NCT02351466

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
221

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2015

Typical duration for all trials

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 27, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 30, 2015

Completed
1 month until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

October 22, 2020

Status Verified

October 1, 2020

Enrollment Period

3.7 years

First QC Date

January 27, 2015

Last Update Submit

October 20, 2020

Conditions

Diabetes Mellitus, Type 1

Keywords

Brain Growth and DevelopmentCognitionChildrenContinuous Glucose MonitoringMRIFunctional MRI

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • Measures of activation of frontal-parietal networks and functional connectivity of resting state networks using blood oxygen level dependent (BOLD)-functional MRI.

    2 years

  • Changes in Neurocognitive metrics including IQ as well as executive and visual-spatial memory.

    2 years

Study Arms (2)

Children with Type 1 Diabetes

Subjects with T1 diabetes will undergo a physical exam and blood test as well as structural and functional brain MRI, neurocognitive testing and wear a continuous glucose monitor every 3 months for 24 months.

Other: Observational

Healthy Controls

Subjects will undergo a physical exam and blood test as well as structural and functional brain MRI at baseline and after 24 months.

Other: Observational

Interventions

ObservationalOTHER
Children with Type 1 DiabetesHealthy Controls

Eligibility Criteria

Age7 Years - 16 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

Children with Type 1 Diabetes or Healthy non-diabetic controls

You may qualify if:

  • Diabetes diagnosed after age 6 months
  • Gestational age \>34 weeks, birth weight \>2kg
  • Normal HbA1C and fasting blood glucose
  • Negative diabetes auto-antibodies (those that are siblings of T1D patients)
  • Gestational age \>34 weeks, birth weight \>2kg

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Stanford University

Palo Alto, California, 94305, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Nemours Childrens Clinic

Jacksonville, Florida, 32207, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

Washington University

St Louis, Missouri, 63126, United States

Location

Related Publications (7)

  • 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.

    PMID: 25488901BACKGROUND

  • 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.

    PMID: 24512675BACKGROUND

  • 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.

    PMID: 24319123BACKGROUND

  • 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.

    PMID: 24170697BACKGROUND

  • 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.

    PMID: 24096802BACKGROUND

  • 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.

    PMID: 25496062BACKGROUND

  • 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.

    PMID: 33568403DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health CareOutcome and Process Assessment, Health CareQuality of Health CareHealth Services Administration

Study Officials

  • Nelly Mauras, MD

    Nemours Children's Clinic

    PRINCIPAL INVESTIGATOR

  • Allan L Reiss, MD

    Stanford University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

January 27, 2015

First Posted

January 30, 2015

Study Start

March 1, 2015

Primary Completion

November 1, 2018

Study Completion

December 1, 2018

Last Updated

October 22, 2020

Record last verified: 2020-10

Locations

US(5)