Back to resultsTrial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D (TESS)
Primary Purpose
Type 1 Diabetes, Prediabetic State, Dysglycemia
Status
Enrolling by invitation
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Early CGM-guided education and initiation of insulin therapy.
Usual care: glucometer surveillance and basic education.
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Islet autoimmunity
Eligibility Criteria
- 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
Sites / Locations
- Barbara Davis Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Intervention
Control
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
Change in HbA1c
HbA1c from baseline to 52 weeks, adjusted for baseline
% with HbA1c <7.0%
Percentage of individuals in each group with HbA1c <7.0%
Continuous glucose monitor (CGM) % time in range 60-140 mg/dL
Data obtained for Dexcom G6 wear with at least 5 days of data.
Continuous glucose monitor (CGM) mean sensor glucose level (mg/dL)
Data obtained for Dexcom G6 wear with at least 5 days of data.
Continuous glucose monitor (CGM) standard deviation sensor glucose level (mg/dL)
Data obtained for Dexcom G6 wear with at least 5 days of data.
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.
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.
Change in C-peptide response to Oral Glucose Tolerance Test (OGTT)
C-peptide measurement during standard OGTT, Area under the curve (AUC)
Change in insulin response to Oral Glucose Tolerance Test (OGTT)
insulin measurement during standard OGTT, Area under the curve (AUC)
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.
Full Information
NCT ID
NCT04335513
First Posted
March 17, 2020
Last Updated
May 6, 2022
Sponsor
University of Colorado, Denver
Collaborators
The Leona M. and Harry B. Helmsley Charitable Trust
1. Study Identification
Unique Protocol Identification Number
NCT04335513
Brief Title
Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D
Acronym
TESS
Official Title
Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Enrolling by invitation
Study Start Date
April 30, 2020 (Actual)
Primary Completion Date
July 31, 2023 (Anticipated)
Study Completion Date
July 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
The Leona M. and Harry B. Helmsley Charitable Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, Prediabetic State, Dysglycemia, Autoimmune Diabetes
Keywords
Islet autoimmunity
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Early CGM-guided education and initiation of insulin therapy.
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Usual care: glucometer surveillance and basic education.
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Diabetes Knowledge from baseline to 6 month follow-up.
Description
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
Time Frame
Baseline, 6 months
Title
Continuous glucose monitor (CGM) % time >140 mg/dL
Description
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.
Time Frame
Baseline and 3, 6, 9 and 12 months
Secondary Outcome Measure Information:
Title
Change in HbA1c
Description
HbA1c from baseline to 52 weeks, adjusted for baseline
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
% with HbA1c <7.0%
Description
Percentage of individuals in each group with HbA1c <7.0%
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Continuous glucose monitor (CGM) % time in range 60-140 mg/dL
Description
Data obtained for Dexcom G6 wear with at least 5 days of data.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Continuous glucose monitor (CGM) mean sensor glucose level (mg/dL)
Description
Data obtained for Dexcom G6 wear with at least 5 days of data.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Continuous glucose monitor (CGM) standard deviation sensor glucose level (mg/dL)
Description
Data obtained for Dexcom G6 wear with at least 5 days of data.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Continuous glucose monitor (CGM) coefficient of variation sensor glucose level (mg/dL)
Description
Data obtained for Dexcom G6 wear with at least 5 days of data.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Change in Pediatric Quality of Life Inventory (PedsQL 4.0) score over time
Description
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.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Change in C-peptide response to Oral Glucose Tolerance Test (OGTT)
Description
C-peptide measurement during standard OGTT, Area under the curve (AUC)
Time Frame
Baseline, 6 months, 12 months
Title
Change in insulin response to Oral Glucose Tolerance Test (OGTT)
Description
insulin measurement during standard OGTT, Area under the curve (AUC)
Time Frame
Baseline, 6 months, 12 months
Title
Diabetes attitude survey change over time
Description
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.
Time Frame
Baseline, 6 months, 12 months
Other Pre-specified Outcome Measures:
Title
Activity Monitoring daily steps
Description
Activity tracker average of steps per day from at least 5 days of data at each time point. Average daily steps will be analyzed using linear mixed models incorporating data from all seven 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 interest (intervention vs controls).
Time Frame
Monthly for months 0, 1, 2, 3, 4, 5, and 6 of study
Title
Parental anxiety regarding diabetes risk
Description
Items from a questionnaire to study the psychological impact of diabetes risk. A 6-item short form of the state portion of the State-Trait Anxiety Inventory (STAI) will be used to assess parent anxiety about the child's diabetes risk at a single point in time. For example, parents were asked how often they feel "worried" specifically when they think about their child's risk of developing diabetes. Responses were scored on a 4-point scale and the 6-item score was then converted to a total score comparable to the 20-item State Anxiety Inventory score. Parents with STAI scores > 40 were considered to be highly anxious. STAI scores will be analyzed using linear mixed models incorporating data from all three 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.
