Exercise and Pharmacotherapy for Anxiety in Cardiac Patients

NCT02516332 | Completed Results DMC

• 1 other identifier: Pro00064329
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

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.

Conditions

Anxiety; Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• Change in Hospital Anxiety and Depression Scale (HADS), Anxiety

  The Hospital Anxiety and Depression Scale, Anxiety, is a 7-item subscale with scores ranging from 0-21, with higher scores indicating more anxiety.

  Baseline, 3 months

Secondary Outcomes (6)

• Change in Heart Rate Variability, SDNN (Msec)

  Baseline, 3 months

• Change in Baroreflex Sensitivity, ms/mm Hg

  Baseline, 3 months

• Change in Vascular Endothelial Function, Percentage of Dilation

  Baseline, 3 months

• Change in Inflammation (C-Reactive Protein, ug/ml)

  Baseline, 3 months

• Change in Urinary Catecholamines (Epinephrine and Norepinephrine, Unit-weighted Z-score)

  Baseline, 3 months

Other Outcomes (1)

• Change in Hospital Anxiety and Depression Scale, Total Score

  9 months, 15 months

Study Arms (3)

Supervised Aerobic Exercise

EXPERIMENTAL

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.

Behavioral: Supervised Aerobic Exercise

Lexapro

EXPERIMENTAL

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.

Drug: Lexapro

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Lexapro DRUG

Lexapro

Placebo DRUG

Placebo

Supervised Aerobic Exercise BEHAVIORAL

Supervised Aerobic Exercise

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Dementia, delirium;
• Schizophrenia, Schizoaffective, or other psychotic disorder;
• Psychotic features including any delusions or hallucinations; or
• 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.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• 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.

  PMID: 34406354 DERIVED

• 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.

  PMID: 27264220 DERIVED

MeSH Terms

Conditions

Anxiety Disorders; Cardiovascular Diseases

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Patrick Smith, Ph.D.
• Organization: Duke University

patrick.j.smith@duke.edu

919-681-3006

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 5, 2015
• Study Start: December 1, 2015
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2021
• Last Updated: June 11, 2021
• Results First Posted: June 11, 2021

Record last verified: 2021-06

Locations

US (1)