eIMPACT Trial: Modernized Collaborative Care to Reduce the Excess CVD Risk of Older Depressed Patients
Study Details
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 |
|---|---|---|
|
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
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:
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:
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:
|
| 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 Names:
|
Outcome Measures
Primary Outcome Measures
- Brachial Artery Flow-Mediated Dilation (FMD) at 12 Months [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
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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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)
More Information
Publications
None provided.- 1411802537
- R01HL122245
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | eIMPACT | Usual Care |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 107 | 109 |
| COMPLETED | 99 | 100 |
| NOT COMPLETED | 8 | 9 |
Baseline Characteristics
| Arm/Group Title | eIMPACT | Usual Care | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 107 | 109 | 216 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.5
(6.0)
|
58.9
(5.4)
|
58.7
(5.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
83
77.6%
|
86
78.9%
|
169
78.2%
|
| Male |
24
22.4%
|
23
21.1%
|
47
21.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
5
4.7%
|
5
4.6%
|
10
4.6%
|
| Not Hispanic or Latino |
102
95.3%
|
104
95.4%
|
206
95.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
1
0.9%
|
1
0.5%
|
| Asian |
1
0.9%
|
0
0%
|
1
0.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
56
52.3%
|
51
46.8%
|
107
49.5%
|
| White |
45
42.1%
|
52
47.7%
|
97
44.9%
|
| More than one race |
4
3.7%
|
4
3.7%
|
8
3.7%
|
| Unknown or Not Reported |
1
0.9%
|
1
0.9%
|
2
0.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
107
100%
|
109
100%
|
216
100%
|
| Brachial Artery Flow-Mediated Dilation (% change in brachial diameter) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [% change in brachial diameter] |
2.59
(2.10)
|
2.84
(2.41)
|
2.71
(2.26)
|
Outcome Measures
| Title | Brachial Artery Flow-Mediated Dilation (FMD) at 12 Months |
|---|---|
| Description | 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. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 195 (98 intervention, 97 usual care) of the 199 participants who attended post-treatment had complete pre- and post-treatment brachial FMD data (3 had unscorable images, 1 did not undergo the post-treatment FMD). Because multiple imputation was employed, all 216 randomized participants were included in this analysis. |
| Arm/Group Title | eIMPACT | Usual Care |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 107 | 109 |
| Mean (Standard Deviation) [% change in brachial diameter] |
2.30
(1.92)
|
2.36
(2.20)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eIMPACT, Usual Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.83 |
| Comments | Because multiple imputation was employed, all 216 randomized participants were included in this analysis. | |
| Method | t-test, 2 sided | |
| Comments | ||
Adverse Events
| Time Frame | For each participant, adverse event monitoring occurred from each participant's randomization date until 9/1/20 (the date of the last EHR for all randomized participants). Thus, the adverse event monitoring period varied across participants but averaged 3.5 years. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Potential adverse events are identified by conducting EHR searches every 6 months and by reviewing self-report adverse event questionnaires from mid-treatment, post-treatment, and the annual follow-up calls. We investigate, rate, and write up all events plausibly related to depression, depression treatment, suicidal ideation, or any study procedures. We adjudicate all deaths. For all other captured events, we provide counts and will investigate further if there is evidence of group imbalance. | |||
| Arm/Group Title | eIMPACT | Usual Care | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| eIMPACT | Usual Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/107 (4.7%) | 8/109 (7.3%) | ||
Serious Adverse Events |
||||
| eIMPACT | Usual Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/107 (4.7%) | 4/109 (3.7%) | ||
| Endocrine disorders | ||||
| Diabetic ketoacidosis | 0/107 (0%) | 0 | 1/109 (0.9%) | 1 |
| Psychiatric disorders | ||||
| Hospitalization for depression/suicidal ideation | 2/107 (1.9%) | 2 | 1/109 (0.9%) | 1 |
| Emergency department visit for depression/suicidal ideation | 2/107 (1.9%) | 3 | 1/109 (0.9%) | 1 |
| Suspected drug overdose | 1/107 (0.9%) | 1 | 1/109 (0.9%) | 1 |
| Study procedures, including depression treatment | 0/107 (0%) | 0/109 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| eIMPACT | Usual Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/107 (2.8%) | 1/109 (0.9%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea following study-initiated suicidal ideation | 1/107 (0.9%) | 1 | 0/109 (0%) | 0 |
| Psychiatric disorders | ||||
| Passive suicidal ideation | 1/107 (0.9%) | 1 | 1/109 (0.9%) | 1 |
| Vascular disorders | ||||
| Petechiae on hand/wrist due to blood pressure cuff inflation during brachial FMD assessment | 1/107 (0.9%) | 1 | 0/109 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jesse C. Stewart, PhD., Principal Investigator |
|---|---|
| Organization | Indiana University-Purdue University Indianapolis (IUPUI) |
| Phone | 317-274-6761 |
| jstew@iupui.edu |
- 1411802537
- R01HL122245