Time Frame
Baseline, 6 and 12 months
Title
Parental depression symptoms.
Description
Items from a questionnaire to study the psychological impact of diabetes risk. A 6-item set of questions quering frequency of depressive symptoms will be used to assess parent depressive symptoms at a single point in time. For example, parents will be asked about frequency of crying spells on a 4 point scale from (1) Not at all to (4) All of the time. Responses are scored from 6 to 24, with higher score indicating increased depressive symptoms.
Time Frame
Baseline, 6 and 12 months
Title
Parental perception of ability to impact diabetes risk.
Description
Items from a questionnaire to study the psychological impact of diabetes risk. A 3 item survey, each item answered on a likert scale from 1-5: (1) strongly agree to (5) strongly disagree. Risk modification belief scoring is scored on 3-15 points with higher score indicating perception that risk of diabetes can be modified. Risk modification scores will be analyzed using linear mixed models incorporating data from all three 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 control
Time Frame
Baseline, 6 and 12 months
Title
Accuracy of parental risk perception.
Description
Items from a questionnaire to study the psychological impact of diabetes risk. The accuracy of parental perception of the child's risk for developing type 1 diabetes (T1D) is scored as accurate or inaccurate on a questionnaire (accurate: indicating the child's T1D risk was higher or much higher than other children's T1D risk; inaccurate: indicating the child's T1D risk was the same, somewhat lower or much lower than other children's T1D risk).
Time Frame
Baseline, 6 and 12 months
Title
Parental worry regarding diabetes risk.
Description
Item from a questionnaire to study the psychological impact of diabetes risk. The frequency of worry regarding whether the child will develop diabetes is scored on a five item scale from (1) Never to (5) Very often. A score of 5 indicates increased level of worry.
Time Frame
Baseline, 6 and 12 months
Title
Change in height over time
Description
Change in z-score of height, using CDC (Centers for Disease Control) standards for gender and age.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Change in weight over time
Description
Change in z-score of weight, using CDC standards for gender and age.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Change in BMI over time
Description
Change in z-score of BMI using CDC standards for gender and age.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Change in body fat over time
Description
Change in body fat percentile using Tanita bioelectrical impedance scale
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Presence of one or more islet cell autoantibodies:over time
Description
islet autoantibodies measured in the blood: GAD65 autoantibody (GADA), islet antigen 2 autoantibody (IA-2A), insulin autoantibody (IAA), and zinc transporter 8 autoantibody (ZnT8A)
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Change in glucose tolerance over time by Oral Glucose Tolerance Test (OGTT)
Description
Abnormal glucose tolerance is defined as:
Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L) and < 126 mg/dL (7 mmol/L), or 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L) and < 200 (11.1 mmol/L), or 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)
OGTT values diagnostic of diabetes is defined as:
Fasting plasma glucose >126 mg/dL (7 mmol/L), or 2 hour plasma glucose >200 (11.1 mmol/L),
Time Frame
Baseline, 6 months, 12 months
Title
Continuous glucose monitor (CGM) % time <60 mg/dL
Description
Data obtained for Dexcom G6 wear with at least 5 days of data.
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
areal bone mineral density of the spine measured by osteodensitometry (DXA)
Description
Measured in g/cm2 by Dual-energy X-ray absorptiometry (DXA)
Time Frame
3 and 9 month visits
Title
areal bone mineral density of the proximal femur measured by osteodensitometry (DXA)
Description
Measured in g/cm2 by Dual-energy X-ray absorptiometry (DXA)
Time Frame
3 and 9 month visits
Title
Change in glycemic control over time
Description
1,5 anhydroglucitol
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Insulin requirements
Description
total, basal and bolus insulin dose (Units/kg/day), both arms
Time Frame
Baseline and 3, 6, 9 and 12 months
Title
Severe hypoglycemic episodes
Description
frequency of severe hypoglycemic episodes (BG < 54 mg/dL)
Time Frame
12 months
Title
diabetic ketoacidosis (DKA) episodes
Description
frequency of DKA
Time Frame
12 months
Title
ER visits and hospitalizations related to glycemia
Description
frequency of ER/Hospitalizations
Time Frame
12 months
Title
Adverse events
Description
number, nature and severity of other adverse events
Time Frame
12 months
Title
Assessment of frequency of use of CGM (continuous glucose monitor) system
Description
Number of days using CGM
Time Frame
12 months
Title
Change in Diabetes Knowledge from 6 month to 12 months follow-up.
Description
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. Durability of knowledge from 6-month follow-up to 12 month follow-up will be compared between groups
Time Frame
6 months to 12 months follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brigitte I Frohnert, MD, PhD
Organizational Affiliation
Barbara Davis Center for Diabetes, University of Colorado
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Davis Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D
We'll reach out to this number within 24 hrs