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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04335513
Recruitment Status : Not yet recruiting
First Posted : April 6, 2020
Last Update Posted : April 27, 2020
Sponsor:
Collaborator:
The Leona M. and Harry B. Helmsley Charitable Trust
Information provided by (Responsible Party):
University of Colorado, Denver

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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Prediabetic State Dysglycemia Autoimmune Diabetes Other: Early CGM-guided education and initiation of insulin therapy. Other: Usual care: glucometer surveillance and basic education. Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trial of Early Initiation of CGM-Guided Insulin Therapy in Stage 2 T1D
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention
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.
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.

Active Comparator: Control
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.
  • 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 Measures :
  1. Change in Diabetes Knowledge from baseline to 6 month follow-up. [ Time Frame: Baseline, 6 months ]
    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

  2. Continuous glucose monitor (CGM) % time >140 mg/dL [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    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 :
  1. Change in HbA1c [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    HbA1c from baseline to 52 weeks, adjusted for baseline

  2. % with HbA1c <7.0% [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Percentage of individuals in each group with HbA1c <7.0%

  3. Continuous glucose monitor (CGM) % time in range 60-140 mg/dL [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Data obtained for Dexcom G6 wear with at least 5 days of data.

  4. Continuous glucose monitor (CGM) mean sensor glucose level (mg/dL) [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Data obtained for Dexcom G6 wear with at least 5 days of data.

  5. Continuous glucose monitor (CGM) standard deviation sensor glucose level (mg/dL) [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Data obtained for Dexcom G6 wear with at least 5 days of data.

  6. Continuous glucose monitor (CGM) coefficient of variation sensor glucose level (mg/dL) [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Data obtained for Dexcom G6 wear with at least 5 days of data.

  7. Change in Pediatric Quality of Life Inventory (PedsQL 4.0) score over time [ Time Frame: Baseline and 3, 6, 9 and 12 months ]

    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.


  8. Change in C-peptide response to Oral Glucose Tolerance Test (OGTT) [ Time Frame: Baseline, 6 months, 12 months ]
    C-peptide measurement during standard OGTT, Area under the curve (AUC)

  9. Change in insulin response to Oral Glucose Tolerance Test (OGTT) [ Time Frame: Baseline, 6 months, 12 months ]
    insulin measurement during standard OGTT, Area under the curve (AUC)

  10. Diabetes attitude survey change over time [ Time Frame: Baseline, 6 months, 12 months ]
    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.


Other Outcome Measures:
  1. Activity Monitoring daily steps [ Time Frame: Monthly for months 0, 1, 2, 3, 4, 5, and 6 of study ]
    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).

  2. Parental anxiety regarding diabetes risk [ Time Frame: Baseline, 6 and 12 months ]
    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.

  3. Parental depression symptoms. [ Time Frame: Baseline, 6 and 12 months ]
    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.

  4. Parental perception of ability to impact diabetes risk. [ Time Frame: Baseline, 6 and 12 months ]
    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

  5. Accuracy of parental risk perception. [ Time Frame: Baseline, 6 and 12 months ]
    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).

  6. Parental worry regarding diabetes risk. [ Time Frame: Baseline, 6 and 12 months ]
    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.

  7. Change in height over time [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Change in z-score of height, using CDC (Centers for Disease Control) standards for gender and age.

  8. Change in weight over time [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Change in z-score of weight, using CDC standards for gender and age.

  9. Change in BMI over time [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Change in z-score of BMI using CDC standards for gender and age.

  10. Change in body fat over time [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Change in body fat percentile using Tanita bioelectrical impedance scale

  11. Presence of one or more islet cell autoantibodies:over time [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    islet autoantibodies measured in the blood: GAD65 autoantibody (GADA), islet antigen 2 autoantibody (IA-2A), insulin autoantibody (IAA), and zinc transporter 8 autoantibody (ZnT8A)

  12. Change in glucose tolerance over time by Oral Glucose Tolerance Test (OGTT) [ Time Frame: Baseline, 6 months, 12 months ]

    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),


  13. Continuous glucose monitor (CGM) % time <60 mg/dL [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    Data obtained for Dexcom G6 wear with at least 5 days of data.

  14. areal bone mineral density of the spine measured by osteodensitometry (DXA) [ Time Frame: 3 and 9 month visits ]
    Measured in g/cm2 by Dual-energy X-ray absorptiometry (DXA)

  15. areal bone mineral density of the proximal femur measured by osteodensitometry (DXA) [ Time Frame: 3 and 9 month visits ]
    Measured in g/cm2 by Dual-energy X-ray absorptiometry (DXA)

  16. Change in glycemic control over time [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    1,5 anhydroglucitol

  17. Insulin requirements [ Time Frame: Baseline and 3, 6, 9 and 12 months ]
    total, basal and bolus insulin dose (Units/kg/day), both arms

  18. Severe hypoglycemic episodes [ Time Frame: 12 months ]
    frequency of severe hypoglycemic episodes (BG < 54 mg/dL)

  19. diabetic ketoacidosis (DKA) episodes [ Time Frame: 12 months ]
    frequency of DKA

  20. ER visits and hospitalizations related to glycemia [ Time Frame: 12 months ]
    frequency of ER/Hospitalizations

  21. Adverse events [ Time Frame: 12 months ]
    number, nature and severity of other adverse events

  22. Assessment of frequency of use of CGM (continuous glucose monitor) system [ Time Frame: 12 months ]
    Number of days using CGM

  23. Change in Diabetes Knowledge from 6 month to 12 months follow-up. [ Time Frame: 6 months to 12 months 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. Durability of knowledge from 6-month follow-up to 12 month follow-up will be compared between groups



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04335513


Contacts
Layout table for location contacts
Contact: Brigitte Frohnert, MD, PhD 303.724.6744 brigitte.frohnert@cuanschutz.edu
Contact: Flor Sepulveda, BS 303.724.0328 flor.sepulveda@cuanschutz.edu

Sponsors and Collaborators
University of Colorado, Denver
The Leona M. and Harry B. Helmsley Charitable Trust
Investigators
Layout table for investigator information
Principal Investigator: Brigitte I Frohnert, MD, PhD Barbara Davis Center for Diabetes, University of Colorado
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT04335513    
Other Study ID Numbers: 19-1767
First Posted: April 6, 2020    Key Record Dates
Last Update Posted: April 27, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
Islet autoimmunity
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs