medical events and health care costs over a follow-up period of up to 4 years.

Conditions

Anxiety; Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Supervised Aerobic Exercise

Patients will exercise three times per week, under medical supervision, at a level of 70-85% of their VO2peak as determined at the time of their baseline exercise stress test. Patients' exercise will consist of 10 minutes of gradual warm-up exercises followed by 35 minutes of continuous walking, biking, or jogging, and 5 minutes of cool down exercises for a total a 50 minutes per session. Patients will be instructed to monitor their radial pulses and will be checked at least three times per session to ensure that they are within their prescribed exercise training ranges.

Group Type: EXPERIMENTAL

Supervised Aerobic Exercise

Intervention Type: BEHAVIORAL

Lexapro

Treatment in the medication will be supervised by a study psychiatrist. Drug dispensing will be done by licensed pharmacists at the Duke Investigational Pharmacy Service. The investigators will use the SSRI escitalopram (Lexapro), which has received FDA approval for the treatment of anxiety, in 5 mg capsules. Medication will be dispensed as capsules of escitalopram in individually coded bottles. Medication adherence will be assessed using pill count at each study visit. Patients will visit face-to-face with a study psychiatrist at week 0 (baseline), week 1, week 2, week 4, week 8, and week 12 with phone encounters at weeks 3 and 6. The psychiatrist will make all medication adjustments based primarily upon Spielberger Anxiety Scores. Depending on symptoms, daily escitalopram doses will be titrated to 10 mg after week 2 and to 15 mg or placebo equivalent at week 3 if patients show no change or only minimal improvement.

Group Type: EXPERIMENTAL

Lexapro

Intervention Type: DRUG

Placebo

Treatment in the medication and placebo pill arms will be supervised by a study psychiatrist. Drug dispensing will be done by licensed pharmacists at the Duke Investigational Pharmacy Service, who have extensive experience in clinical trials. Medication will be taken once daily in the morning but can be switched to once daily in the evening if deemed necessary. Placebo medication administration will follow the same protocol as outlined for Lexapro.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Lexapro

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Supervised Aerobic Exercise

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Men and women with documented CHD (i.e., a prior MI, coronary revascularization procedure, or >70% stenosis in at least one coronary artery)
• Age > 39 years
• Patients also will have an anxiety symptom severity score of at least 8 on the Hospital Anxiety and Depression-Anxiety scale (HADS-A) or a DSM-5 diagnosis of an Anxiety Disorder, such as General Anxiety, Social Anxiety, or Panic Disorder.

The study team plans to actively recruit women and minorities, with at least 50% women and 25% minorities.

Exclusion Criteria

• An MI or coronary revascularization procedure (i.e., CABG or percutaneous coronary intervention) within the last 3 months
• Unstable angina
• Severe left ventricular dysfunction (ejection fraction <30%) or decompensated heart failure
• Unrevascularized left main coronary artery stenosis >50%
• Complete Pacemaker dependence
• Resting BP >200/120 mm Hg
• Conditions that would preclude randomization to either the drug (e.g., prolonged QT interval, known allergy to or intolerance of escitalopram) or exercise (e.g., musculoskeletal problems or abnormal cardiac response to exercise)
• Patients with a primary psychiatric diagnosis other than Anxiety Disorder will be excluded, including patients with PTSD, OCD, or any of the following DSM-5 diagnoses:

1. Dementia, delirium;

2. Schizophrenia, Schizoaffective, or other psychotic disorder;

3. Psychotic features including any delusions or hallucinations; or

4. Current alcohol or other substance abuse disorder.

• Similarly, patients who pose an acute suicide or homicide risk or who, during the course of the study, would likely require treatment with additional psychopharmacologic agents will not be enrolled.
• Patients will also be excluded if they are taking other medications that would preclude assignment to either drug or exercise conditions (e.g., clonidine, dicumarol, anticonvulsants, and MAO inhibitors) or are taking herbal supplements with purported mood effects (e.g., St. John's Wort, valerian, ginkgo).
• Patients already engaged in regular exercise (at least 30 minutes >1x/week) will not be enrolled.
• Finally, pregnant women will be excluded from participation.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

Blumenthal JA, Smith PJ, Jiang W, Hinderliter A, Watkins LL, Hoffman BM, Kraus WE, Liao L, Davidson J, Sherwood A. Effect of Exercise, Escitalopram, or Placebo on Anxiety in Patients With Coronary Heart Disease: The Understanding the Benefits of Exercise and Escitalopram in Anxious Patients With Coronary Heart Disease (UNWIND) Randomized Clinical Trial. JAMA Psychiatry. 2021 Nov 1;78(11):1270-1278. doi: 10.1001/jamapsychiatry.2021.2236.

Reference Type: DERIVED

PMID: 34406354 (View on PubMed)

Blumenthal JA, Feger BJ, Smith PJ, Watkins LL, Jiang W, Davidson J, Hoffman BM, Ashworth M, Mabe SK, Babyak MA, Kraus WE, Hinderliter A, Sherwood A. Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial. Am Heart J. 2016 Jun;176:53-62. doi: 10.1016/j.ahj.2016.03.003. Epub 2016 Mar 12.

Reference Type: DERIVED

PMID: 27264220 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00064329

Identifier Type: -

Identifier Source: org_study_id