Type 1 Diabetes and the Brain in Children

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

Type 1 Diabetes and the Brain in Children: Metabolic Interventions. Protocol #1: Longitudinal Assessment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02351466
• Other study ID #: 588973
• Status: Completed
• Start date: March 2015
• Est. completion date: December 2018

Study information

• Verified date: October 2020
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators have previously studied a group of young children with T1D using brain MRI, age-appropriate neurocognitive testing and continuous glucose monitoring, followed for 18 months. The investigators observed significant differences in gray matter volumes and white matter microstructure in the children with diabetes as compared to controls. These differences appeared to increase over time, with slower rates of brain growth in the T1D group (Mazelli, et al, Diabetes 2014; Barnea-Goraly, et al, Diabetes Care 2014; Mauras, et al, Diabetes 2015). In this new protocol the investigators will include the same children with T1D and healthy controls previously studied and recruit new similar subjects to replace those lost by attrition. The investigators will be using structural and functional brain MRI, neurocognitive testing and measures of glycemic control, to determine if changes in the brain persist or worsen over longitudinal follow up, and whether these changes are associated with measures of glycemic control and neurocognitive metrics as these children grow and progress through puberty.

Description:

Study participation will last about 2 to 2 1/12 years and will include a brain MRI without sedation, as well as a functional MRI and neurocognitive testing. The children with T1D will wear a continuous glucose monitor (CGM), will follow up every 3 months and will be asked to wear the CGM each time. The structural and functional MRI and neurocognitive testing will be repeated 2 yrs from baseline.

The healthy controls will also undergo MRI and cognitive testing as well as have a blood sample at baseline and after 2 years.

Parents of newly recruited subjects will also have abbreviated IQ testing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: December 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Years to 16 Years

Eligibility

Inclusion Criteria for T1 Diabetes Group:

• Diabetes diagnosed after age 6 months

• Gestational age >34 weeks, birth weight >2kg

Inclusion Criteria for Healthy Control Group:

• Normal HbA1C and fasting blood glucose

• Negative diabetes auto-antibodies (those that are siblings of T1D patients)

• Gestational age >34 weeks, birth weight >2kg

Exclusion Criteria for Both Groups:

• History of mental retardation, language or learning disability

• Known genetic or medical problem that could impair brain development

• Abnormality of the brain/nervous system, visual or hearing problem

• History of seizures not associated with fever

• Previous inpatient psychiatric treatment

• Unable to have a MRI of the head due to metal appliances

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Other:
• Observational

Locations

Country	Name	City	State
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	Nemours Childrens Clinic	Jacksonville	Florida
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Washington University	Saint Louis	Missouri

Sponsors (5)

Lead Sponsor	Collaborator
Nemours Children's Clinic	Stanford University, University of Iowa, Washington University School of Medicine, Yale University

Country where clinical trial is conducted

United States, 

References & Publications (6)

Barnea-Goraly N, Raman M, Mazaika P, Marzelli M, Hershey T, Weinzimer SA, Aye T, Buckingham B, Mauras N, White NH, Fox LA, Tansey M, Beck RW, Ruedy KJ, Kollman C, Cheng P, Reiss AL; Diabetes Research in Children Network (DirecNet). Alterations in white matter structure in young children with type 1 diabetes. Diabetes Care. 2014 Feb;37(2):332-40. doi: 10.2337/dc13-1388. Epub 2013 Dec 6. — View Citation

Barnea-Goraly N, Weinzimer SA, Ruedy KJ, Mauras N, Beck RW, Marzelli MJ, Mazaika PK, Aye T, White NH, Tsalikian E, Fox L, Kollman C, Cheng P, Reiss AL; Diabetes Research in Children Network (DirecNet). High success rates of sedation-free brain MRI scanning in young children using simple subject preparation protocols with and without a commercial mock scanner--the Diabetes Research in Children Network (DirecNet) experience. Pediatr Radiol. 2014 Feb;44(2):181-6. doi: 10.1007/s00247-013-2798-7. Epub 2013 Oct 6. — View Citation

Cato MA, Mauras N, Ambrosino J, Bondurant A, Conrad AL, Kollman C, Cheng P, Beck RW, Ruedy KJ, Aye T, Reiss AL, White NH, Hershey T; Diabetes Research in Children Network (DirecNet). Cognitive functioning in young children with type 1 diabetes. J Int Neuropsychol Soc. 2014 Feb;20(2):238-47. doi: 10.1017/S1355617713001434. — View Citation

Marzelli MJ, Mazaika PK, Barnea-Goraly N, Hershey T, Tsalikian E, Tamborlane W, Mauras N, White NH, Buckingham B, Beck RW, Ruedy KJ, Kollman C, Cheng P, Reiss AL; Diabetes Research in Children Network (DirecNet). Neuroanatomical correlates of dysglycemia in young children with type 1 diabetes. Diabetes. 2014 Jan;63(1):343-53. doi: 10.2337/db13-0179. Epub 2013 Oct 29. — View Citation

Mauras N, Mazaika P, Buckingham B, Weinzimer S, White NH, Tsalikian E, Hershey T, Cato A, Cheng P, Kollman C, Beck RW, Ruedy K, Aye T, Fox L, Arbelaez AM, Wilson D, Tansey M, Tamborlane W, Peng D, Marzelli M, Winer KK, Reiss AL; Diabetes Research in Children Network (DirecNet). Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes. 2015 May;64(5):1770-9. doi: 10.2337/db14-1445. Epub 2014 Dec 8. — View Citation

Tansey M, Beck R, Ruedy K, Tamborlane W, Cheng P, Kollman C, Fox L, Weinzimer S, Mauras N, White NH, Tsalikian E; Diabetes Research in Children Network (DirecNet). Persistently high glucose levels in young children with type 1 diabetes. Pediatr Diabetes. 2016 Mar;17(2):93-100. doi: 10.1111/pedi.12248. Epub 2014 Dec 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in total and regional gray and white matter volumes and white matter microstructure.	Structural MRIs of children with T1 diabetes will be compared to age- and sex-matched, non-diabetic healthy controls. We will investigate whether these changes are associated with measures of glycemic control and neurocognitive metrics as these children grow and progress through puberty. The present cohorts (T1D and controls) of young children will be followed for 2 more years with similar studies repeated 2 years apart. Overall glycemic profiles will continue to be obtained every 3 months longitudinally between scans with CGM and HbA1c for children with Type 1 Diabetes.	2 years
Secondary	Measures of activation of frontal-parietal networks and functional connectivity of resting state networks using blood oxygen level dependent (BOLD)-functional MRI.		2 years
Secondary	Changes in Neurocognitive metrics including IQ as well as executive and visual-spatial memory.	We will perform neurocognitive metrics reflecting frontal, parietal-occipital and hippocampal function. Children with T1D will be followed longitudinally and compared with controls to determine whether these differences are associated with measures of glycemic control.	2 years