Clinical trial NCT02351466: Type 1 Diabetes and the Brain in Children
Official title: Type 1 Diabetes and the Brain in Children: Metabolic Interventions. Protocol #1: Longitudinal Assessment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 1
Keywords: Brain Growth and Development
Cognition
Children
Continuous Glucose Monitoring
MRI
Functional MRI
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
Collaborators: name: Stanford University
name: Washington University School of Medicine
name: Yale University
name: University of Iowa
First posted: 2015-01-30
Enrollment: 221
Sex: ALL
Minimum age (years): 7
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with Type 1 Diabetes or Healthy non-diabetic controls

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in total and regional gray and white matter volumes and white matter microstructure.
timeFrame: 2 years
Secondary outcomes:
measure: Measures of activation of frontal-parietal networks and functional connectivity of resting state networks using blood oxygen level dependent (BOLD)-functional MRI.
timeFrame: 2 years
measure: Changes in Neurocognitive metrics including IQ as well as executive and visual-spatial memory.
timeFrame: 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Nemours Childrens Clinic
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: Nemours Children's Clinic
name: Nelly Mauras, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Allan L Reiss, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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.
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.
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.
citation: Mauras N, Buckingham B, White NH, Tsalikian E, Weinzimer SA, Jo B, Cato A, Fox LA, Aye T, Arbelaez AM, Hershey T, Tansey M, Tamborlane W, Foland-Ross LC, Shen H, Englert K, Mazaika P, Marzelli M, Reiss AL; Diabetes Research in Children Network (DirecNet). Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study. Diabetes Care. 2021 Apr;44(4):983-992. doi: 10.2337/dc20-2125. Epub 2021 Feb 10.