Program ACTIVE II: Behavioral Depression Treatment for Type 2 Diabetes

Study Overview
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Brief Summary
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Program ACTIVE II is a depression treatment study sponsored by the National Institutes of Health, Indiana University, Ohio University and West Virginia University. The purpose of this study is to test the effectiveness of two forms of treatment for depression for adults with type 2 diabetes: talk therapy (counseling) and exercise. Both of these forms of treatment have been proven to be effective in helping people with depression alone. In this study, the investigators will test to see if both of these approaches may be more effective in helping people live depression-free compared to talk therapy, exercise or usual care alone.

Detailed Description
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Program ACTIVE II is a study funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R18DK092765) designed to test the combined effectiveness of two behavioral treatments for depression in people with type 2 diabetes: individual counseling (cognitive behavioral therapy; CBT) and exercise. While each of these treatment approaches has been tested individually in people with depression, no study has tested the combination of these approaches for people with major depression and type 2 diabetes. These approaches have the potential to work synergistically as a win-win strategy to improve both T2DM and depression outcomes while extending the reach of formal health care treatment strategies for diabetes. Two primary study aims will be addressed by Program ACTIVE II: 1) to compare changes in glycemic control across intervention groups to UC at POST and 6- and 12-month follow-up assessments; and 2) to compare changes in MDD outcomes across intervention groups (i.e. CBT, EXER, CBT+EXER) to usual care (UC) following intervention (POST) and 6- and 12-month follow-up assessments. The primary hypotheses are: Diabetes Outcomes. Based on the investigators' pilot data, mean glycemic control (as measured by HbA1c) is expected to improve .4% in participants in the EXER and CBT+EXER treatment conditions at POST compared to baseline [de Groot et al 2009]. Participants assigned to the CBT+EXER treatment are expected to show the greatest improvement in HbA1c followed by those in the EXER group in comparison to the CBT group. No improvement is expected among those assigned to the UC condition. Depression. Participants in the CBT, EXER and CBT+EXER conditions will show clinically significant improvements in BDI and diagnosis of MDD at POST and 6- and 12-month assessments with the greatest improvements expected among those in CBT+EXER condition. Based on pilot data, a) 66% reduction in the number of people who meet DSM-IV criteria for MDD is expected at POST compared to baseline; b) 86-90% percent of cases with MDD remission at POST are expected to remain remitted at the 6-month follow-up; c) severity of depression, as measured by the BDI-II, will significantly decrease from baseline to POST and baseline to follow-up assessments, after co-varying the effect of gender, number of T2DM complications, and exposure to treatment. It is anticipated that participants in the CBT+EXER condition will show the longest remission rates of depression followed by those in EXER and CBT. The secondary hypotheses are: Changes in CVD risk factors in the intervention groups compared to UC over time. Physical activity capacity, as measured by the 6-minute walk test (6MWT), will demonstrate the greatest improvements in the CBT+EXER arm, closely followed by the EXER arm at follow-up assessment compared to baseline. Participants in the CBT and UC arms are not expected to show significant improvements. LDL-C is expected to improve at POST in the EXER and CBT+EXER conditions consistent with pilot data. Cost Effectiveness Analyses. The predicted incidence of complications, particularly coronary heart disease (CHD), will be lower among those who receive CBT+EXER condition compared to the CBT, EXER and UC conditions. Further, the costs of this intensive intervention will be offset by a decrease in complication incidence.

Official Title
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Program ACTIVE II: Behavioral Depression Treatment for Type 2 Diabetes

Conditions
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Type2 Diabetes, Depression

