Cognitive-Behavioral Therapy and Exercise Training in Adolescents At-Risk for Type 2 Diabetes

Study Overview
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Brief Summary
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The investigators are doing this study to learn more about how to prevent type 2 diabetes in teenage girls. The purpose of this study is to find out if taking part in a cognitive-behavioral therapy group, exercise training group, or a combination of cognitive-behavioral therapy and exercise training groups, decreases stress, improves mood, increases physical activity and physical fitness, and decreases insulin resistance among teenagers at risk for diabetes.

Detailed Description
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There has been rapid escalation in adolescent-onset type 2 diabetes (T2D), particularly in females from historically disadvantaged racial/ethnic groups. Prevention is critical because adolescent-onset T2D often shows a more aggressive disease course than adult-onset, and effective treatment options remain elusive. Standard-of-care for T2D prevention includes exercise training to ameliorate insulin resistance, a key physiological precursor to T2D. Despite short-term benefits, exercise training shows insufficient effectiveness in adolescents at-risk for T2D. Depression may be explanatory in a considerable subset of teenagers. Adolescence is notable for increases in depression and decreases in physical activity, especially in females with obesity. Youths' depression symptoms contribute to worsening insulin resistance over time, independent of BMI (kg/m2), likely through stress-mediated pathways such as reduced physical activity and fitness. Also, adolescent depression is associated with decreased physical activity and cardiorespiratory fitness, even after accounting for adiposity, and depression predicts greater non-adherence to exercise training. The central theme of this proposal is that an intervention sequence of delivering cognitive-behavioral therapy (CBT) first, followed by intervening with exercise training second, will offer a targeted, efficacious strategy for improving insulin resistance and consequently, lowering T2D risk in adolescent females at-risk for T2D with depression symptoms. In a prior National Institute of Health (NIH) /National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K99/R00 randomized controlled trial (RCT), the investigators found that 6-week group CBT decreased depression at 6-week follow-up in adolescent females at-risk for T2D with moderately elevated depression, compared to a 6-week didactic health education control group. Adolescents with elevated depression who were randomized to CBT had lower fasting and 2-hour insulin at 1-year vs. controls. Our preliminary data suggest that CBT's focus on enhancing frequency/enjoyment of physical activity to combat depressed mood partially explained why decreasing depression lowered T2D risk. It is not known if CBT is just as efficacious as standard-of-care exercise training, or whether CBT followed by exercise training results in a maximally potent alleviation of T2D risk in adolescent females at-risk for T2D with depression symptoms. To address these gaps and directly build on our prior work, the investigators propose a four-arm RCT to: (1) Compare the efficacy of four 6-week-->6-week sequences for improving insulin resistance in N=300 adolescent females at-risk for T2D with elevated depression symptoms: (i) CBT-->exercise, (ii) exercise-->CBT, (iii) CBT only (CBT-->continue CBT), and (iv) exercise only (exercise-->continue exercise); (2) Evaluate physical activity/fitness as mediators underlying the depression-insulin resistance association; and (3) Evaluate underlying mechanisms by which decreasing depression increases physical activity and improves fitness and insulin resistance using a mixed-methods process evaluation. Findings will support our long-term goal to identify feasible, cost-effective intervention strategies with high potential for effective dissemination to adolescents at-risk for T2D with elevated depression symptoms.

Official Title
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Cognitive-Behavioral Therapy and Exercise Training in Adolescents At-Risk for Type 2 Diabetes

Conditions
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Insulin Resistance, Depression, Depressive Disorder, Mood Disorders, Mental Disorder in Adolescence, Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Disease

Intervention / Treatment
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* Behavioral: Cognitive-Behavioral Therapy followed by Exercise Training
* Behavioral: Exercise Training followed by Cognitive-Behavioral Therapy
* Behavioral: Cognitive-Behavioral Therapy Only
* Behavioral: Exercise Training Only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Age 12-17 years Body Mass Index (BMI)>= 85 for age and sex Type 2 Diabetes (T2D) first-or second-degree relative Center for Epidemiologic Studies Depression Scale (CES-D) total score >=21 Exclusion Criteria: T2D/ Type 1 Diabetes (T1D) or any major medical condition (e.g. cardiovascular, renal) that would prohibit the ability to participate in exercise training Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) conduct disorder, substance abuse/ dependence, obsessive compulsive disorder, panic attacks, post-traumatic stress disorder, anorexia/bulimia, & schizophrenia Regular medication use affecting mood, insulin, or weight, including stimulants, anti-depressants, anti-psychotics, insulin sensitizers, weight loss medications & chronic steroids Regular psychotherapy, structured weight loss treatment, or bariatric surgery Pregnancy, nursing

