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

Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02458690
• Other study ID #: 1411802537
• Secondary ID: R01HL122245
• Status: Completed
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: March 2021

Study information

• Verified date: October 2023
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: March 2021
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Symptoms
• Dysthymic Disorder
• Heart Diseases
• Major Depressive Disorder
• Stroke

Intervention

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.
• 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.

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:
• 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.

Locations

Country	Name	City	State
United States	IUPUI Department of Psychology	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brachial Artery Flow-Mediated Dilation (FMD) at 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.	12 months
Secondary	Depressive Symptoms at 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.	12 months
Secondary	High-Frequency Heart Rate Variability (HF HRV) at 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.	12 months
Secondary	Interleukin-6 (IL-6) at 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.	12 months
Secondary	High-Sensitivity C-Reactive Protein (hsCRP) at 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.	12 months
Secondary	ß-thromboglobulin at 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 ß-thromboglobulin.	12 months
Secondary	Platelet Factor 4 (PF4) at 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.	12 months