JCHR

Current DirecNet Studies

A Randomized Clinical Trial to Assess the Efficacy and Safety of Real-Time Continuous Glucose Monitoring in the Management of Type 1 Diabetes in Young Children (4 to <10 Year Olds)

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 Subjects with T1D who are 4.0 to <10.0 years old will be enrolled into the multi-center protocol which consists of two phases:

1. A 6-month randomized trial comparing a CGM group with a control group that will use home glucose meter (HGM) monitoring and have the same number of scheduled phone contacts and visits as the CGM group, followed by:
2. A 6-month period during which the CGM Group continues to use CGM and CGM is initiated in the control group. This 2nd phase of the study will evaluate whether any beneficial effect seen in the first 6 months can be sustained with longer-term use and less intensive contact. As the control group will initiate CGM use with less intensive contact after the first month than was provided at initiation of CGM use in the CGM group in phase 1, this will also allow us to assess if beneficial effects of CGM use can be obtained with more practical personnel intervention.

1. Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least twelve months
2. Age >4.0 to <10.0 years
3. HbA1c >7.0% (measured with DCA2000 or other local point-of-care device)
4. Current insulin regimen involves either use of an insulin pump or multiple daily injections of insulin (at least 3 shots per day) for the last three months, with no plans to switch the modality of insulin administration during the next 6 months.
5. Not been diagnosed prior to 6 months of age
6. Not be taking a medication or have another disease that the investigator feels would prevent him or her from completing any aspect of the study.
7. Not used a CGM at home in the last 6 months
8. Not participating in an intervention study in the last 6 weeks
9. No expectation that subject will be moving out of the area of the clinical center during the next 12 months, unless the move will be to an area served by another study center.

Study Procedures
On the day of enrollment, a hemoglobin A1c level will be obtained, and potential subjects will be evaluated for study eligibility through the elicitation of a medical history and performance of a physical examination by a study investigator.

The subject will return for a second visit about 6 weeks after the enrollment visit. At this visit, quality of life questionnaires will be completed and a CGM sensor will be inserted. The monitor will be blinded so that the glucose values cannot be seen. The parent will be instructed on insertion, calibration, and care of the CGM.

The subject will return for a randomization visit 14 to 28 days after the blinded CGM was initiated.

• Subjects who have been compliant with use of the CGM and HGM will be randomized to one of two treatment groups: CGM Group or Control Group
• For the CGM Group, the CGM, HGM, and pump data (if applicable) will be reviewed and changes will be made to diabetes management as needed. Parents will be taught to use the protocol-developed instructions for changes to diabetes management to be used in real time based on CGM and HGM data. Instructions for downloading the CGM and HGM will be provided to subjects with a home computer.
• For the Control Group, a HGM and test strips will be provided. The HGM and pump data (if applicable) will be reviewed and changes will be made in diabetes management as needed. The blinded CGM data will be downloaded but will not be reviewed by study personnel until the end of the first 6 months of the study. Parents will be taught to use the protocol-developed instructions for how to make changes to diabetes management based on HGM data.

Both groups will have follow-up visits at 1,4,8,13,19, and 26 weeks (+/- 1 week) plus one contact between each visit (including one phone contact between the second visit and the one week visit) to review their diabetes management.

• Both groups will download device data on a weekly basis (if the subject has a computer). Subjects with email access will be instructed to email the downloaded data to the clinical center prior to each phone contact.
• For both groups, at each visit, the HGM and pump (if applicable) will be downloaded and for the CGM group, the CGM will be downloaded.

In the 13th and 26th weeks, the Control Group will use a blinded CGM for one week. The CGM Group will continue to use the blinded CGM. The Control Group will return the blinded CGM to the clinic after a week. The data will be reviewed by personnel who are not involved in the care of the subject to determine if additional blinded sensor data are needed. The blinded data will not be reviewed by the study personnel for management decisions until the end of the first 6 months of the study.

Following the 26-week visit:

• Subjects in the RT-CGM Group will continue to use the CGM.
• Subjects in the Control Group will be provided with a CGM and sensors after the week of blinded use and will have visits after 1 week and 4 weeks, with a phone contact during the first and second weeks.
• Both groups will have visits after 13 weeks and 26 weeks

Effect of Metabolic Control at Onset of Diabetes on Progression of Type 1 Diabetes

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The purpose of this study is to test the impact of intensive metabolic control from the onset of diabetes on preservation of C-peptide secretion. This study will also test the feasibility and acceptance of this therapy so that it could be considered in future immune intervention studies. The therapy consists of a short course of sub-cutaneous closed-loop diabetic control at the onset of diabetes followed by real-time continuous glucose monitoring (CGM) with use of an insulin pump. 

Following completion of the baseline procedures, participants are randomized to either the Intensive Treatment Group which includes a hospital admission for up to 4-6 days for inpatient closed loop therapy followed by outpatient use of an insulin pump and CGM or the Standard Treatment Group.

