eIMPACT Trial: Modernized Collaborative Care to Reduce the Excess CVD Risk of Older Depressed Patients

• ClinicalTrials.gov Identifier: NCT02458690
• Recruitment Status: Completed
• First Posted: June 1, 2015
• Results First Posted: October 14, 2020
• Last Update Posted: September 27, 2021
• Sponsor: Indiana University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Jesse Stewart, Indiana University

Study Description

Brief Summary:

The objective of this randomized controlled trial is to evaluate whether the investigators modernized IMPACT intervention for depression (eIMPACT), delivered before the onset of cardiovascular disease (CVD), reduces the risk of future CVD. Participants will be primary care patients who are depressed but do not have a history of CVD. Half of the participants will receive standard depression treatment in primary care (usual care), and the other half will receive one year of eIMPACT, a collaborative stepped care program including antidepressants and computerized and telephonic cognitive-behavioral therapy. To evaluate change in CVD risk, the investigators will measure artery function using ultrasound before and after the 1-year treatment period. It is hypothesized that patients who receive the eIMPACT intervention will have greater improvements in artery function than patients who receive usual care.

Condition or disease	Intervention/treatment	Phase
Depression; Major Depressive Disorder; Dysthymic Disorder; Depressive Symptoms; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Stroke	Behavioral: Beating the Blues (BtB); Behavioral: Problem Solving Treatment in Primary Care (PST-PC); Drug: Antidepressant Medications; Other: Usual Care	Phase 2

Detailed Description:

Cardiovascular disease (CVD) is the number one killer of American men and women, and its economic burden is substantial and on the rise. Adults with depression are at elevated risk of CVD events and poor CVD prognosis. Unfortunately, past trials of depression treatments have not observed the anticipated cardiovascular benefits. A novel explanation for these null results is that the interventions in these trials, which all involved patients with preexisting CVD, were delivered too late in the natural history of CVD. To begin to evaluate our hypothesis that treating depression before clinical CVD onset could reduce CVD risk, the investigators are conducting a phase II randomized controlled trial of 216 primary care patients aged ≥ 50 years with a depressive disorder and CVD risk factors but no clinical CVD. Patients will be randomized to one year of eIMPACT, our modernized IMPACT intervention, or usual primary care for depression. eIMPACT is a collaborative stepped care intervention involving a multidisciplinary team delivering evidenced-based depression treatments consistent with patient preference. The investigator shave modernized our intervention by incorporating computerized cognitive-behavioral therapy and delivering other treatment components via telephone. Our central hypothesis is that eIMPACT will improve endothelial dysfunction, which is considered a barometer of CVD risk, in depressed adults by decreasing depressive symptoms, autonomic dysfunction, systemic inflammation, and platelet activation. The investigators will test our central hypothesis by carrying out these specific aims: (1) to determine whether eIMPACT reduces the excess CVD risk of depressed patients (primary outcome: endothelial dysfunction; exploratory outcome: incident CVD events) and (2) to examine candidate mechanisms underlying the effect of eIMPACT on CVD risk (secondary outcomes: depressive symptoms, autonomic dysfunction, systemic inflammation, and platelet activation). A positive trial would generate the mechanistic rationale, efficacy evidence, and effect size estimates needed to justify and design a multisite, event-driven, phase III trial to confirm eIMPACT's efficacy in reducing CVD risk. Demonstrating that depression treatment reduces CVD risk, the primary expected outcome of this line of research, would have a substantial positive impact. It would identify a novel target (depression) for CVD prevention efforts, and it would equip providers with a new disseminable and scalable tool (eIMPACT) to simultaneously treat depression and manage the CVD risk of a large cohort of high-risk patients. Collectively, these changes to clinical practice should translate into reduced CVD morbidity, mortality, and costs.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: eIMPACT Trial: Modernized Collaborative Care to Reduce the Excess CVD Risk of Older Depressed Patients
• Actual Study Start Date: July 2015
• Actual Primary Completion Date: August 2019
• Actual Study Completion Date: March 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: eIMPACT; eIMPACT is a 12-month, modernized, collaborative, stepped care intervention consisting of (1) computerized and telephonic cognitive-behavioral therapy for depression and (2) select antidepressant medications included in an algorithm optimized for cardiovascular disease risk reduction. It is a collaborative care intervention in which a multidisciplinary team delivers established depression treatments consistent with patient preference. It uses a stepped, flexible, treat-to-target approach that modernizes the IMPACT intervention by harnessing technology to minimize staff and space requirements. Interventions are Beating the Blues, Problem Solving Treatment in Primary Care, and select FDA-approved antidepressants. The treatment team consists of a depression clinical specialist, a supervising MD with expertise in primary care and IMPACT, and the patients' primary care providers.	Behavioral: Beating the Blues (BtB); BTB is a widely used, empirically supported, stand-alone CBT program for depression designed for primary care patients and appropriate for adults with little computer experience and a 5th-6th grade reading level. BtB utilizes an interactive, multimedia format to deliver eight 50-minute, weekly therapy sessions. Although sessions are tailored to each patient's problems, general topics include challenging dysfunctional thoughts, activity scheduling, problem solving, graded exposure, task breakdown, sleep management, and relapse prevention. Patients are also assigned tailored homeworks that are customized to their needs and reviewed at the start of each session.; Other Names: Cognitive-Behavioral Therapy (CBT); Computer-Based Psychotherapy; Behavioral: Problem Solving Treatment in Primary Care (PST-PC); PST-PC is a manualized, empirically supported CBT developed for use by healthcare professionals in primary care. The focus of the 6-10 30-minute sessions is teaching patients approaches for solving current problems contributing to depression. We are delivering PST-PC via telephone.; Other Names: Cognitive-Behavioral Therapy (CBT); Telephonic Psychotherapy; Drug: Antidepressant Medications; The IMPACT treatment manual provides guidelines for using antidepressants, such as selecting a medication, titrating, switching to another medication, managing side effects, and avoiding drug interactions. To optimize eIMPACT for CVD risk reduction, we have restricted the IMPACT list of antidepressants to SSRIs (sertraline, escitalopram, paroxetine, fluoxetine, citalopram), duloxetine, bupropion, and mirtazapine. These medications are FDA approved for the treatment of depression and are the safest from a cardiovascular perspective.; Other Names: Selective Serotonin Reuptake Inhibitors (SSRIs); Serotonin-Norepinephrine Reuptake Inhibitor (SNRI); Norepinephrine-Dopamine Reuptake Inhibitor (NDRI); Tetracyclic Antidepressant (TeCA)
Active Comparator: Usual Care; Patients and their primary care providers are informed of the depressive disorder diagnosis, and follow-up is encouraged. There are no restrictions on the care received. The Eskenazi Health primary care clinics utilize a team care approach, with PCPs supported by embedded behavioral health clinicians and affiliated psychiatrists.	Other: Usual Care; Patients randomized to usual primary care for depression are informed of their depression diagnosis, encouraged to follow-up with their Eskenazi Health primary care provider, and provided a list of local mental health services. The patient's primary care provider will receive a letter indicating that their patient has a depressive disorder and was randomized to usual care. This letter also provides a list of local mental health services. Like those in the intervention group, usual care patients continue to have access to services that are part of usual care in the targeted systems. There are no restrictions on the care received. The Eskenazi Health primary care clinics utilize a team care approach, with PCPs supported by embedded behavioral health clinicians and affiliated psychiatrists.; Other Name: Treatment As Usual (TAU)

