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Glycemic Control and the Brain in Children With Type 1 Diabetes

Primary Purpose

Type 1 Diabetes Mellitus

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Closed Loop (Medtronic 670G)

Standard Care

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Insulin pump, Closed loop, Brain development, Pediatric, Type 1 Diabetes, MRI, Cognitive development

Eligibility Criteria

14 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Be at least 14 and not yet 18 years old
Must have been diagnosed with T1D prior to 5 years old but after 6 months
For those diagnosed prior to 1 year of age, a positive blood test for an antibody marker will be required
Have been born term or near term (≥34 weeks) and weighed more than≥ 2 kg (4.4lbs) at birth
Be in puberty

Exclusion Criteria:

History of intellectual disability, language or learning disability identified before diagnosis of diabetes, or enrollment in a self-contained special education program
ADD/ADHD and/or on stimulant medication
Any known genetic or medical problem that could impair brain development
Abnormalities of the brain/nervous system, visual or hearing problem
History of seizures not associated with fever before diabetes diagnosis
Previous inpatient psychiatric treatment
Unable to have a MRI of the head due to having metal: including metal ear tubes, full set of braces in mouth (retainer is acceptable), other appliances, or vascular clip

Sites / Locations

Stanford University
Yale University
Nemours Childrens Clinic
University of Iowa
Washington University St. Louis

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Standard Care

Closed-Loop

Arm Description

Subjects will continue on their current treatment (insulin pump or injections), with follow up every 3 months. Neurocognitive testing and brain MRI/fMRI will be done at enrollment and 6 months.

Subjects will transition from their current treatment (insulin pump or injections) onto the Medtronic 670G insulin pump (intervention arm as a comparator) and will have close contact with the study team. Neurocognitive testing and brain MRI/fMRI will be done at enrollment and 6 months.

Outcomes

Primary Outcome Measures

Changes in Gray Matter Volume in the Brain

Trends in total and regional grey matter volume

Secondary Outcome Measures

Changes in Brain Activation (Dorsal Anterior Cingulate, Inferior Frontal Gyrus and/or Parietal Cortex)

Blood Oxygen level diffusion (BOLD) Functional Magnetic Resonance Imaging (fMRI) was measured to assess functional activation occurring during "no-go" relative to "go" trials during a Go/No-Go cognitive task. Parameter estimates for an individual subject are obtained by modeling the subject's BOLD time series at each voxel against the expected BOLD response to a given task. Statistical weights (i.e., parameter estimates of activation strength) are determined based on how closely the observed and expected signals agree for each task condition to create parameter maps over the entire brain. Higher-level parameter estimates are generated via contrasts of the estimates from specific task conditions, which can lead to positive or negative values, depending on the relative activation of the conditions.

Changes in WASI-II Perceptual Reasoning Index (PRI)

The Wechsler Abbreviated Scale of Intelligence second edition (WASI-II) was used. The WASI-II is composed of four subtests: Block Design, Vocabulary, Matrix Reasoning, and Similarities. The WASI-II used in this study produces a Perceptual Reasoning Index (PRI) score from the Block Design and Matrix Reasoning subtests' age-corrected scaled scores. The index scores are derived from a summation of the comprising scaled scores. The PRI score range is: 50-150. Higher scores mean better outcomes. Change over time in the PRI score is reported in each group.

Full Information

NCT ID

NCT03428932

First Posted

January 24, 2018

Last Updated

April 21, 2023

Sponsor

Nemours Children's Clinic

Collaborators

National Institutes of Health (NIH), Washington University School of Medicine, Stanford University, University of Iowa, Yale University, Jaeb Center for Health Research

1. Study Identification

Unique Protocol Identification Number

NCT03428932

Brief Title

Glycemic Control and the Brain in Children With Type 1 Diabetes

Official Title

Glycemic Control and the Brain in Children With Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

February 1, 2018 (Actual)

Primary Completion Date

July 1, 2019 (Actual)

Study Completion Date

July 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Nemours Children's Clinic

Collaborators

National Institutes of Health (NIH), Washington University School of Medicine, Stanford University, University of Iowa, Yale University, Jaeb Center for Health Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine if improving diabetes control by better controlling blood sugars, will help improve or normalize brain function as compared to routine diabetes care. We will use either the patient's own insulin routine (injections or insulin pumps) or a closed-loop insulin pump (Medtronic 670G). This system uses a continuous glucose monitor (CGM) and an insulin pump to automatically give insulin and may improve control of blood sugars.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus

Keywords

Insulin pump, Closed loop, Brain development, Pediatric, Type 1 Diabetes, MRI, Cognitive development

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

46 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Standard Care

Arm Type

Active Comparator

Arm Description

Subjects will continue on their current treatment (insulin pump or injections), with follow up every 3 months. Neurocognitive testing and brain MRI/fMRI will be done at enrollment and 6 months.

Arm Title

Closed-Loop

Arm Type

Active Comparator

Arm Description

Intervention Type

Device

Intervention Name(s)

Closed Loop (Medtronic 670G)

Intervention Description

A loaner Medtronic 670G insulin pump, Enlite 3 sensor and GST3C Guardian transmitter will be utilized

Intervention Type

Other

Intervention Name(s)

Standard Care

Intervention Description

Subjects will continue on their current treatment (insulin pump or injections), with follow up every 3 months.

Primary Outcome Measure Information:

Title

Changes in Gray Matter Volume in the Brain

Description

Trends in total and regional grey matter volume

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Changes in Brain Activation (Dorsal Anterior Cingulate, Inferior Frontal Gyrus and/or Parietal Cortex)

Description

Time Frame

6 months

Title

Changes in WASI-II Perceptual Reasoning Index (PRI)

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Be at least 14 and not yet 18 years old Must have been diagnosed with T1D prior to 5 years old but after 6 months For those diagnosed prior to 1 year of age, a positive blood test for an antibody marker will be required Have been born term or near term (≥34 weeks) and weighed more than≥ 2 kg (4.4lbs) at birth Be in puberty Exclusion Criteria: History of intellectual disability, language or learning disability identified before diagnosis of diabetes, or enrollment in a self-contained special education program ADD/ADHD and/or on stimulant medication Any known genetic or medical problem that could impair brain development Abnormalities of the brain/nervous system, visual or hearing problem History of seizures not associated with fever before diabetes diagnosis Previous inpatient psychiatric treatment Unable to have a MRI of the head due to having metal: including metal ear tubes, full set of braces in mouth (retainer is acceptable), other appliances, or vascular clip

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nelly Mauras, MD

Organizational Affiliation

Nemours Children's Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University

City

Palo Alto

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

Yale University

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06511

Country

United States

Facility Name

Nemours Childrens Clinic

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32207

Country

United States

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

Washington University St. Louis

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63126

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

In accordance with the NIH data sharing policy, a de-identified database will be placed in the public domain after the completion of the study. This will be timed if possible with publication of the manuscripts that will result from these studies. In addition, formal requests for data will be accepted and reviewed by the DirecNet Steering Committee. If the request is approved, the Data Coordinating Centers will provide the data in a format mutually agreeable to the requesting party.

IPD Sharing Time Frame

After completion of the study

Citations:

PubMed Identifier

21790920

Citation

Bjorgaas MR. Cerebral effects of severe hypoglycemia in young people with type 1 diabetes. Pediatr Diabetes. 2012 Feb;13(1):100-7. doi: 10.1111/j.1399-5448.2011.00803.x. Epub 2011 Jul 25. No abstract available.

Results Reference

background

PubMed Identifier

27702833

Citation

Saggar M, Tsalikian E, Mauras N, Mazaika P, White NH, Weinzimer S, Buckingham B, Hershey T, Reiss AL; Diabetes Research in Children Network (DirecNet). Compensatory Hyperconnectivity in Developing Brains of Young Children With Type 1 Diabetes. Diabetes. 2017 Mar;66(3):754-762. doi: 10.2337/db16-0414. Epub 2016 Oct 4.

Results Reference

background

PubMed Identifier

27339089

Citation

Hosseini SM, Mazaika P, Mauras N, Buckingham B, Weinzimer SA, Tsalikian E, White NH, Reiss AL; Diabetes Research in Children Network (DirecNet). Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes. Hum Brain Mapp. 2016 Nov;37(11):4034-4046. doi: 10.1002/hbm.23293.

Results Reference

background

PubMed Identifier

26512024

Citation

Mazaika PK, Weinzimer SA, Mauras N, Buckingham B, White NH, Tsalikian E, Hershey T, Cato A, Aye T, Fox L, Wilson DM, Tansey MJ, Tamborlane W, Peng D, Raman M, Marzelli M, Reiss AL; Diabetes Research in Children Network (DirecNet). Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes. 2016 Feb;65(2):476-85. doi: 10.2337/db15-1242. Epub 2015 Oct 28.

Results Reference

background

PubMed Identifier

25488901

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.

Results Reference

background

PubMed Identifier

24512675

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.

Results Reference

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PubMed Identifier

24319123

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.

Results Reference

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PubMed Identifier

21953611

Citation

Perantie DC, Koller JM, Weaver PM, Lugar HM, Black KJ, White NH, Hershey T. Prospectively determined impact of type 1 diabetes on brain volume during development. Diabetes. 2011 Nov;60(11):3006-14. doi: 10.2337/db11-0589. Epub 2011 Sep 27.

Results Reference

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PubMed Identifier

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Citation

Ly TT, Breton MD, Keith-Hynes P, De Salvo D, Clinton P, Benassi K, Mize B, Chernavvsky D, Place J, Wilson DM, Kovatchev BP, Buckingham BA. Overnight glucose control with an automated, unified safety system in children and adolescents with type 1 diabetes at diabetes camp. Diabetes Care. 2014 Aug;37(8):2310-6. doi: 10.2337/dc14-0147. Epub 2014 May 30.

Results Reference

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PubMed Identifier

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Citation

Hovorka R, Elleri D, Thabit H, Allen JM, Leelarathna L, El-Khairi R, Kumareswaran K, Caldwell K, Calhoun P, Kollman C, Murphy HR, Acerini CL, Wilinska ME, Nodale M, Dunger DB. Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial. Diabetes Care. 2014;37(5):1204-11. doi: 10.2337/dc13-2644.

Results Reference

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PubMed Identifier

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Citation

Gazdzinski S, Durazzo TC, Mon A, Yeh PH, Meyerhoff DJ. Cerebral white matter recovery in abstinent alcoholics--a multimodality magnetic resonance study. Brain. 2010 Apr;133(Pt 4):1043-53. doi: 10.1093/brain/awp343. Epub 2010 Feb 4.

Results Reference

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PubMed Identifier

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Citation

Reiss AL, Jo B, Arbelaez AM, Tsalikian E, Buckingham B, Weinzimer SA, Fox LA, Cato A, White NH, Tansey M, Aye T, Tamborlane W, Englert K, Lum J, Mazaika P, Foland-Ross L, Marzelli M, Mauras N; Diabetes Research in Children Network (DirecNet) Consortium. A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes. Nat Commun. 2022 Aug 30;13(1):4940. doi: 10.1038/s41467-022-32289-x.

Results Reference

derived

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Glycemic Control and the Brain in Children With Type 1 Diabetes

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