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

Study Overview
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Brief Summary
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The purpose of this study is to find out if very tight blood glucose control from the onset of Type 1 Diabetes can preserve beta cell function. Study subjects will be randomly assigned to receive either standard diabetes management or intensive diabetes management, which involves several days of closed loop therapy followed by home use of a continuous glucose monitor and insulin pump.

Detailed Description
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The specific aim of this study is to determine if early restoration of metabolic control will improve C-peptide production compared to children receiving routine diabetes management and the secondary aim is to determine if allowing the islet cells to be less metabolically active will have an impact on the underlying autoimmune process. Following completion of the baseline procedures (Mixed Meal Tolerance Test and blood sample collection), participants are randomized to either the Standard Treatment Group or the Intensive Treatment Group which includes 4-6 days of inpatient closed loop therapy followed by outpatient use of an insulin pump and continuous glucose monitor for diabetes management. All subjects will be seen 7 times in the first year and 4 times in the second year for follow-up testing. Subjects who are still producing insulin after 2 years may be asked to return every 6 months for an additional 2 years.

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

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Closed loop
* Device: Home glucose monitoring
* Device: Insulin pump
* Device: Continuous glucose monitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6.0 to <46.0 years Diagnosis of type 1 diabetes with initiation of insulin therapy within past 7 days (day 1 being the first day of insulin therapy) If participant is female with reproductive potential, willing to avoid pregnancy and pregnancy test negative. Willing to accept randomization to either the intensive diabetes management group or the standard care group. Willing to complete the planned 2 years of follow-up. Able to electronically transmit data monthly. 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. Exclusion Criteria: Currently pregnant or lactating, or anticipate getting pregnant in the next one year. Currently anemic (hematocrit level will be obtained at the screening visit). Chronic use of systemic steroids or other noninsulin pharmaceuticals that might affect glycemic control or the presence of a disease that is likely to be treated with such medications during the first two years of the study. Complicating medical issues that might interfere with study conduct. Inpatient psychiatric treatment in the past 6 months (if the participant is a minor, for either the participant or the participant's primary care giver). Currently participating in another type 1 diabetes treatment study, including an intervention trial for treatment of diabetic ketoacidosis.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive Treatment<br>closed loop therapy (4-6 days), insulin pump (2 years), continuous glucose monitoring (2 years), home glucose monitoring (2 years) | Device: Closed loop<br>* Closed loop therapy for up to 4 to 6 days<br>Device: Home glucose monitoring<br>* Standard diabetes management using a home glucose meter.<br>Device: Insulin pump<br>* Insulin pump use for 2 years<br>Device: Continuous glucose monitor<br>* Continuous glucose monitor use for 2 years<br>|
| Active Comparator: Standard Treatment<br>home glucose monitoring (2 years) | Device: Home glucose monitoring<br>* Standard diabetes management using a home glucose meter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide Average Area Under the Curve (AUC) in Response to a Mixed Meal at 1 Year Following Enrollment. | In the primary analysis of the 12-month Mixed-Meal Tolerance Test (MMTT) results, the geometric mean (95% C.I.) of C-peptide average AUC (=AUC/time) was 0.43 (0.34, 0.52) pmol/ml in the intensive treatment group and 0.52 (0.32, 0.75) pmol/ml in the usual care group (P=0.49). | At baseline, MMTT data were collected at 0 and 90 min; at 12 months, MMTT data were collected at 0 to 240 min post meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak C-peptide in Response to a Mixed Meal at 1 Year Following Enrollment |  | 0 to 240 min post meal at 1 year MMTT | 
| Incidence of the Loss of the 2 Hour Peak C-peptide < 0.2 Pmol/ml on a Semi-annual MMTT | Outcome measure in the table is the incidence of 2 hour peak C-peptide>=0.2 pmol/ml. Since the formal clinical trial stopped at 12 months due to lack of efficiency (later follow-up were used to collect data for secondary analyses by pooling the two groups), only the outcome at 12 months are reported. | 0 to 240 min post meal at 1 year MMTT | 
| HbA1c |  | 1 year | 
| Adverse Events (Severe Hypoglycemia) |  | 1 year | 
| CGM Mean Glucose |  | 1 year | 
| CGM Measured Glucose Outcomes | Include a series of glucose indices created from CGM measured glucose data, such as % time with glucose values <=70 mg/dl, % time with glucose values within target range of 71-180 mg/dl, % time with glucose values >180 mg/dl, and glucose variability as measured by coefficient of variation. These indices were calculated by giving equal weight to each of the 24 h of the day. At least 24 h of CGM data were required for calculating these indices. | 1 year | 
| Daily Insulin Dose |  | 1 year | 
| BMI Percentile |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Closed Loop Therapy, Continuous Glucose Monitor