Resilience Promotion in Teens With Type 1 Diabetes: Preventing Negative Outcomes

1. Scope of Problem: Adolescents with type 1 diabetes (T1D) must balance a complex daily
treatment regimen while also facing the emotional, social and academic demands of this
developmental period. Not surprisingly, adolescents are at increased risk for anxiety
and depressive symptoms, poor coping and problem-solving skills, poor regimen
adherence, and negative diabetes-specific health outcomes. The mental and physical
health risks of T1D add to its already staggering economic burden; the annual cost of
diabetes in the United States for direct medical care exceeds $116 billion and
individuals with diabetes have twice the healthcare costs of their peers without
diabetes.

A handful of psychological interventions targeting adolescents' poor behavioral and
emotional functioning demonstrate beneficial effects on disease management and
outcomes. However, no prevention programs exist that equip adolescents with behavioral
skills and cognitive strategies shown to reduce both the risk of poor psychological
functioning and the risk of negative health outcomes over time. Although none of the
effective prevention programs developed for healthy youth have been adapted for
adolescents with T1D, the Penn Resilience Program (PRP) is a viable candidate because
it is a well-established prevention program shown to promote resilience and prevent
depression. The current study will test a diabetes-specific adaptation of PRP for
adolescents with T1D and fill a significant gap in the scientific literature.

This study's significance lies not only in its focus on preventing depression, a
prevalent, critical factor influencing diabetes-specific health outcomes, but also in
its emphasis on ultimately preventing suboptimal glycemic control, a common, expensive,
and dangerous problem in pediatric diabetes. Individuals with both depression and
diabetes incur 4.5 times the health care costs as those with diabetes alone. The focus
of the intervention on resilience promotion is innovative because of its potential to
fundamentally change risk for depression and set adolescents on a trajectory toward
improved adherence and health outcomes. Moreover, documenting the mechanisms of change
that impact critical psychosocial and health outcomes in youth with T1D via a
longitudinal, randomized, controlled design facilitates generalizability to other
chronically ill populations given similar management demands on the individual and
family, and associations with depression.

2. Summary of Procedures: Investigators will employ a randomized, controlled design and
compare PRP T1D to a diabetes education intervention, (EI; developed by two CDE's,
specifically focused on adolescent learning and adolescent needs) on resilience
characteristics, depressive symptoms, adherence behaviors, and glycemic outcomes.
Investigators will recruit 280 adolescents with T1D across two cities (Chicago and
Cincinnati), measuring outcomes at baseline, post-intervention, and at five
surveillance visits spanning an additional 24 months. All adolescents will participate
in 9 sessions, lasting approximately 90 minutes each session. Assessments occur at
baseline (0 months), post-intervention (4.5 months), and during the surveillance period
(8, 12, 16, and 28 months).

PRP T1D will be led by master's level graduate students enrolled in clinical psychology
PhD programs. EI will be led by CDE nurses. This EI group is preferable to either
untreated control or wait-list control groups as it allows for the experimental control
of attention, peer group sessions, and dose on treatment outcomes. Both program leaders
will receive over 20 hours of training in the program they are leading.

Data Collection and Measures. Measures assess two primary outcomes (depressive symptoms
and glycemic control) and two mechanisms of change (resilience and adherence).
Assessments occur at baseline, post-intervention (4.5 months), and 4 surveillance
visits (8, 12, 16, and 28 months). To keep participant burden at a manageable level and
to increase retention rate, all eligible families will be invited to complete the
questionnaires on a secured web-site that they can access while with the research study
staff, or while at home, work, in a public library or while in clinic. Investigators
will use the SNAP Survey Software system, which allows for electronic completion of
surveys with data directly transferred to data management software in a HIPAA-protected
framework. The SNAP software eliminates the need for manual data entry, reducing the
risk of missing data as well as reducing the risk of violating the confidentiality of
the data.

Hemoglobin A1c will be collected via a small sample of blood and sent to a central
laboratory. The Diabetes Diagnostic Laboratory at the University of Missouri
(http://www.diabetes.missouri.edu/)will be used. This laboratory served as the
reference laboratory for the DCCT and NHANES III and IV studies. They have extensive
experience serving as a central laboratory for A1c values.

