Objective
Following the ORBIT model, this application proposes to: 1) Adapt a brief cognitive-behavioral treatment previously shown to effectively reduce anxiety in children and adults for youth and caregivers experiencing anxiety about developing T1D (ORBIT Phase 1) and 2) Conduct a proof-of-concept study, iteratively testing the adapted treatment on a small sample of adolescents and parents with high anxiety about the adolescent’s T1D risk (ORBIT Phase 2a).
Phase 1: Adapt brief cognitive-behavioral therapy (CBT) treatment for youth and their caregivers who are experiencing high anxiety in response to the news that they (or their child) are islet autoantibody positive (IA+) and consequently at high risk for T1D. The intervention (“CBT-PreT1D”) will be delivered using telehealth. We will conduct semi-structured interviews with key stakeholders: highly anxious youth >10 years of age with pre-symptomatic T1D and highly anxious parents of children with pre-symptomatic T1D to adapt CBT to meet the needs of this specific population. A particular emphasis on understanding the experience of racial and ethnic minorities, and any adaptations needed to ensure a culturally sensitive intervention, will be accomplished by pre-specifying recruitment targets for individuals from racial and ethnic minority backgrounds. A facilitator manual, youth workbook, and caregiver workbook for CBT-PreT1D will be developed through this process for use in phases 2 and 3.
Phase 2: Conduct single-arm proof-of-concept testing to determine if CBT-PreT1D can achieve a reduction in anxiety about T1D risk in both youth and caregivers. We will use iterative testing and adaptation where we conduct the intervention with a cohort of participants, refine the intervention as needed, and then conduct with a new cohort until we are satisfied with the intervention and it is acceptable and feasible across participant subgroups (by ethnicity ang age).
If the aims of this project are achieved, we will be extremely well positioned to test the developed intervention in a randomized controlled trial. Access to an intervention to address anxiety in pre-symptomatic T1D will advance the field given that concern about anxiety is currently a significant barrier to screening for IA.
Background Rationale
T1D is characterized by an autoimmune process that attacks the insulin-producing beta cells in the pancreas, leaving the affected individual reliant on exogenous insulin for survival. At diagnosis, individuals often present with weight loss, polydipsia, polyuria and in severe cases, diabetic ketoacidosis (DKA). Without timely intervention, DKA can be life-threatening. However, the disease process begins well before, often years before, these clinical symptoms present. Positive islet autoantibodies (IA) indicate that deterioration has begun of the beta cells that produce insulin. During the pre-symptomatic period, individuals eventually start exhibiting signs of dysglycemia (i.e., elevated glucose values); at this point, individuals have a 75% 5-year risk of developing clinical T1D and a near 100% lifetime risk. A clinical diagnosis of T1D is confirmed once the individual develops hyperglycemia per American Diabetes Association criteria. There is currently no cure for T1D. Yet, early detection of positive IAs offers the potential of interrupting or delaying the autoimmune process when it is still in its early stages. Recognizing this, developing universal screening is a top priority for the JDRF.
Historically, screening for IA has been conducted in research settings and mostly amongst high-risk individuals, determined to be high-risk because they have first-degree relatives with T1D or have been determined to have an increased genetic risk. The lack of successful T1D prevention strategies has been a major argument against widespread general population screening. However, in November 2022, the FDA approved the first ever pharmacologic agent (tepluzimab) to delay the onset of clinical T1D in individuals ≥ 8 years of age who are multiple IA+ with dysglycemia (i.e., stage 2 T1D). As such, it is reasonable to expect a significant increase in screening now that there is an approved intervention to delay the onset of clinical (i.e., stage 3 T1D). In fact, screening for IA is now rapidly increasing internationally in individuals without a family history of T1D or increased genetic risk, referred to as “general population.” In addition, the American Diabetes Association recently changed their position on IA screening for T1D risk and now considers it appropriate outside of clinical research settings for first-degree relatives of individuals with T1D.
Events that are unpredictable, uncontrollable, and threatening are stressful. There is no cure for T1D and currently, there is no way to prevent it. Consequently, learning that you or your child is at-risk for T1D is stressful because when or even if you or your child will get the disease is unknown. Caregiver anxiety is highest at initial notification of the child’s increased genetic risk for T1D. However, caregiver anxiety declines over time, particularly for those whose children remain IA negative. The majority of parents of IA positive children, who are at very high risk for developing T1D, tend to experience persistent anxiety. Cognitive-behavioral therapy (CBT) is the first-line treatment for anxiety disorders and has the most evidence of efficacy; this treatment focuses on addressing maladaptive thoughts while increasing engagement in activities previously avoided due to anxiety. CBT has been applied to individuals experiencing a variety of anxiety provoking serious medical conditions such as cancer, myocardial infraction, and kidney disease requiring a transplant, among others. CBT has also been adapted for use in a variety of settings including schools, telehealth, and through parent training.29 CBT for anxiety has been well studied in adults, adolescents, and children. CBT has also been used in individuals with T1D. However, there are currently NO studies examining psychological interventions to address anxiety in the pre-symptomatic T1D period which is highly concerning given the high rates of anxiety in this population and the push for universal IA screening.
Description of Project
Screening for islet autoantibodies (IA) has historically been conducted in research settings, primarily amongst youth determined to be at high-risk for type 1 diabetes (T1D) on account of having first-degree relatives with T1D and/or high genetic risk. Recently, screening for IA in the general population has been increasing and it is reasonable to expect a significant increase in IA screening now that there is an approved intervention to delay the onset of clinical (i.e., stage 3) T1D.
