Diabetes Mellitus, Type 1NCT02351466
Type 1 Diabetes and the Brain in Children
An observational study of Diabetes Mellitus, Type 1, run by Nemours Children's Clinic at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 16 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Observational
- How many people
- 221 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2015to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 16 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Children with Type 1 Diabetes or Healthy non-diabetic controls
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Nemours Childrens Clinic
Jacksonville, Florida, 32207
Yale University
New Haven, Connecticut, 06511
Stanford University
Palo Alto, California, 94305
Washington University
St Louis, Missouri, 63126
About this study
Official title: Type 1 Diabetes and the Brain in Children: Metabolic Interventions. Protocol #1: Longitudinal Assessment
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Observational
- Keywords
- Brain Growth and Development, Cognition, Children, Continuous Glucose Monitoring, MRI, Functional MRI
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationalOther
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 years
Changes in Neurocognitive metrics including IQ as well as executive and visual-spatial memory.
We will perform neurocognitive metrics reflecting frontal, parietal-occipital and hippocampal function. Children with T1D will be followed longitudinally and compared with controls to determine whether these differences are associated with measures of glycemic control.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2015 (estimated)
- Study startMar 2015
- Primary completionNov 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University, Washington University School of Medicine, Yale University, University of Iowa
- Responsible party
- Principal investigator, Nelly Mauras, Nemours Children's Clinic
- Investigators
- Nelly Mauras, MD, Principal investigator, Nemours Children's ClinicAllan L Reiss, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02351466
- Sponsor's protocol ID
- 588973
- Status last verified
- Oct 2020
- First submitted
- 27 Jan 2015
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25488901Cato 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.
PubMed 24512675Barnea-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.
PubMed 24319123Marzelli 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.
PubMed 24170697Barnea-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.
PubMed 24096802Tansey 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.
PubMed 25496062Mauras 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.
PubMed 33568403
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Type 1 Diabetes and the Brain in Children: Metabolic Interventions. Protocol #1: Longitudinal Assessment
- ClinicalTrials.gov ID
- NCT02351466
- Acronym / sponsor ID
- 588973
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Brain Growth and Development, Cognition, Children, Continuous Glucose Monitoring, MRI, Functional MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Collaborators
- Stanford University, Washington University School of Medicine, Yale University, University of Iowa
- Study start
- Mar 2015
- Primary completion
- Nov 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 30 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Children with Type 1 Diabetes | – | Other: ObservationalSubjects 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. |
| Healthy Controls | – | Other: ObservationalSubjects will undergo a physical exam and blood test as well as structural and functional brain MRI at baseline and after 24 months. |
Who may qualify
- Ages
- 7 to 16 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Children with Type 1 Diabetes or Healthy non-diabetic controls
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Observational | Other | Children with Type 1 Diabetes, Healthy Controls |
Primary outcome
Changes in total and regional gray and white matter volumes and white matter microstructure.
Time frame: 2 years
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 secondary outcomes
Measures of activation of frontal-parietal networks and functional connectivity of resting state networks using blood oxygen level dependent (BOLD)-functional MRI.
Time frame: 2 years
Changes in Neurocognitive metrics including IQ as well as executive and visual-spatial memory.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Background: PubMed 25488901Mauras 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.
- Background: PubMed 24512675Cato 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.
- Background: PubMed 24319123Barnea-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.
- Background: PubMed 24170697Marzelli 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.
- Background: PubMed 24096802Barnea-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.
- Background: PubMed 25496062Tansey 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.
- Derived from this study: PubMed 33568403Mauras 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nelly Mauras, MD principal investigator
Nemours Children's Clinic
Allan L Reiss, MD principal investigator
Stanford University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 1, run by Nemours Children's Clinic at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in total and regional gray and white matter volumes and white matter microstructure. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02351466, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.