Intervention / Treatment
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* Behavioral: Program ACTIVE Exercise
* Behavioral: Program ACTIVE CBT
* Behavioral: Program ACTIVE
* Behavioral: Usual Care - No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: able to walk without the use of a cane or walker diagnosis of type 2 diabetes for at least one year duration or longer major depression lasting two weeks or longer Exclusion Criteria: history of diabetic ketoacidosis (DKA) history of continuous insulin therapy since diabetes diagnosis stage 2 hypertension as defined by JNC VII recent cardiac events (e.g., unstable angina, diagnosed angina, PTCA, any cardiac intervention for CAD or tachydysrhythmias in the past six months) laser surgery for proliferative retinopathy in the past six months history of stroke, lower limb amputation, asensory peripheral neuropathy, aortic stenosis or other sever valvular heart disease, atrial fibrillation, severe COPD (e.g., basal oxygen), class III or IV heart failure active suicidal ideation or history of suicide attempt history of bipolar disorder history of psychotic disorder current substance abuse or dependence disorder individuals who report the use of a current antidepressant medication for five weeks or less were excluded or deferred for later screening after the 6 week period individual who were receiving psychotherapy from a mental health provider for depression were excluded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study subjects were randomly assigned to one of the four groups: talk therapy, exercise, talk therapy + exercise, or usual care. Separate randomization lists were generated by the study statistician for use by each of the three study sites.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Talk therapy (CBT)<br>Participants randomized the talk therapy arm received 10 weeks of CBT or talk therapy. The goal of CBT was to provide individuals with skills and concepts that they may use to: 1) manage and reduce depressive symptoms; 2) prevent the onset and severity of future depressive episodes; and 3) generalize these skills to diabetes management. CBT interventionists facilitated patient management of depressive symptoms by providing participants with: Education about depression and the cognitive-behavioral therapy model; A safe relationship for participants to explore their symptom patterns and try to new tools to address them; Coaching as participants fully engage emotional and behavioral strategies. | Behavioral: Program ACTIVE CBT<br>* Please see the Talk Therapy arm description above.<br>|
| Experimental: Exercise (EXER)<br>Participants randomized to the exercise arm were enrolled in a 12-week physical activity intervention designed to increase aerobic physical activity. Participants were asked to complete 100 minutes of aerobic activity in Week 1, 125 minutes in Week 2, and 150 minutes per week of physical activity in Weeks 3-12. In addition, participants received 6 exercise training classes in which safe exercise practices were introduced and practiced, free access to a local exercise facility, use of a pedometer, completion of activity logs each week, and received an exercise workbook that addressed social and motivational aspects of physical activity. | Behavioral: Program ACTIVE Exercise<br>* Please see the Exercise arm description above.<br>|
| Experimental: Talk therapy + exercise (CBT+EXER)<br>Participants randomized to the combination therapy received both talk therapy and exercise as detailed above. | Behavioral: Program ACTIVE<br>* Please see the Talk Therapy + Exercise arm description above.<br>|
| Placebo Comparator: Usual care (UC)<br>Participants randomized to usual care received no study intervention. | Behavioral: Usual Care - No intervention<br>* Please see the Usual Care arm description above.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Based on our pilot data, mean glycemic control (as measured by HbA1c) is expected to improve .4% in participants in the EXER and CBT + EXER treatment conditions at POST compared to baseline (de Groot et al., 2009). Participants assigned to the CBT + EXER treatment are expected to show the greatest improvement in HbA1c followed by those in the EXER group in comparison to the CBT group. No improvement is expected among those assigned to the UC condition. | following completion of intervention ( 3 months), 6-months following completion of intervention, and 12-months following completion of intervention | 
| Change in depression status - Beck Depression Inventory | Participants in the CBT, EXER and CBT + EXER conditions will show clinically significant improvements in BDI at POST, 6- and 12-month assessments with the greatest improvements expected among those in CBT + EXER condition. Based on pilot data, severity of depression, as measured by the BDI-II, will significantly decrease from baseline to POST and baseline to follow-up assessments, after co-varying the effect of gender, number of T2DM complications, and exposure to treatment. | following completion of intervention ( 3 months), 6-months following completion of intervention, and 12-months following completion of intervention | 
| Change in depression status - Diagnosis of Major Depressive Disorder | Participants in the CBT, EXER and CBT + EXER conditions will show clinically significant improvements in diagnosis of MDD at POST, 6- and 12-month assessments with the greatest improvements expected among those in CBT + EXER condition. Based on pilot data, a) a 66% reduction in the number of people who meet DSM-IV criteria for MDD is expected at POST compared to baseline; b) 86-90% percent of cases with MDD remission at POST are expected to remain remitted at the 6-month follow-up, after co-varying the effect of gender, number of T2DM complications, and exposure to treatment. It is anticipated that participants in the CBT + EXER condition will show the longest remission rates of depression followed by those in EXER and CBT. | following completion of intervention ( 3 months), 6-months following completion of intervention, and 12-months following completion of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cardiovascular (CVD) risk factors | Changes in CVD risk factors in the intervention groups compared to UC over time. Physical activity capacity, as measured by the 6-minute walk test (6MWT), will demonstrate the greatest improvements in the CBT + EXER arm, closely followed by the EXER arm at follow-up assessment compared to baseline. Participants in the CBT and UC arms are not expected to show significant improvements. LDL-C is expected to improve at POST in the EXER and CBT + EXER conditions, consistent with pilot data. | following completion of intervention ( 3 months), 6-months following completion of intervention, and 12-months following completion of intervention | 
| Cost effectiveness analyses | The cost of predicted incidence of complications, particularly coronary heart disease (CHD), will be lower among those who receive the CBT + EXER condition compared to the CBT, EXER and UC conditions. Further, the costs of this intensive intervention will be offset by a decrease in complication incidence. | following completion of intervention ( 3 months), 6-months following completion of intervention, and 12-months following completion of intervention |