To take part in the study, T1DM subjects will need to have:

1. Age 10.0 to <46.0 years.
2. Diagnosis of type 1 diabetes with initiation of insulin therapy within past 7 days (day 1 being the first day of insulin therapy)
3. If participant is female with reproductive potential, willing to avoid pregnancy and pregnancy test negative.
4. Willing to accept randomization to either the intensive diabetes management group or the standard care group.
5. Willing to complete the planned 2 years of follow-up.
6. Able to electronically transmit data monthly.
7. Investigator believes that the participant (and parent/guardian for children) understands and agrees to comply with the study protocol and is capable of undertaking all necessary testing.
8. Not be currently pregnant or lactating, or anticipate getting pregnant in the next one year.
9. Not be currently anemic.
10. Not be taking a medication or have another disease that the investigator feels would prevent him or her from completing any aspect of the study.
11. Not have received inpatient psychiatric treatment in the past 6 months.
12. Not currently participating in another type 1 diabetes treatment study, including an intervention trial for treatment of diabetic ketoacidosis.

Study Procedures
On the day of enrollment, a hemoglobin A1c and autoantibodies samples will be obtained. An abbreviated Mixed Meal Tolerance Test will be administered and potential subjects will be evaluated for study eligibility through the elicitation of a medical history and performance of a physical examination by a study investigator.

Study subjects will be consented and randomized at the clinical sites as soon as possible after diagnosis of diabetes. The goal is to have randomization occur within 48 hours of diagnosis of diabetes; however, enrollment up to seven days after initiation of insulin therapy will be acceptable. Subjects admitted for treatment of DKA with IV insulin and fluids will be asked to consent to the study and will be randomized before their first meal. Subjects who were diagnosed as an outpatient and did not necessarily require hospital admission will come to the CRC for a morning admission for a mixed meal tolerance test, and will be randomized at the time of that admission.

Subjects will be randomly assigned to one of two treatment groups:

 If assigned to Standard Treatment, the subject will:

• Start insulin therapy (this may take place at the clinical site or hospital, depending on the physician's recommendation).
• At home, check blood sugars 4 or more times a day using a blood glucose meter.
• Wear a blinded CGM for 3 days following visits every 3 months for the first 2 years and every 6 months during the last 2 years if they are continuing to produce insulin. 

• Stay in the hospital for 4 to 6 days, during which an insulin pump, continuous glucose monitor, and computer to control glucose levels will be used.
• Keep using an insulin pump and continuous glucose monitor at home for two years.
• At home, check blood sugars 4 or more times a day using a blood glucose meter.

 All participants will be seen for follow-up visits at 2 weeks, 6 weeks, 3 months and then every 3 months for 2 years. If at the end of two years the participant is continuing to produce insulin, he or she will be asked to return for additional visits every 6 months for an additional 2 years.

The following procedures will be completed at each follow-up visit:

• History, including recording of medications and adverse events
• Physical exam (full exam at annual visits and limited/directed exam at other visits)
• Urine pregnancy test (for females with reproductive potential) at the 12-month visit and anytime a period is missed
• Blood sample for local HbA1c assessment at all visits except 2 weeks
• Blood sample for central laboratory HbA1c assessment at all visits beginning with the 3-month visit (except the visits at 15 and 21 months)
• Blood samples for autoantibodies, PBMC, RNA and extra plasma and serum to be stored for possible future analyses
• Mixed Meal Tolerance Test (except the visits at 15 and 21 months)
• Download study devices

• To characterize the neuroanatomical differences in very young children with T1DM and to prospectively determine the changes that occur over the course of two years in comparison with (1) results obtained from a demographically similar group of control children without diabetes, preferably siblings, and (2) publicly available normative data for the various measures.
• To correlate these neuroanatomical changes with the level of hypo- and hyperglycemia exposure as measured with continuous glucose sensors as well as level of glycemia as measured by HbA1c.
• To correlate these neuroanatomical findings with targeted measures of neuropsychological function at baseline and over 18 months in very young children with T1DM and controls.

1. Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least one month
2. Age 4.0 to <8.0 years
3. Positive antibody testing if onset of T1D < 1 year of age (At least one of GAD65, ICA512 or mIAA must be positive)
4. Full-term birth (>34 weeks without complications)
5. Parent/guardian understands the study protocol and agrees to comply with it
6. Subject and primary care giver (i.e., parent or guardian if subject is a minor) comprehend written English (This requirement is due to the fact that some of the neuropsychological tests are only available in English)
7. No expectation that subject will be moving out of the area of the clinical center during the next 18 months, unless the move will be to an area served by another study center.
8. Willingness to use a blinded CGM at 3-month intervals or already using a CGM on a regular basis
9. Informed Consent Form signed by the parent/guardian, with subjects signing the Child Assent Form when required by the local IRB.

1. Age 4.0 years to less than 8.0 years
2. Full-term birth (>34 weeks without complications)
3. Parent/guardian understands the study protocol and agrees to comply with it
4. Primary care giver (i.e., parent or guardian) comprehends written English
5. No expectation that subject/family will be moving out of the area of the clinical center during the next 18 months
6. HbA1c <6.0% as measured by a DCA2000 or other local point of care device
7. Fasting glucose <110 mg/dL as measured by a HGM
8. For relatives of an individual with T1D, negative antibody testing within the last year (GAD65, ICA512, mIAA)
9. Subjects who have not had a negative test in the last year will have a sample drawn to send to a central laboratory for testing

• At baseline and at 18 months: HbA1c, brain MRI and cognitive testing
• At baseline and every 3 months: HbA1c and blinded CGM used for one week to assess glucose levels

• At baseline and at 18 months: HbA1c, brain MRI and cognitive testing