Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D

Study Overview
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Brief Summary
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This protocol is an intervention study to determine the best education and monitoring strategy for children ages 2-20 years with pre-symptomatic type 1 diabetes (T1D) because there currently exists no clinical guidelines for management of these children in early-stage T1D. This study hypothesizes that the trajectory of T1D can be changed, substantially reducing HbA1c and risk of DKA at diagnosis, through (1) careful monitoring of children progressing from stage 2 to stage 3 T1D using continuous glucose monitor (CGM) technology, (2) staged education targeted to assist families in recognizing evolving dysglycemia, and (3) addressing glycemic abnormalities with early initiation of insulin.

Detailed Description
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Specific Aims: Perform randomized controlled trial of intensive follow-up of stage 2 T1D participants utilizing continuous glucose monitoring (CGM) technology and early education of families to guide early insulin therapy with the goals of: maintaining HbA1c less than 7.0%. avoiding adverse outcomes: ER visits, hospitalizations, DKA and severe hypoglycemia improving diabetes knowledge through optimal planned education as opposed to 'a crash course' at unexpected diagnosis event. evaluating patient/caregiver satisfaction with diabetes care received evaluating impact of activity on glycemic profile Collect longitudinal biomarkers of beta-cell stress and dysfunction in stage 2 T1D. Use longitudinal CGM data combined with gold-standard OGTT and HbA1c measures to provide evidence for CGM-based diagnostic criteria for stage 2 and stage 3 T1D. Perform cost-analysis of intensive follow up protocol.

Official Title
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Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D

Conditions
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Type 1 Diabetes, Prediabetic State, Dysglycemia, Autoimmune Diabetes

Intervention / Treatment
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* Other: Early CGM-guided education and initiation of insulin therapy.
* Other: Usual care: glucometer surveillance and basic education.


Participation Criteria
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Eligibility Criteria
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Individuals identified in stage 2 T1D through ongoing screening studies at the Barbara Davis Center (ASK, DAISY, TrialNet, and TEDDY) who have given permission to be contacted about study opportunities. Presence of islet autoimmunity with high risk of progression: i. positive for multiple islet autoantibodies at 2 or more visits -OR- ii. positive for a single high-affinity islet autoantibody at 2 or more visits Evidence of dysglycemia (Stage 2 T1D) using any one of the following criteria: I. Americal Diabetes Association (ADA) criteria: fasting plasma glucose 100-125 mg/dL OR 2-hour OGTT plasma glucose of 140-199 mg/dL OR A1c 5.7-6.4% OR ≥10% increase in A1c from previous visit II. Dysglycemia on OGTT (TrialNet Criteria): a. glucose above 200 mg/dL on 30, 60 OR 90 minute values III. Dysglycemia on CGM worn for at least 5 days: ≥15% of values above 140 mg/dL OR peaks ≥ 200 mg/dL on ≥2 days OR average sensor glucose ≥120 mg/dL IV. Dysglycemia on finger stick blood glucose: Fasting BG above 110 mg/dL on 2 or more days OR 2 hour post-meal BG above 150 mg/dL on ≥ 2 days OR single random BG > 200 mg/dL

