Brain Health and Development With T1DM

NCT03335878 | Completed

• 1 other identifier: 201601135
• Study Type: observational
• Target: 290
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes mellitus (T1DM) is typically diagnosed in childhood and over time can lead to complications affecting the retina, heart, kidneys, peripheral nerves, and more recently appreciated, the brain. Studies consistently find that early age of onset and, to a more variable extent, poor glycemic control over years are associated with reduced cognitive performance and altered brain structure in children with T1DM. As yet, the investigators' understanding of why early age of onset would pose more risks for the brain is limited, making interventions difficult to develop. Given that the initial clinical presentation of T1DM in children is the earliest and often the most severe glycemic state experienced over the lifetime, it is possible that age of onset and severity of initial clinical presentation interact to modify risks for brain health and development. This hypothesis has clear clinical implications and the potential to resolve conflicting literature, yet has not been explicitly tested. Thus, the goal of this study is to determine how clinical features at the time of T1DM diagnosis, such as hyperglycemia, diabetic ketoacidosis (DKA) and degree of beta cell failure, interact with age of onset to shape the development of the brain and its responses to subsequent glycemic control.

Conditions

T1DM; Brain Development

Outcome Measures

Primary Outcomes (1)

• Scaled score on Verbal IQ tests at 18 months

  The investigators hypothesize that age of onset and severity of presentation will interact to explain neuroimaging and cognitive outcomes at 3 months post-diagnosis. Specifically, the study investigators predict that patients with earlier age of onset and greater severity of clinical presentation (presence of DKA, greater HbA1c values at diagnosis) will have lower performance and more atypical brain structure and functional connectivity compared to older patients with less severe presentation and to age-matched controls, after controlling for gender, parental socioeconomic status (SES), parental IQ and intervening glycemic control. Primary neuroimaging outcomes are hippocampal volume and regional gray matter volume, microstructural white matter parameters and functional connectivity of the default mode network. Primary cognitive outcomes are memory and verbal intelligence.

  18 months

Secondary Outcomes (3)

• Functional Connectivity of the Default Mode Network at 18 months

  18 months

• Hippocampal Volume at 18 months

  18 months

• White Matter Microstructure at 18 months

  18 months

Study Arms (2)

Type 1 Diabetes Mellitus Group

T1DM Group - 150 otherwise healthy children, ages 4-16 years old, diagnosed with T1DM within 3 months prior to their initial study visit. This is not a treatment study therefore there is no intervention in this study.

Healthy Control Sibling Group

Sibling Control Group - 50 age and gender matched healthy siblings without a diagnosis of T1DM. This is not a treatment study therefore there is no intervention in this study.

Eligibility Criteria

• Age: 4 Years - 16 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

There are three study groups in this study. 1. T1DM Group (n=150) Children between the ages of 4-16 yrs old who have been diagnosed with Type 1 Diabetes Mellitus (T1DM) in the past three months. 2. Sibling Control Group (n=50) Children between the ages of 4-16 yrs old who are siblings of children with T1DM and who have NOT been diagnosed with T1DM themselves. 3. Proxies (n=200) a parent or guardian of participants in one or both groups. The number of proxies in the study could exceed the number of minor participants because not all sibling controls have to be a sibling of a T1DM participant in the study. They may have a sibling with T1DM who doesn't meet the criteria for the study.

You may qualify if:

• Otherwise healthy children with T1DM
• Between the ages of 4 to 16 years old
• Must be able to lie still in the MRI for 60 minutes

You may not qualify if:

• Mental retardation
• Enrollment in special education classes or receiving special services
• Major psychiatric (e.g. depression, autism) or neurological illnesses (e.g. head injury with loss of consciousness)
• Currently taking medications with known central nervous system effects (including those for ADHD)
• Physical limitations that would interfere with testing
• Contraindications for MRI scans
• Females who are pregnant and/or lactating will be excluded
• Chronic diseases in addition to T1DM other than well-controlled asthma, celiac disease or Hashimoto's thyroiditis as determined by their clinical endocrinologist and/or nurse
• Sibling Control Group
• Healthy sibling of a T1DM participant
• Matched with a T1DM participant for age and gender
• Between the ages of 4 to16 years old
• Must be able to lie still in the MRI for 60 minutes
• Mental retardation
• Enrollment in special education classes or receiving special services

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Participants will undergo a Mixed Meal Tolerance Test (MMTT) for assessment of residual β-cell function. A dose of Boost High Protein Nutritional Energy Drink (Mead-Johnson) mixed meal at 6 mL/kg (maximum dose 360 mL) will be given at 0 min. Blood samples will be obtained for measurement of plasma glucose and C-peptide at -10, 0, 15, 30, 60, 90, 120, 150, 180, 210, and 240 min. A split duplicate sample for quality control will be collected at either 0 or 240 min.

Study Officials

• Tamara G Hershey, PhD

  Washington University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2017
• First Posted: November 8, 2017
• Study Start: September 1, 2016
• Primary Completion: December 6, 2021
• Study Completion: December 6, 2021
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)