eIMPACT-DM Pilot Trial: Depression Treatment to Reduce Diabetes Risk

• ClinicalTrials.gov Identifier: NCT04437485
• Recruitment Status: Recruiting
• First Posted: June 18, 2020
• Last Update Posted: January 20, 2022
• Sponsor: Indiana University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Jesse Stewart, Indiana University

Study Description

Brief Summary:

This pilot randomized controlled trial seeks: (1) to determine the preliminary efficacy of our modernized collaborative care intervention for depression in improving the diabetes risk markers of hemoglobin A1c and insulin resistance and (2) to explore whether somatic depressive symptoms - i.e., hyperphagia (increased appetite/weight) and/or hypersomnia (increased sleep) - moderate the effect of the eIMPACT-DM intervention on diabetes risk markers.

Condition or disease	Intervention/treatment	Phase
Depression; Major Depressive Disorder; Dysthymic Disorder; Depressive Symptoms; Type 2 Diabetes; PreDiabetes; Insulin Resistance	Behavioral: Good Days Ahead (GDA); Behavioral: Problem Solving Treatment in Primary Care (PST-PC); Drug: Antidepressant Medications; Other: Active Control	Phase 2

Detailed Description:

Diabetes affects 31 million (12%) U.S. adults, and another 82 million (34%) adults have prediabetes, a precursor to diabetes. The ramifications of diabetes are grave and include cardiovascular disease, disability, and death. While these statistics highlight the importance of diabetes prevention, current approaches have only partial effectiveness. This has created a clear need to identify new primary prevention targets and approaches for diabetes, and depression and depression treatment are strong candidates in this regard. Over 20 years of evidence indicates that depression is an independent, clinically important, robust, biobehaviorally plausible, and modifiable risk factor for diabetes. However, research has yet to determine whether depression treatment can prevent the development of diabetes in people with prediabetes. Given that depression is still receiving limited attention in settings where diabetes prevention occurs (e.g., primary care), there is a large cohort of patients with an underdetected or undertreated diabetes risk factor (depression). This status quo and the strong state of the depression-to-diabetes science create the need for a pilot randomized controlled trial to evaluate the utility of depression treatment as a new diabetes prevention strategy. Thus, we propose a pilot RCT of 64 primary care patients (50% minority) with a depressive disorder and prediabetes. Patients will be randomized to 6 months of eIMPACT-DM (intervention) or Active Control (comparator). eIMPACT-DM is our 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 diabetes risk reduction. Our preliminary data establish the feasibility and antidepressive efficacy of eIMPACT-DM. The Active Control consists of depression education, symptom monitoring, and primary care for depression. Our primary aim is to determine the preliminary efficacy of eIMPACT-DM in improving the diabetes risk markers of hemoglobin A1c (primary outcome) and insulin resistance (secondary outcome). Our exploratory aim is to explore whether somatic depressive symptoms - i.e., hyperphagia (increased appetite/weight) and/or hypersomnia (increased sleep) - moderate the effect of eIMPACT-DM on diabetes risk markers. A positive pilot trial would pave the way to an R01-level RCT by: (1) generating critical proof-of-concept data (eIMPACT-DM can improve A1c) to support the premise of the definitive trial; (2) providing preliminary effect sizes for eIMPACT-DM on diabetes risk markers to help justify future power analyses; (3) identifying a potentially important moderator of eIMPACT-DM efficacy that may need to be incorporated into the definitive trial. Ultimately, demonstrating that depression treatment reduces diabetes risk would identify a novel target (depression) for diabetes prevention efforts, and it would equip healthcare providers with a new practical, scalable, and disseminable intervention (eIMPACT-DM) to help lower diabetes risk for a large cohort of high-risk patients. These practice changes should translate into reduced diabetes morbidity, mortality, and costs.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: eIMPACT-DM Pilot Trial: Depression Treatment to Reduce the Excess Diabetes Risk of People With Depression and Prediabetes
• Actual Study Start Date: October 14, 2020
• Estimated Primary Completion Date: September 30, 2022
• Estimated Study Completion Date: January 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: eIMPACT-DM intervention; eIMPACT-DM is a 6-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 diabetes 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 Good Days Ahead, 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 (PCPs).	Behavioral: Good Days Ahead (GDA); GDA (Empower Interactive) is an empirically supported, HIPAA compliant, computerized CBT for depression appropriate for primary care patients and people with little computer experience. GDA uses an interactive, multimedia format to deliver 9 45-minute sessions, the structure and content of which mirror face-to-face CBT. General topics include identifying and modifying automatic thoughts, using behavioral activation and other behavioral methods, identifying and modifying schemas, using effective coping strategies, and employing other core CBT methods. GDA is empirically supported - it is acceptable to patients, achieves superior depression outcomes to waitlist comparators, and yields equivalent (noninferior) depression outcomes to standard face-to-face CBT. To minimize time/transportation barriers, GDA sessions occur at the PI's lab or a location with internet access selected by the patient (patient's, family member's, or friend's home).; Other Names: Cognitive-Behavioral Therapy (CBT); Internet Psychotherapy; Behavioral: Problem Solving Treatment in Primary Care (PST-PC); PST-PC is an established, manualized, empirically supported CBT developed for primary care. During the 6-10 30-minute sessions, patients are taught skills for solving problems contributing to depression. We will deliver PST-PC by phone, which has been found to be feasible and efficacious.; Other Names: Cognitive-Behavioral Therapy (CBT); Telephonic Psychotherapy; Drug: Antidepressant Medications; We first considered all FDA-approved antidepressants and excluded those with weight gain effects (tricyclics, paroxetine, mirtazapine) and those rarely used in primary care (MAOIs). Then, we used existing evidence to inform the structure. We made bupropion (an aminoketone) and fluoxetine (an SSRI) our first-line and second-line antidepressants, as meta-analyses indicate that their use is associated with weight loss. We made other SSRIs (escitalopram, sertraline) and SNRIs (desvenlafaxine, duloxetine, venlafaxine) our third-line antidepressants, given their negligible effects on weight. Our team will make recommendations to the patient's PCP, who will write prescriptions. Our team and the PCP will then collaboratively manage pharmacotherapy.; Other Names: Bupropion; Selective Serotonin Reuptake Inhibitors (SSRIs); Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Active Comparator: Active Control; Active Control (AC) consists of depression education (study staff), symptom monitoring (study staff), and primary care for depression (clinical staff).	Other: Active Control; (1) The graduate research assistant (RA) will have a 50-minute call with AC patients to review depression materials. The RA will provide a list of Eskenazi Health mental health services and will encourage patients to follow-up with their PCP. We will then send an electronic health record message to the PCP encouraging them to address their patient's depression, note that there are no care restrictions, and provide the same list of services. (2) The RA will call AC patients every 4 weeks to assess depressive symptoms and will notify clinical staff to encourage additional care when indicated. (3) AC patients will receive current primary care for depression. The Eskenazi Health primary care clinics utilize a team care approach, with PCPs supported by embedded behavioral health clinicians and affiliated psychiatrists.