Decades of research demonstrate that anxiety is a common parent/caregiver reaction to being told one’s child is at risk for T1D, appreciably because T1D is an uncertain, unpredictable, and threatening chronic disease. Previous research also has highlighted that anxiety about that risk may be a determinant of suboptimal retention and compliance in programs monitoring IA positive children for progression to clinical T1D, which is concerning given that compliance and retention are critical to realizing the benefits of pre-symptomatic T1D monitoring programs. Although there are surprisingly limited data on children’s own perspectives of such programs, preliminary data indicate a high percentage (36%-78%) report feeling highly anxious about their risk for developing T1D. There are currently no studies examining psychological interventions to address anxiety in the pre-symptomatic T1D period, despite the high rates of caregiver and youth anxiety. Given the focus on universal IA screening, there is an urgent need for a culturally sensitive, pragmatic, and evidence-based intervention to address anxiety caused by screening and knowledge of one’s risk (or child’s risk) for T1D. Therefore, the overarching aim of this JDRF Career Development Award is to use a mixed-methods approach to adapt an evidence-based intervention for anxiety, cognitive-behavioral therapy, for youth at high risk for developing T1D (IA positive) and their parents/caregivers who are experiencing high anxiety about such risk.
Anticipated Outcome
The overarching aim of this proposal is to use mixed-methods to develop an evidence-based cognitive-behavioral intervention adapted to meet the specific needs of youth with pre-symptomatic T1D and their caregivers experiencing anxiety about T1D risk.
Phase 1: The anticipated outcome for phase 1 is a facilitator treatment manual, youth workbook and caregiver workbook ready for testing.
Phase 2: The anticipated outcome is average post-treatment change/confidence intervals for caregiver and child anxiety about T1D. Mean, median, 25th/75th percentiles of change scores and confidence intervals for state anxiety about T1D risk will be calculated. We anticipate that most (>70%) of participants will have some decline in state anxiety about T1D risk between pre-intervention assessment and post-intervention assessment. In addition, we will measure acceptability and feasibility by % eligible participants who enroll, # sessions attended, a treatment satisfaction questionnaire, % participants who complete treatment, % participants who complete post-treatment assessments, # days between assessments sent and assessments completed, and % assessments with missing data.
If the aims of this project are achieved, we will be extremely well positioned to test the developed intervention in a randomized controlled trial. Access to an intervention to address anxiety in pre-symptomatic T1D will advance the field given that concern about anxiety is currently a significant barrier to screening for IA.
Relevance to T1D
T1D is one of the most common chronic diseases of childhood, second only to asthma. Unfortunately, incidence of T1D is only increasing. T1D is characterized by an autoimmune process that attacks the insulin-producing beta cells in the pancreas, leaving the affected individual reliant on exogenous insulin for survival. At diagnosis, individuals often present with weight loss, polydipsia, polyuria and in severe cases, diabetic ketoacidosis (DKA). Without timely intervention, DKA can be life-threatening. However, the disease process begins well before, often years before, these clinical symptoms present. Positive islet autoantibodies (IA) indicate that deterioration has begun of the beta cells that produce insulin. During the pre-symptomatic period, individuals eventually start exhibiting signs of dysglycemia (i.e., elevated glucose values); at this point, individuals have a 75% 5-year risk of developing clinical T1D and a near 100% lifetime risk. A clinical diagnosis of T1D is confirmed once the individual develops hyperglycemia per American Diabetes Association criteria. There is currently no cure for T1D. Yet, early detection of positive IAs offers the potential of interrupting or delaying the autoimmune process when it is still in its early stages. Recognizing this, developing universal screening is a top priority for the JDRF: Goal 1 in the JDRF Research Strategy is to “develop and execute a global universal screening strategy that reduces DKA at diagnosis, identifies high-risk individuals for early detection and accelerate the evaluation of disease-modifying therapies, identify individuals that will be eligible for approved preventive treatments, and in conjunction develop cost-benefit analyses of screening for payer assessment.”
Learning that you or your child is at-risk for T1D is stressful because when or even if you or your child will get the disease is unknown. The majority of parents of IA positive children, who are at very high risk for developing T1D, tend to experience persistent anxiety. Cognitive-behavioral therapy (CBT) is the first-line treatment for anxiety disorders and has the most evidence of efficacy; this treatment focuses on addressing maladaptive thoughts while increasing engagement in activities previously avoided due to anxiety. CBT has been applied to individuals experiencing a variety of anxiety provoking serious medical conditions such as cancer, myocardial infraction, and kidney disease requiring a transplant, among others. CBT has also been adapted for use in a variety of settings including schools, telehealth, and through parent training. CBT for anxiety has been well studied in adults, adolescents, and children. CBT has also been used in individuals with T1D. However, there are currently NO studies examining psychological interventions to address anxiety in the pre-symptomatic T1D period. The proposed project aims to address this gap in the literature by developing and conducting pilot testing for an evidence-based CBT intervention adapted to address the specific needs of IA+ youth and their caregivers who are highly anxious about T1D risk. Addressing anxiety about T1D risk will help advance the JDRF mission to “develop and execute a universal screening program” as anxiety about T1D risk is currently a barrier to increasing screening.