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

Phase 2

Completed

• Conditions: Depression; Depressive Symptoms; Heart Diseases; Coronary Artery Disease; Stroke; Major Depressive Disorder; Dysthymic Disorder; Cardiovascular Diseases
• Interventions: Behavioral: Beating the Blues (BtB); Other: Usual Care; Behavioral: Problem Solving Treatment in Primary Care (PST-PC); Drug: Antidepressant Medications

• Registration Number: NCT02458690
• Lead Sponsor: Indiana University

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-05-28
• Study First Submitted QC: 2015-05-29
• Study First Posted: 2015-06-01
• Study Start: 2015-07
• Primary Completion: 2019-08
• Results First Submitted: 2020-08-31
• Results First Submitted QC: 2020-09-21
• Results First Posted: 2020-10-14
• Study Completion: 2021-03
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-03
• Last Update Posted: 2023-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 216

Inclusion Criteria

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
eIMPACT	Beating the Blues (BtB)	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.
eIMPACT	Problem Solving Treatment in Primary Care (PST-PC)	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.
eIMPACT	Antidepressant Medications	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.
Usual Care	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.

Primary Outcome Measures

Name	Time	Method
Brachial Artery Flow-Mediated Dilation (FMD) at 12 Months	12 months	Brachial FMD was measured per consensus guidelines using a GE LOGIQe high-resolution ultrasound with a 15-MHz vascular transducer. After a 10-minute supine rest period, a BP cuff was placed on the forearm and inflated to 250 mmHg for five minutes. Brachial diameter was measured at pre-inflation and 60- and 90-seconds post-deflation using AccessPoint 2011 software (version 8.2). FMD was computed the maximum % increase in brachial diameter at 60- or 90-seconds post-deflation.

Secondary Outcome Measures

Name	Time	Method
Depressive Symptoms at 12 Months	12 months	Participants completed the reliable and valid Hopkins Symptom Checklist-20 (SCL-20) to assess depressive symptoms. Total scores (mean of items responses, range: 0-4) were computed, with higher scores indicating greater depressive symptoms.
High-Sensitivity C-Reactive Protein (hsCRP) at 12 Months	12 months	Fasting blood samples obtained by research nurses were collected in EDTA tubes and centrifuged within 20 min. Plasma aliquots were frozen at -80 °C until the time of assay at the Indiana University Center for Diabetes and Metabolic Diseases Translation Core. Using enzyme-linked immunosorbent assay kits according to the manufacturer's instructions, we measured levels of hsCRP.
Platelet Factor 4 (PF4) at 12 Months	12 months	Fasting blood samples obtained by research nurses were collected in EDTA tubes and centrifuged within 20 min. Plasma aliquots were frozen at -80 °C until the time of assay at the Indiana University Center for Diabetes and Metabolic Diseases Translation Core. Using enzyme-linked immunosorbent assay kits according to the manufacturer's instructions, we measured levels of PF4.
High-Frequency Heart Rate Variability (HF HRV) at 12 Months	12 months	HF HRV estimates were derived by spectral analysis (bandwidth: 0.15-0.40 Hz) from 1-minute epochs of electrocardiographic data obtained during the last 5 min of the 10-minute supine rest period using MindWare Technologies HRV analysis software (version 3.1.2). Mean HF HRV was computed as the average of the five estimates. To control for respiration rate, participants completed a paced-breathing computer task set to 12 breaths/minute.
β-thromboglobulin at 12 Months	12 months	Fasting blood samples obtained by research nurses were collected in EDTA tubes and centrifuged within 20 min. Plasma aliquots were frozen at -80 °C until the time of assay at the Indiana University Center for Diabetes and Metabolic Diseases Translation Core. Using enzyme-linked immunosorbent assay kits according to the manufacturer's instructions, we measured levels of β-thromboglobulin.
Interleukin-6 (IL-6) at 12 Months	12 months	Fasting blood samples obtained by research nurses were collected in EDTA tubes and centrifuged within 20 min. Plasma aliquots were frozen at -80 °C until the time of assay at the Indiana University Center for Diabetes and Metabolic Diseases Translation Core. Using enzyme-linked immunosorbent assay kits according to the manufacturer's instructions, we measured levels of IL-6.

Trial Locations

Locations (1)

IUPUI Department of Psychology; 🇺🇸 Indianapolis, Indiana, United States