Clinical trial NCT04335513: Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D
Official title: Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type 1 Diabetes
Prediabetic State
Dysglycemia
Autoimmune Diabetes
Keywords: Islet autoimmunity
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: The Leona M. and Harry B. Helmsley Charitable Trust
First posted: 2020-04-06
Enrollment: 84
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 1. 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.
2. 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
3. Evidence of dysglycemia (Stage 2 T1D) using any one of the following criteria:

I. Americal Diabetes Association (ADA) criteria:

1. fasting plasma glucose 100-125 mg/dL
2. OR 2-hour OGTT plasma glucose of 140-199 mg/dL
3. OR A1c 5.7-6.4%
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:

1. ≥15% of values above 140 mg/dL
2. OR peaks ≥ 200 mg/dL on ≥2 days
3. OR average sensor glucose ≥120 mg/dL

IV. Dysglycemia on finger stick blood glucose:

1. Fasting BG above 110 mg/dL on 2 or more days
2. OR 2 hour post-meal BG above 150 mg/dL on ≥ 2 days
3. OR single random BG \> 200 mg/dL

Primary outcomes:
measure: Change in Diabetes Knowledge from baseline to 6 month follow-up.
timeFrame: Baseline, 6 months
measure: Continuous glucose monitor (CGM) % time >140 mg/dL
timeFrame: Baseline and 3, 6, 9 and 12 months
Secondary outcomes:
measure: Change in HbA1c
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: % with HbA1c <7.0%
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Continuous glucose monitor (CGM) % time in range 60-140 mg/dL
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Continuous glucose monitor (CGM) mean sensor glucose level (mg/dL)
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Continuous glucose monitor (CGM) standard deviation sensor glucose level (mg/dL)
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Continuous glucose monitor (CGM) coefficient of variation sensor glucose level (mg/dL)
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Change in Pediatric Quality of Life Inventory (PedsQL 4.0) score over time
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Change in C-peptide response to Oral Glucose Tolerance Test (OGTT)
timeFrame: Baseline, 6 months, 12 months
measure: Change in insulin response to Oral Glucose Tolerance Test (OGTT)
timeFrame: Baseline, 6 months, 12 months
measure: Diabetes attitude survey change over time
timeFrame: Baseline, 6 months, 12 months
Other outcomes:
measure: Activity Monitoring daily steps
timeFrame: Monthly for months 0, 1, 2, 3, 4, 5, and 6 of study
measure: Parental anxiety regarding diabetes risk
timeFrame: Baseline, 6 and 12 months
measure: Parental depression symptoms.
timeFrame: Baseline, 6 and 12 months
measure: Parental perception of ability to impact diabetes risk.
timeFrame: Baseline, 6 and 12 months
measure: Accuracy of parental risk perception.
timeFrame: Baseline, 6 and 12 months
measure: Parental worry regarding diabetes risk.
timeFrame: Baseline, 6 and 12 months
measure: Change in height over time
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Change in weight over time
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Change in BMI over time
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Change in body fat over time
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Presence of one or more islet cell autoantibodies:over time
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Change in glucose tolerance over time by Oral Glucose Tolerance Test (OGTT)
timeFrame: Baseline, 6 months, 12 months
measure: Continuous glucose monitor (CGM) % time <60 mg/dL
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: areal bone mineral density of the spine measured by osteodensitometry (DXA)
timeFrame: 3 and 9 month visits
measure: areal bone mineral density of the proximal femur measured by osteodensitometry (DXA)
timeFrame: 3 and 9 month visits
measure: Change in glycemic control over time
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Insulin requirements
timeFrame: Baseline and 3, 6, 9 and 12 months
measure: Severe hypoglycemic episodes
timeFrame: 12 months
measure: diabetic ketoacidosis (DKA) episodes
timeFrame: 12 months
measure: ER visits and hospitalizations related to glycemia
timeFrame: 12 months
measure: Adverse events
timeFrame: 12 months
measure: Assessment of frequency of use of CGM (continuous glucose monitor) system
timeFrame: 12 months
measure: Change in Diabetes Knowledge from 6 month to 12 months follow-up.
timeFrame: 6 months to 12 months follow-up
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center
state: Colorado
Study officials:
affiliation: Barbara Davis Center for Diabetes, University of Colorado
name: Brigitte I Frohnert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: