Type 1 Diabetes Mellitus
Conditions
Keywords
Insulin pump, Closed loop, Brain development, Pediatric, Type 1 Diabetes, MRI, Cognitive development
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.
Interventions
DEVICEClosed Loop (Medtronic 670G)
A loaner Medtronic 670G insulin pump, Enlite 3 sensor and GST3C Guardian transmitter will be utilized
OTHERStandard Care
Subjects will continue on their current treatment (insulin pump or injections), with follow up every 3 months.
Sponsors
National Institutes of Health (NIH)
Washington University School of Medicine
Stanford University
University of Iowa
Yale University
Jaeb Center for Health Research
Nemours Children's Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Gray Matter Volume in the Brain | 6 months | Trends in total and regional grey matter volume |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Brain Activation (Dorsal Anterior Cingulate, Inferior Frontal Gyrus and/or Parietal Cortex) | 6 months | 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) | 6 months | 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. |
Countries
United States
Participant flow
Pre-assignment details
Two enrolled participants did not meet inclusion/exclusion criteria and were screen failures before randomization. Two additional participants failed to complete all required baseline assessments or procedures. The remaining 42 subjects participated in the study and were included in all data analyses in line with the intention to treat principle. There were no additional participant losses.
Participants by arm
| Arm | Count |
|---|---|
| Standard Care 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.
Standard Care: Subjects will continue on their current treatment (insulin pump or injections), with follow up every 3 months. | 21 |
| Closed-Loop 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.
Closed Loop (Medtronic 670G): A loaner Medtronic 670G insulin pump, Enlite 3 sensor and GST3C Guardian transmitter will be utilized | 21 |
| Total | 42 |
Baseline characteristics
| Characteristic | Standard Care | Total | Closed-Loop |
|---|---|---|---|
| Age, Categorical <=18 years | 21 Participants | 42 Participants | 21 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.7 years STANDARD_DEVIATION 0.97 | 15.8 years STANDARD_DEVIATION 1.1 | 15.9 years STANDARD_DEVIATION 1.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 40 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Gray Matter Volume | 739.16 cm^3 | 734.22 cm^3 | 727.27 cm^3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 34 Participants | 15 Participants |
| Region of Enrollment United States | 21 Participants | 42 Participants | 21 Participants |
| Sex: Female, Male Female | 9 Participants | 23 Participants | 14 Participants |
| Sex: Female, Male Male | 12 Participants | 19 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 2 / 21 |
Outcome results
Primary
Changes in Gray Matter Volume in the Brain
Trends in total and regional grey matter volume
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Care | Changes in Gray Matter Volume in the Brain | -4.83 centimeters cubed |
| Closed-Loop | Changes in Gray Matter Volume in the Brain | -9.31 centimeters cubed |
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.
Time frame: 6 months
Population: fMRI was not available for 3 Subjects in the Standard Care Group and for 1 in the Closed-Loop Group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Care | Changes in Brain Activation (Dorsal Anterior Cingulate, Inferior Frontal Gyrus and/or Parietal Cortex) | 78.58 parameter estimates (betas) |
| Closed-Loop | Changes in Brain Activation (Dorsal Anterior Cingulate, Inferior Frontal Gyrus and/or Parietal Cortex) | -119.51 parameter estimates (betas) |
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.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Care | Changes in WASI-II Perceptual Reasoning Index (PRI) | 2.05 score on a scale |
| Closed-Loop | Changes in WASI-II Perceptual Reasoning Index (PRI) | 6.10 score on a scale |