Outcome Measures

Primary Outcome Measures :

1. Change in Hemoglobin A1c at 6 months [ Time Frame: Baseline and 6 months ]
   Fasting blood samples will be collected, and whole blood and plasma aliquots will be frozen. A1c will be measured by an immunoturbidimetric method on a Randox Daytona Clinical Analyzer.A1c is the primary outcome because: (1) it is the gold standard measure of glycemia and a common surrogate endpoint, (2) it strongly predicts future diabetes, (3) interventions decreasing A1c improve clinical diabetes endpoints, and (4) diabetes prevention interventions targeting glycemic control result in lower rates of progression from prediabetes to type 2 diabetes. Thus, A1c is well suited to evaluate if a new intervention approach holds promise.

Secondary Outcome Measures :

1. Change in Homeostatic Model of Assessment (HOMA) score at 6 months [ Time Frame: Baseline and 6 months ]
   Fasting blood samples will be collected, and whole blood and plasma aliquots will be frozen. HOMA scores will be derived from fasting glucose (glucose oxidase method on a Randox Daytona Clinical Analyzer) and insulin (two antibody immunoassay on a Roche cobas e411 Analyzer). HOMA score is an established index of insulin resistance that correlates highly with the more invasive euglycemic clamp and is appropriate for assessing change.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Current primary care patient in Eskenazi Health
• Age ≥18 years
• Depressive disorder at screening
• Prediabetes at screening

Exclusion Criteria:

• History of type 1 or type 2 diabetes
• Major inflammatory conditions: HIV/AIDS, chronic kidney disease, systemic inflammatory disease (e.g., rheumatoid arthritis, lupus, Crohn's disease, and ulcerative colitis), or active cancer/current cancer treatment
• Current pregnancy
• Severe cognitive impairment
• Acute risk of suicide
• History of bipolar disorder or psychosis or current use of an atypical antipsychotic medication:
• Participation in our prior eIMPACT Trial

Contacts and Locations

Contacts

Contact: Jesse C Stewart, PhD; 317-274-6761; jstew@iupui.edu

Locations

United States, Indiana

IUPUI Department of Psychology; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Jesse C Stewart, Ph.D. 317-274-6761 jstew@iupui.edu

Sponsors and Collaborators

Indiana University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

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

More Information

• Responsible Party: Jesse Stewart, Professor of Psychology, Indiana University
• ClinicalTrials.gov Identifier: NCT04437485
• Other Study ID Numbers: 1908716624; R21DK123582 ( U.S. NIH Grant/Contract )
• First Posted: June 18, 2020
• Last Update Posted: January 20, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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; Cognitive-Behavioral Therapy; Computer-Based Psychotherapy; Antidepressant Medications

Additional relevant MeSH terms:

Diabetes Mellitus; Insulin Resistance; Prediabetic State; Glucose Intolerance; Disease; Depression; Depressive Disorder; Depressive Disorder, Major; Dysthymic Disorder; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Behavioral Symptoms; Mood Disorders; Mental Disorders; Hyperinsulinism; Hyperglycemia; Norepinephrine; Bupropion; Antidepressive Agents; Serotonin; Serotonin Uptake Inhibitors; Antidepressive Agents, Second-Generation; Psychotropic Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents