Clinical trial NCT03263351: Depression & Insulin Sensitivity in Adolescents
Official title: Depression and Insulin Sensitivity in Adolescents
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type2 Diabetes
Type 2 Diabetes Mellitus
Insulin Sensitivity
Insulin Resistance
Depression
Adolescent Obesity
Lead sponsor: Colorado State University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Center for Advancing Translational Sciences (NCATS)
name: Children's Hospital Colorado
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-08-28
Enrollment: 200
Sex: FEMALE
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized controlled behavioral trial with two conditions - cognitive-behavioral therapy group or health education group - run in parallel.
Primary purpose: PREVENTION

Brief summary: There has been a rise in type 2 diabetes (T2D) rates in adolescents, disproportionately in girls from disadvantaged racial/ethnic groups. This group of girls also is at heightened risk for depression, and depression and T2D are linked. Depressive symptoms are a risk factor for worsening of insulin sensitivity, one if the major precursors to T2D. In preliminary studies, the investigators found that a brief cognitive-behavioral therapy group decreased depressive symptoms and prevented worsening of insulin sensitivity in adolescent girls at-risk for T2D with moderate depressive symptoms. The aims of this study are: 1) to assess the efficacy of a cognitive-behavioral therapy depression group vs. a health education control group for improving insulin sensitivity and preserving insulin secretion in racially/ethnically diverse adolescent girls at-risk for T2D with moderate depressive symptoms over a 1-year follow-up; 2) to evaluate changes in eating, physical activity, and sleep as explanatory and 3) to test changes in cortisol factors as explanatory.

Detailed description: There has been rapid escalation of type 2 diabetes (T2D) rates in adolescents. Early-onset T2D (\<20y) typically shows a more aggressive course than adult-onset T2D and disproportionately affects girls from disadvantaged, racial/ethnic groups. This group of girls also is at heightened risk for depression, and depression and T2D are linked. Depressive symptoms often manifest in adolescence and are a prospective risk factor for worsening of insulin sensitivity, the major physiological precursor-in combination with deterioration of pancreatic β-cell capacity to secrete insulin-in the path to T2D. The effects of depression on poor insulin sensitivity remain even after accounting for adiposity. In theory, depressive symptoms may worsen insulin sensitivity through stress-induced behaviors (e.g., disinhibited eating, physical inactivity, sleep disturbance) and stress-induced physiological causal mechanisms (e.g., hypercortisolism). The central theme of this study is that intervening to reduce depressive symptoms in adolescents at-risk for T2D may offer an innovative, targeted approach to ameliorate insulin resistance and to, consequently, preserve β-cell function and lessen T2D risk. In preliminary data, the investigators found initial evidence that a 6-week cognitive-behavioral group decreased depressive symptoms and prevented worsening of insulin sensitivity 1 year later in overweight and obese girls with moderate depressive symptoms and a family history of T2D, in comparison to a 6-week health education control group. Directly extending these findings, the primary aims of this study are: 1) to assess the efficacy of a 6-week cognitive-behavioral depression group vs. a 6-week health education control group for improving insulin sensitivity and preserving β-cell function in racially/ethnically diverse adolescent girls at-risk for T2D with moderate depressive symptoms over a 1-year follow-up; 2) to evaluate changes in eating, physical activity, and sleep as behavioral explanatory mediators underlying the relationship between decreases in depressive symptoms and improvements in insulin sensitivity and β-cell function over 1 year and 3) to test changes in cortisol awakening response, diurnal cortisol rhythm, and total daily cortisol output as physiological mechanisms explaining the relationship between decreases in depressive symptoms and improvements in insulin sensitivity and β-cell function over 1 year.

Eligibility criteria: Inclusion Criteria:

* Female
* Age 12-17 years
* Body mass index (BMI) ≥85th percentile for age \& sex
* Center for Epidemiologic Studies-Depression Scale (CES-D) \>20
* English speaking
* ≥1 first- or second-degree family member with type 2 diabetes (T2D), prediabetes, or gestational diabetes
* Good general health

Exclusion Criteria:

* Pregnancy or breastfeeding
* Type 2 diabetes as indicated by fasting glucose≥126 mg/dL or 2-hour glucose\>200 mg/dL or Hba1c\>=6.5
* Medication affecting mood, weight, cortisol, or insulin sensitivity, including insulin sensitizers (e.g., metformin), anti-depressants, and stimulants
* Major psychiatric disorder that, in the opinion of the investigators, would impede study compliance and necessitate more intensive treatment, including major depressive disorder, bipolar disorder, posttraumatic stress disorder, panic disorder, obsessive-compulsive disorder, schizophrenia, conduct disorder, alcohol and substance abuse, and anorexia/bulimia nervosa
* Psychotherapy or structured weight loss program
* Active suicidal ideation or suicidal behavior

Primary outcomes:
measure: Depressive symptoms
timeFrame: 1-year
measure: Insulin sensitivity
timeFrame: 1-year
measure: Insulin secretion
timeFrame: 1-year
Secondary outcomes:
measure: Disinhibited eating
timeFrame: 1-year
measure: Physical activity
timeFrame: 1-year
measure: Physical inactivity
timeFrame: 1-year
measure: Sleep
timeFrame: 1-year
measure: Cortisol diurnal rhythm
timeFrame: 1-year
measure: Daily cortisol output
timeFrame: 1-year
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
References:
citation: Andrews SA, Colvin HJ. Verification of Intoximeter 3000 breath alcohol concentration by magnesium perchlorate tube method in long-term field program. J Anal Toxicol. 1989 Mar-Apr;13(2):113-6. doi: 10.1093/jat/13.2.113.
citation: Shomaker LB, Kelly NR, Radin RM, Cassidy OL, Shank LM, Brady SM, Demidowich AP, Olsen CH, Chen KY, Stice E, Tanofsky-Kraff M, Yanovski JA. Prevention of insulin resistance in adolescents at risk for type 2 diabetes with depressive symptoms: 1-year follow-up of a randomized trial. Depress Anxiety. 2017 Oct;34(10):866-876. doi: 10.1002/da.22617. Epub 2017 Mar 31.