Outcome Measures

Primary Outcome Measures :

1. Brachial Artery Flow-Mediated Dilation (FMD) at 12 Months [ Time Frame: 12 months ]
   Patients undergo ultrasound assessment of brachial FMD in accordance with established guidelines. After a 10-minute supine rest, high-resolution baseline images of the brachial artery will be obtained from 3 consecutive cardiac cycles. Next, the forearm cuff will be inflated to 250 mmHg for 5 minutes and then will be rapidly deflated. At 60 and 90 seconds post-deflation, images from 3 consecutive cardiac cycles will be acquired. FMD values will be computed as the % change (positive values=increase; negative values=decrease) in brachial diameter at either 60 or 90 seconds after cuff deflation.

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Primary care patients
• Age ≥ 50 years
• Current depressive disorder
• Elevated cardiovascular disease risk

Exclusion Criteria:

• History of clinical cardiovascular disease
• Presence of the following chronic disorders: HIV/AIDS, chronic kidney disease, systemic inflammatory disease, or past-year cancer
• History of bipolar disorder or psychosis
• Continuous (e.g., daily) treatment for a systemic inflammatory condition (e.g., rheumatoid arthritis, lupus, Crohn's disease, and ulcerative colitis) in the past 3 months. Nonsteroidal anti-inflammatory drug (NSAID) use is allowed, given its high prevalence in the target population.
• Current use of anticoagulants (Aspirin and cholesterol and blood pressure medications are allowed)
• Acute risk of suicide
• Severe cognitive impairment
• Current pregnancy
• Ongoing depression treatment with a psychiatrist outside of the Eskenazi Health/Midtown system (ongoing depression treatment with a Eskenazi Health/Midtown psychiatrist is allowed, as we will be able to collaborate and coordinate depression care)

Contacts and Locations

Locations

United States, Indiana

IUPUI Department of Psychology

Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Jesse C Stewart, Ph.D.; Indiana University-Purdue University Indianapolis (IUPUI)

  Study Documents (Full-Text)

Documents provided by Jesse Stewart, Indiana University:

Study Protocol and Statistical Analysis Plan  [PDF] July 13, 2018

Informed Consent Form  [PDF] July 13, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shell AL, Gonzenbach V, Sawhney M, Crawford CA, Stewart JC. Associations between affective factors and high-frequency heart rate variability in primary care patients with depression. J Psychosom Res. 2022 Oct;161:110992. doi: 10.1016/j.jpsychores.2022.110992. Epub 2022 Jul 22.

• Responsible Party: Jesse Stewart, Professor of Psychology, Indiana University
• ClinicalTrials.gov Identifier: NCT02458690
• Other Study ID Numbers: 1411802537; R01HL122245 ( U.S. NIH Grant/Contract )
• First Posted: June 1, 2015
• Results First Posted: October 14, 2020
• Last Update Posted: September 27, 2021
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Jesse Stewart, Indiana University:

Primary Care; Older Adults; Computerized and Telephonic Psychotherapy; Cognitive-Behavioral Therapy; Antidepressant Medications

Additional relevant MeSH terms:

Cardiovascular Diseases; Coronary Artery Disease; Heart Diseases; Disease; Depression; Depressive Disorder; Depressive Disorder, Major; Dysthymic Disorder; Pathologic Processes; Behavioral Symptoms; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Mood Disorders; Mental Disorders; Dopamine; Norepinephrine; Antidepressive Agents; Serotonin; Selective Serotonin Reuptake Inhibitors; Dopamine Uptake Inhibitors; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Sympathomimetics