Continuous glucose monitoring (CGM; iPro sensor and transmitter by Medtronic) will
assess glycemic variability. The certified diabetes educator (CDE) or study physician
will assist each participant with the insertion and calibration of the device. For this
study, adolescents will be blinded to the CGM values for safety reasons; we do not want
participants adjusting insulin levels or dietary intake based on sensor readings.
Adolescents will wear the sensor and transmitter for 3 days. After use, the
sensor/transmitter will be collected by the research team via a pre-paid mailing
container. Once the transmitter is returned, the data are downloaded to study
computers, typically with 290 values per day. Investigators then calculate three
indicators of glycemic variability: SD of the mean of the sensor values, mean amplitude
of glycemic excursions (MAGE), and percentage of time spent within glucose ranges. The
amount of time spent "within target" (values between 70 and 180), "below target"
(values below 70), and "above target" (values above 180) will be calculated. All three
indicators are well-established metrics of glycemic variability.

Enhancing Treatment Fidelity. Per the NIH Behavior Change Consortium,27 a randomized,
controlled design is the most effective mechanism for finding treatment effects.
Further, it is vital to insure all interventions are delivered as proposed and
participants receive the same treatment dose within and across the intervention
conditions. To achieve this, Investigators will make uniform reminder calls, use
treatment manuals, and interventionists will meet every other week with the study PIs
for group supervision to discuss relevant topics, problem areas, and plans for future
sessions. Sessions will be audio taped so relevant points can be discussed in
supervision. Ratings of audiotapes will be conducted by the PIs for 25% of the
sessions, based on a list of key components.

Frequent staff trainings is the key to delivering interventions as intended and to
prevent drift. Therefore, staff training will occur twice annually in years 1-3 and
once annually in years 4-5. Study PIs will coordinate the trainings which will be
delivered collectively by the PIs and co-investigators. Training will cover delivery of
the prevention program, coordinator activities (e.g., processing of blood samples for
A1c), and treatment fidelity.

3. Risks: The risks in this study should be minor as many of the intervention components
have been employed previously in research and clinical settings with minimal adverse
events. The risks that come along with any study in which emotional and behavioral
factors are discussed include the possibility of discomfort when completing
questionnaires and during discussions in the intervention sessions. Further, given the
nature of diabetes management, stress or patient-parent conflict may occur when
uncontrolled blood sugars are documented. The research staff is trained to identify
such distress or discomfort early and provide support in the intervention. Patients
agreeing to participate in the studies will experience the usual risks associated with
the treatment of type 1 diabetes: the most significant risk is hypoglycemia, which is
present for all patients undergoing treatment for diabetes with insulin.

Another risk associated with this study is the threat to privacy and confidentiality if the
secured website is somehow breached. However the SNAP software system and the secured
web-site has been reviewed and approved by CMH's IT officers (Ron Isbell and Jason Ruprecht)
and CMH's PHI officer (Valerie Witmer), and the PI has been using this secured website in
another study without difficulties. Participants will access the questionnaires through the
secured web-site and each participant will be assigned a unique study ID code number. Names,
initials or other identifying information will not be used on any of the measures.

There may be other unknown risks for which investigators will monitor. An additional risk is
the potential threat to privacy and confidentiality. Investigators believe that these
represent minimal risks as defined by the DHHS office of Human Research Protection.

Inclusion Criteria:

Study participants will meet the following inclusion criteria:

- 14-18 years old,

- diagnosis of T1D according to ADA criteria for at least 1 year,

- daily insulin dosing of at least 0.5 units per kilogram per day,

- fluent in English, and

- provide assent to participate.

Exclusion Criteria:

- other chronic, physical disease or condition except for celiac or thyroid disease,

- diagnosis of major depressive disorder determined at screening visit,

- current treatment with an antidepressant,

- diagnosis of major mental disorder (e.g., bipolar disorder, thought disorder,
anorexia nervosa),

- diagnosis of developmental disorder (e.g., mental retardation, autism, asperger's),
or ward of the state.

Adolescents must have established T1D, uncomplicated by other chronic diseases so any
observed changes in glycemic control during the study cannot be attributed to other
diseases or to endogenous insulin production seen in the 'honeymoon' period.28 Adolescents
cannot have a diagnosis of major depressive disorder because that diagnosis warrants more
intensive intervention. Further, adolescents cannot be on antidepressant medication
treatment at the time they start the trial because it may impact psychological outcomes
and cause unmeasured treatment effects. Finally, adolescents need to be without
developmental or learning problems as that may make participation difficult, especially in
a group format.