Pediatric Type 1 Diabetes and Neurocognitive Complications Cohort Study

Completed

• Conditions: Type 1 Diabetes
• Interventions: Behavioral: neurocognitive assessment; Behavioral: neuroimaging assessment

• Registration Number: NCT04135365
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

The proposed project will assess hypothesized risk factors (age of onset, Diabetic ketoacidosis (DKA) at presentation and glycemic control), as well as potentially modifiable protective factors (child sleep quality, caregiver distress, and use of diabetes devices). In addition, the study will optimize imaging protocols and processing tools to allow for harmonization of neuroimaging data across sites and scanners for the most robust analysis.

Detailed Description

The onset of type 1 diabetes (T1D) in childhood results in clinically significant deficits in neurocognitive functioning that manifest in adulthood. These deficits have implications for adaptive functioning and diabetes management. Studies of neurocognitive function and brain development in T1D suggest that factors such as age of onset, diabetic ketoacidosis (DKA) at time of onset, and exposure to chronic hyperglycemia or severe hypoglycemia may increase risk or severity of these deficits, but findings are mixed. The majority of previous studies were limited by the use of adult or older adolescent samples, cross-sectional designs or short duration of follow-up, lack of racial and ethnic diversity, and small sample sizes. Age-related changes in neurocognitive function and vascular complications associated with T1D in adults make isolating mechanisms more complex. The knowledge gaps are critical because individuals with T1D may live for decades with reduced neurocognitive function. Building on previous work, it is hypothesized that several risk and protective factors for neurocognitive deficits will be evident in youth with T1D. First, sleep is a critical and potentially modifiable risk or protective factor for youth. Prior work has shown that the majority of school-age children do not obtain sufficient sleep (67%), and that sleep disturbances are related to poor glycemic control and risk for DKA, both of which have been posited to increase risk for neurocognitive deficits. Second, caregiver distress (i.e., symptoms of anxiety and depression) is a significant risk factor for child wellbeing, as exposure to maternal depressive symptoms increases children's risk for cognitive deficits and abnormal white matter diffusivity. Third, improved glycemic control via use of continuous glucose monitors and hybrid closed-loop insulin delivery systems, are potential protective factors for youth with T1D, as these devices decrease glycemic variability and limit time spent in hypoglycemia and hyperglycemia. Thus, a prospective longitudinal cohort study of young children with T1D is needed to identify modifiable risk and protective factors for neurocognitive complications. If specific risk or protective factors for adverse or optimal neurocognitive outcomes are defined, treatment protocols could be developed to limit neurocognitive complications associated with T1D.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-10-17
• Study First Submitted QC: 2019-10-18
• Study First Posted: 2019-10-22
• Study Start: 2021-01-18
• Status Verified: 2022-10
• Primary Completion: 2022-10-31
• Study Completion: 2022-10-31
• Last Update Submitted: 2022-10-31
• Last Update Posted: 2022-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Pediatric T1D sample: Children will be eligible if they meet the following inclusion/exclusion criteria:

  1. are between 6 -11 years of age
  2. have no history of afebrile seizure (not related to hypoglycemia) or sleep disorders other than insufficient sleep or insomnia
  3. no contraindications to high quality MRI of the brain (no metal implants or braces)
  4. no premature birth (<34 weeks) or low birth weight (<2,000g).

Comparison sample: Children will be eligible if they meet the following inclusion/exclusion criteria:

1. no known chronic medical conditions or intellectual disability
2. no known history of concussion or traumatic brain injury
3. no history of afebrile seizure; (4) no braces or metal implants

(5) no premature birth (<34 weeks) or low birth weight (<2,000g).

Parents or primary caregivers of all children will be eligible if they:

1. live with the child
2. read/speak English to allow use of validated parental questionnaires. The parent who is the primary caregiver of the child will be invited to participate.

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Exclusion Criteria

• N/A

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Comparison	neurocognitive assessment	Children with no known chronic medical conditions or intellectual disability will undergo the same procedure listed for the Pediatric T1D group
Comparison	neuroimaging assessment	Children with no known chronic medical conditions or intellectual disability will undergo the same procedure listed for the Pediatric T1D group
Pediatric T1D	neuroimaging assessment	A sample of 20 children with Type 1 Diabetes and their caregivers will be asked to stay after their diabetes clinic appointment to complete enrollment, or they may choose to come back for a study visit. Trained study staff will describe the study in detail to interested families. They will be encouraged to ask questions before giving consent. After obtaining informed consent/assent, children and caregivers will schedule time for a neurocognitive assessment and neuroimaging assessment. Children and caregivers will complete assessments again approximately 12 months later.
Pediatric T1D	neurocognitive assessment	A sample of 20 children with Type 1 Diabetes and their caregivers will be asked to stay after their diabetes clinic appointment to complete enrollment, or they may choose to come back for a study visit. Trained study staff will describe the study in detail to interested families. They will be encouraged to ask questions before giving consent. After obtaining informed consent/assent, children and caregivers will schedule time for a neurocognitive assessment and neuroimaging assessment. Children and caregivers will complete assessments again approximately 12 months later.

Primary Outcome Measures

Name	Time	Method
Cognitive Function: Behavior Rating Inventory of Executive Function, Second Edition	12 months	Parent report of child's executive function, has been validated for use in children ages 5-18 years. Scaled T-scores are based on normative data for age and sex. The BRIEF2 consists of 63 items, and it yields a Global Executive Composite score, as well as a Behavior Regulation Index, Emotional Regulation Index, and Cognitive Regulation Index
Cognitive Function: Full-scale IQ	12 months	To assess cognitive differences in full-scale IQ using the Wechsler Intelligence Scale for Children, fifth edition (WISC V) in children with T1D vs. comparison children. The Full-Scale IQ is an estimate of overall intellectual ability. The WISC-V takes approximate 48 minutes to administer. The FSQI uses a standard score metric with a mean of 100 and an Standard Deviation of 15.
Cognitive Function: Executive Function	12 monnths	To assess cognitive differences in executive function using the The NIH Toolbox Executive Function Tests in children with T1D vs. comparison children.; 1) NIH Flanker Inhibitory Control and Attention Test will be used to assess children's ability to inhibit visual attention. Average administration time is 4 minutes. A scoring algorithm integrates accuracy, a suitable measure in early childhood, yielding scores from 0 to 10.

Secondary Outcome Measures

Name	Time	Method
Imaging	12 months	Differences in brain volume and white matter microstructure in children with T1D vs comparison children.

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States