Program ACTIVE II: Behavioral Depression Treatment for Type 2 Diabetes

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:

1. 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.

2. 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:

3. 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.

4. 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.

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