Glycemic Control and the Brain in Children With Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

Official title:

Glycemic Control and the Brain in Children With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03428932
• Other study ID #: 00000766
• Status: Completed
• Phase: N/A
• Start date: February 1, 2018
• Est. completion date: July 1, 2019

Study information

• Verified date: July 2019
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: July 1, 2019
• Est. primary completion date: July 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Device:
• Closed Loop (Medtronic 670G)
A loaner Medtronic 670G insulin pump, Enlite 3 sensor and GST3C Guardian transmitter will be utilized

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

Locations

Country	Name	City	State
United States	University of Iowa	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 St. Louis	Saint Louis	Missouri

Sponsors (7)

Lead Sponsor	Collaborator
Nemours Children's Clinic	Jaeb Center for Health Research, National Institutes of Health (NIH), Stanford University, University of Iowa, Washington University School of Medicine, Yale University

Country where clinical trial is conducted

United States, 

References & Publications (11)

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

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. — 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

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. — View 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. — View 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. — View 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. — 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

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. — View 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Gray Matter Volume in the Brain	Trends in total and regional grey matter volume	6 months
Secondary	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.	6 months
Secondary	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.	6 months