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Brain Health and Development With T1DM (NewT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03335878
Recruitment Status : Suspended (Due to COVID 19.)
First Posted : November 8, 2017
Last Update Posted : May 12, 2020
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
Type 1 diabetes mellitus (T1DM) is typically diagnosed in childhood and over time can lead to complications affecting the retina, heart, kidneys, peripheral nerves, and more recently appreciated, the brain. Studies consistently find that early age of onset and, to a more variable extent, poor glycemic control over years are associated with reduced cognitive performance and altered brain structure in children with T1DM. As yet, the investigators' understanding of why early age of onset would pose more risks for the brain is limited, making interventions difficult to develop. Given that the initial clinical presentation of T1DM in children is the earliest and often the most severe glycemic state experienced over the lifetime, it is possible that age of onset and severity of initial clinical presentation interact to modify risks for brain health and development. This hypothesis has clear clinical implications and the potential to resolve conflicting literature, yet has not been explicitly tested. Thus, the goal of this study is to determine how clinical features at the time of T1DM diagnosis, such as hyperglycemia, diabetic ketoacidosis (DKA) and degree of beta cell failure, interact with age of onset to shape the development of the brain and its responses to subsequent glycemic control.

Condition or disease
T1DM Brain Development

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Early Predictors of Brain Health and Development in Youth With T1DM
Actual Study Start Date : September 1, 2016
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : September 2, 2021

Group/Cohort
Type 1 Diabetes Mellitus Group
T1DM Group - 150 otherwise healthy children, ages 4-16 years old, diagnosed with T1DM within 3 months prior to their initial study visit. This is not a treatment study therefore there is no intervention in this study.
Healthy Control Sibling Group
Sibling Control Group - 50 age and gender matched healthy siblings without a diagnosis of T1DM. This is not a treatment study therefore there is no intervention in this study.



Primary Outcome Measures :
  1. Scaled score on Verbal IQ tests at 18 months [ Time Frame: 18 months ]
    The investigators hypothesize that age of onset and severity of presentation will interact to explain neuroimaging and cognitive outcomes at 3 months post-diagnosis. Specifically, the study investigators predict that patients with earlier age of onset and greater severity of clinical presentation (presence of DKA, greater HbA1c values at diagnosis) will have lower performance and more atypical brain structure and functional connectivity compared to older patients with less severe presentation and to age-matched controls, after controlling for gender, parental socioeconomic status (SES), parental IQ and intervening glycemic control. Primary neuroimaging outcomes are hippocampal volume and regional gray matter volume, microstructural white matter parameters and functional connectivity of the default mode network. Primary cognitive outcomes are memory and verbal intelligence.


Secondary Outcome Measures :
  1. Functional Connectivity of the Default Mode Network at 18 months [ Time Frame: 18 months ]
    The study investigators hypothesize that the development of the brain between 3 and 21 months post-diagnosis will be differently affected by severity of clinical presentation and glycemic control during follow-up. Specifically, the study investigators predict that greater severity of clinical presentation will convey greater vulnerability to subsequent hyperglycemia and severe hypoglycemia. For example, those individuals with a severe clinical presentation and significant hyperglycemia post-diagnosis will have worse outcomes on the cognitive and neuroimaging variables identified in Aim 1.

  2. Hippocampal Volume at 18 months [ Time Frame: 18 months ]
    Retrospective studies suggest that lower β-cell function uniquely predicts future long-term complications such as retinopathy, above and beyond the effects of glycemic control and duration of disease. Thus, β-cell function also may be a physiologic mediator of brain outcomes. However, prospective studies have not been conducted in newly diagnosed T1DM youth to establish that this pattern holds for the brain. Study investigators hypothesize that patients with lower β-cell function (assessed through a mixed meal tolerance test, MMTT) will be more likely to have brain and cognitive differences (identified in Aim 1) compared to those with higher β-cell function, after controlling for age, gender, parental SES, parental IQ and glycemic control.

  3. White Matter Microstructure at 18 months [ Time Frame: 18 months ]

Biospecimen Retention:   Samples Without DNA
Participants will undergo a Mixed Meal Tolerance Test (MMTT) for assessment of residual β-cell function. A dose of Boost High Protein Nutritional Energy Drink (Mead-Johnson) mixed meal at 6 mL/kg (maximum dose 360 mL) will be given at 0 min. Blood samples will be obtained for measurement of plasma glucose and C-peptide at −10, 0, 15, 30, 60, 90, 120, 150, 180, 210, and 240 min. A split duplicate sample for quality control will be collected at either 0 or 240 min.


Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

There are three study groups in this study.

  1. T1DM Group (n=150) Children between the ages of 4-16 yrs old who have been diagnosed with Type 1 Diabetes Mellitus (T1DM) in the past three months.
  2. Sibling Control Group (n=50) Children between the ages of 4-16 yrs old who are siblings of children with T1DM and who have NOT been diagnosed with T1DM themselves.
  3. Proxies (n=200) a parent or guardian of participants in one or both groups. The number of proxies in the study could exceed the number of minor participants because not all sibling controls have to be a sibling of a T1DM participant in the study. They may have a sibling with T1DM who doesn't meet the criteria for the study.
Criteria

T1DM Group

Inclusion Criteria:

  • Otherwise healthy children with T1DM
  • Between the ages of 4 to 16 years old
  • Must be able to lie still in the MRI for 60 minutes

Exclusion Criteria:

  • Mental retardation
  • Enrollment in special education classes or receiving special services
  • Major psychiatric (e.g. depression, autism) or neurological illnesses (e.g. head injury with loss of consciousness)
  • Currently taking medications with known central nervous system effects (including those for ADHD)
  • Physical limitations that would interfere with testing
  • Contraindications for MRI scans
  • Females who are pregnant and/or lactating will be excluded
  • Chronic diseases in addition to T1DM other than well-controlled asthma, celiac disease or Hashimoto's thyroiditis as determined by their clinical endocrinologist and/or nurse

Sibling Control Group

Inclusion Criteria:

  • Healthy sibling of a T1DM participant
  • Matched with a T1DM participant for age and gender
  • Between the ages of 4 to16 years old
  • Must be able to lie still in the MRI for 60 minutes

Exclusion Criteria

  • Mental retardation
  • Enrollment in special education classes or receiving special services
  • Major psychiatric (e.g. depression, autism) or neurological illnesses (e.g. head injury with loss of consciousness)
  • Currently taking medications with known central nervous system effects (including those for ADHD)
  • Physical limitations that would interfere with testing
  • Contraindications for MRI scans
  • Females who are pregnant and/or lactating will be excluded
  • Chronic diseases other than well-controlled asthma, celiac disease or Hashimoto's thyroiditis as determined by their clinical endocrinologist and/or nurse.

The Parent population will consist of one biological parent for each minor participant. The proxy participant will complete two neuropsychological tests as well as answer questionnaires about the minor study participant. The parent population has no age limitations but must be a biological parent to the minor study participant. The testing takes approximately 20 minutes thus the parent population will not be paid for their participation.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03335878


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Tamara G Hershey, PhD Washington University Medical School
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03335878    
Other Study ID Numbers: 201601135
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: May 12, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After data is collected and entered into the REDCap database (which includes de-identifying any data) and the database is locked, the PI will then consider sharing the data with collaborators who are interested.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No