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Intervention<br>Early diabetes management and education including focused education based on pathophysiology of type 1 diabetes, factors which impact blood glucose, and effects of insulin using data from continuous glucose monitoring device (CGM) worn unblinded at least 20 days per month with interpretation and education on results. Early initiation of insulin therapy, when warranted based on a pattern of prolonged or repeated high blood glucose values. | Other: Early CGM-guided education and initiation of insulin therapy.<br>* Careful monitoring of children progressing from stage 2 to stage 3 T1D using continuous glucose monitor (CGM) technology, staged education targeted to assist families in recognizing evolving dysglycemia, and addressing glycemic abnormalities with early initiation of insulin can substantially reduce the HbA1c and risk of DKA at diagnosis, thereby changing the trajectory of the disease course.<br>|
| Active Comparator: Control<br>Usual education and advice on glycemic surveillance based on protocols of TEDDY/DAISY/ASK (ongoing studies at BDC). This includes: blood glucose checks 2-3 times per month, participant-led contact with study personnel when abnormalities are noted and transition to clinical care when criteria for clinical type 1 diabetes are met. | Other: Usual care: glucometer surveillance and basic education.<br>* Usual education and advice on glycemic surveillance based on protocols of TEDDY/DAISY/ASK. Blinded CGM for 10 days every 3 months to collect data on glycemic profile with basic feedback regarding changes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Diabetes Knowledge from baseline to 6 month follow-up. | 35-item diabetes questionnaire with possible responses true/false/don't know. Total score is the number of correct answers out of 35, with more correct answers indicating higher knowledge. Change from baseline to 6-month follow-up will be compared between groups | Baseline, 6 months | 
| Continuous glucose monitor (CGM) % time >140 mg/dL | Data obtained for Dexcom G6 wear with at least 5 days of data at each time point. Continuous glucose monitor (CGM) % time >140 mg/dL will be analyzed using linear mixed models incorporating data from all 5 time points, with an interaction between group and time to test for differences in change in outcome over time. Contrast statements will be used to test for comparisons of intervention vs controls. | Baseline and 3, 6, 9 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | HbA1c from baseline to 52 weeks, adjusted for baseline | Baseline and 3, 6, 9 and 12 months | 
| % with HbA1c <7.0% | Percentage of individuals in each group with HbA1c <7.0% | Baseline and 3, 6, 9 and 12 months | 
| Continuous glucose monitor (CGM) % time in range 60-140 mg/dL | Data obtained for Dexcom G6 wear with at least 5 days of data. | Baseline and 3, 6, 9 and 12 months | 
| Continuous glucose monitor (CGM) mean sensor glucose level (mg/dL) | Data obtained for Dexcom G6 wear with at least 5 days of data. | Baseline and 3, 6, 9 and 12 months | 
| Continuous glucose monitor (CGM) standard deviation sensor glucose level (mg/dL) | Data obtained for Dexcom G6 wear with at least 5 days of data. | Baseline and 3, 6, 9 and 12 months | 
| Continuous glucose monitor (CGM) coefficient of variation sensor glucose level (mg/dL) | Data obtained for Dexcom G6 wear with at least 5 days of data. | Baseline and 3, 6, 9 and 12 months | 
| Change in Pediatric Quality of Life Inventory (PedsQL 4.0) score over time | The PedsQL 4.0 measures health-related quality of life across the domains of Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. ThePedsQL has parallel forms for parents of children aged 2-4, 5-7, 8-12, and 13-18 years. The child version has parallel forms for children aged 5-7, 8-12, and 13-18. Responses to items use a 5-point Likert scale (0 = never a problem, 4 = almost always a problem). Items are reverse scored and transformed to a 0 to 100 scale with higher scores indicating better quality of life. | Baseline and 3, 6, 9 and 12 months | 
| Change in C-peptide response to Oral Glucose Tolerance Test (OGTT) | C-peptide measurement during standard OGTT, Area under the curve (AUC) | Baseline, 6 months, 12 months | 
| Change in insulin response to Oral Glucose Tolerance Test (OGTT) | insulin measurement during standard OGTT, Area under the curve (AUC) | Baseline, 6 months, 12 months | 
| Diabetes attitude survey change over time | 10 item survey, each item answered on a likert scale from 1-5: (1) strongly disagree to (5) strongly agree. Scoring is on 4 scales: (1) Value of Tight Control, scored on 4-20 points with higher score indicating agreement with importance of control; (2) Psychosocial Impact, scored on 2-10 points with higher score indicating agreement with high impact of diabetes on psychosocial factors; (3) Patient Autonomy, scored on 2-10 points with higher score indicating agreement with value of autonomy; and (4) Confidence, scored on 2-10 points with higher score indicating confidence in knowledge and skills. | Baseline, 6 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Islet autoimmunity