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive-Behavioral Therapy followed by Exercise Training<br>6-week cognitive-behavioral therapy intervention of 6 weekly 1-hour group sessions followed by a 6-week exercise training intervention of 6 weekly 1-hour group sessions | Behavioral: Cognitive-Behavioral Therapy followed by Exercise Training<br>* 6-week group CBT (cognitive-behavioral therapy; 1 hour/week for 6 weeks) followed by 6-week group exercise training (1 hour/week for 6 weeks). Home practice is assigned throughout the 12-week intervention period.<br>* Other names: CBT->Exercise Training;|
| Active Comparator: Exercise Training followed by Cognitive-Behavioral Therapy<br>6-week exercise training intervention of 6 weekly 1-hour group sessions followed by a 6-week cognitive-behavioral therapy intervention of 6 weekly 1-hour group sessions | Behavioral: Exercise Training followed by Cognitive-Behavioral Therapy<br>* 6-week group exercise training (1 hour/week for 6 weeks) followed by 6-week group CBT (1 hour/week for 6 weeks). Home practice is assigned throughout the 12-week intervention period.<br>* Other names: Exercise Training -> CBT;|
| Active Comparator: Exercise Training Only<br>6-week exercise training intervention of 6 weekly 1-hour group sessions followed by an additional 6-week exercise training intervention of 6 weekly 1-hour group sessions | Behavioral: Cognitive-Behavioral Therapy Only<br>* 6-week group CBT (1 hour/week for 6 weeks), with continuation of group CBT for a second 6-week period (1 hour/week for 6 weeks). Home practice is assigned throughout the 12-week intervention period.<br>* Other names: CBT Only;|
| Active Comparator: Cognitive-Behavioral Therapy Only<br>6-week cognitive-behavioral therapy intervention of 6 weekly 1-hour group sessions followed by an additional 6-week cognitive-behavioral therapy intervention of 6 weekly 1-hour group sessions | Behavioral: Exercise Training Only<br>* 6-week group exercise training (1 hour/week for 6 weeks), with continuation of group exercise for a second 6-week period (1 hour/week for 6 weeks). Home practice is assigned throughout the 12-week intervention period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Resistance | Homeostatic model assessment of insulin resistance (HOMA-IR) estimated from fasting insulin and glucose as part of oral glucose tolerance testing | 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Insulin sensitivity index (ISI) derived from fasting and two-hour insulin and glucose as part of oral glucose tolerance testing | 1-year | 
| Cardiorespiratory fitness | Maximum volume of oxygen (VO2 peak) during cycle ergometry testing using a graded protocol to exertion | 1-year | 
| Rate Perceived Exertion | Adolescent report on the Borg Scale during cycle ergometry testing | 1-year | 
| Exercise enjoyment | Adolescent report on the Physical Activity Enjoyment Scale (PACES), total score | 1-year | 
| Exercise self-efficacy | Adolescent report on the Exercise Self-Confidence Survey, total score | 1-year | 
| Exercise perceived capability | Adolescent report on the Physical Activity, Patient-Reported outcome Measurement Information System (PROMIS) Short Form | 1-year | 
| Depression symptoms | Adolescent report on the 20-item Center for Epidemiologic Studies-Depression Scale (CES-D), total score | 1-year | 
| Depressive disorder | Schedule for Affective Disorders and Schizophrenia for School-Aged Youth - Computerized Version (KSADS-COMP) interview with adolescent | 1-year | 
| Eating behavior | Habitual macronutrient/food group intake reported 3 days (2 weekdays, 1 weekend) on the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) | 1-year | 
| Sleep quality | Adolescent report on the Pittsburgh Sleep Quality Index, total score | 1-year | 
| Sleep disturbance | Adolescent report on the Insomnia Severity Index, total score | 1-year | 
| BMI | Derived from height in triplicate by stadiometer and fasting weight by calibrated scale; raw (kg/m2) and z-score/percentile based upon Centers for Disease Control and Prevention (CDC) growth charts | 1-year | 
| Adiposity | Fat/fat-free mass measured via air displacement plethysmography in a fasted state (BodPod) | 1-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescent Type 2 Diabetes Prevention, Exercise Training