Artificial Pancreas - Adolescent Physiology & Psychology Longitudinal Evaluation
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Type 1 Diabetes
- Sponsor
- University of Virginia
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Randomized substudy: The 24-month HbA1c between AP system and Usual Care+CGM groups, performed as regression, adjusted for baseline HbA1c.
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This study designed to assess changes in control of Type 1 Diabetes in pubertal adolescents over a two year period. There are two arms/substudies, the first being a longitudinal randomized controlled trial and the second an observational study.
Detailed Description
The investigators will recruit adolescents with type 1 diabetes age 11-\<13 years and one parent to participate in this 24-month study. While this is admittedly a long enrollment time, study commitments following enrollment will be limited to three in-person or video visits at yearly intervals and one virtual or in-person device training session to improve adherence. Participants must be pubertal, as puberty appears to contribute significantly to the insulin resistance that is likely related to worsened blood glucose control. Pubertal assessments will occur at yearly intervals. The first of the two arms/substudies ("Randomized" substudy) is a longitudinal randomized controlled trial for which participants will be randomized to either continue their current diabetes therapy (with the addition of use of a Dexcom CGM, forming the "Usual Care+CGM" Control Group; this includes both adolescents using non-automated insulin delivery (AID) insulin pumps or multiple daily injections \[MDI\]). The Experimental Group will use an AP system (Tandem's Control-IQ system) during the two-year duration of the study. The primary outcome of the Randomized substudy will be HbA1c between intervention groups at the 24-month visit. The second arm/substudy ("Triple Label Surveillance" substudy) is an observational study. Both arms/substudies perform a "Triple Label" mixed meal study assessing glucose flux and insulin resistance that requires visits to the Clinical Research Unit. All participants will undergo a Triple-Labeled Glucose Assessment at months 0, 12 and 24. This assessment evaluates the degree of insulin resistance including in the hepatic and peripheral compartments. During Visit 2, all participants (for both the Triple Label sub-study and the Glycemia-Only sub-study) will complete multiple questionnaires assessing aspects of adolescent psychology and sociology. HbA1c will also be collected using a local lab. The primary outcome of the study overall (combined Triple Label Surveillance and Randomized substudies) is the change in insulin resistance between baseline and the 24-month visit. CGM glucose data will be collected continuously via remote connection during the entire study. At months 6 and 18, participants will be contacted to obtain insulin management information and will have HbA1c measures assessed at a local clinic or laboratory. Additional scheduled phone calls will occur in the month before the in-person study visits to request HbA1c and confirm body composition/Triple-Labeled Glucose Assessment scheduling and discuss use of CGM and activity tracker. Participants will be contacted in the event of insufficient CGM or AP system use. For the Randomized substudy, in the Eperimental Group, insufficient use is defined as \<60% AP use over a 3-month period. For the Control Group, less than 1 month of CGM data over a 3-month period is considered insufficient. If participants do not meet minimum use criteria in 2 successive periods, the participant will be discontinued from the study. The investigators are targeting completion of 42 child/parent dyads combined between the Randomized substudy and the Triple Label Surveillance sub-study.
Investigators
Mark D. DeBoer, MD, MSc., MCR
Professor
University of Virginia
Eligibility Criteria
Inclusion Criteria
- •Age 11 to \<13 years (at time of enrollment) with a parent/guardian (18+ yo) who is willing to participate with the child
- •At least Tanner 2 pubic hair (boys), Tanner 2 breast development (girls)
- •HbA1c \<10 clinically obtained within the last 6 weeks; if the participant is unable to go to the laboratory or clinic because of stay-at-home orders, the entry hemoglobin A1c level can be assessed via outside laboratory (e.g. LabCorp), home HbA1c device, recent clinically-obtained HbA1c in past month..
- •Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year
- •Currently using insulin for at least six months
- •Both prior pump and MDI users will use insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections
- •Access to internet and willingness to upload data during the study as needed
- •For females, not currently known to be pregnant or breastfeeding
- •If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of childbearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
- •Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use
Exclusion Criteria
- •Hemoglobin A1c \>10% clinically obtained within the past 6 weeks
- •A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:
- •Severe renal impairment, end-stage renal disease, or dialysis
- •Inpatient psychiatric treatment in the past six months
- •Presence of a known adrenal disorder
- •Abnormal liver function test results (Transaminase\>2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function
- •Uncontrolled thyroid disease
- •Concurrent use of any non-insulin glucose-lowering agent.
- •Hemophilia or any other bleeding disorder.
- •History of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment
Outcomes
Primary Outcomes
Randomized substudy: The 24-month HbA1c between AP system and Usual Care+CGM groups, performed as regression, adjusted for baseline HbA1c.
Time Frame: 2 years
Measure of HbA1c
Combined Triple Label Surveillance and Randomized substudies: Change in insulin sensitivity (Si) over time
Time Frame: Baseline, 12 months, 24 months
Changes in Si (from triple-label, mixed-meal test) over time between baseline and 24 months
Secondary Outcomes
- Glycemic Control - Insulin doses, TDI overall(24 months)
- Glycemic Control - Insulin doses, TDI 0-6 months(6 months)
- Glycemic Control - Insulin doses, basal insulin 0-6 months(6 months)
- Triple Label tracer (both substudies): Change in Rate of Glucose Appearance (Ra)(24 months)
- Glycemic Control - Insulin doses, TDI 6-12 months(months 18-24)
- Glycemic Control - Insulin doses, TDI 18-24 months(months 18-24)
- Glycemic Control - Insulin doses, basal insulin 6-12 months(months 6-12)
- Glycemic Control - Insulin doses, insulin:carb ratio 6-12 months(months 6-12)
- Triple Label Tracer, Difference in overall Hepatic SI at 24 months(2 years)
- Glycemic Control - Insulin doses, insulin:carb ratio overall(24 months)
- Triple Label tracer (both substudies): Change in Endogenous Glucose Production (EGP)(24 months)
- Randomized Substudy: Comparison of Glycemic Control (below also) - Time in range, overall(2 years)
- Glycemic Control - Time in range, months 6-12(months 6-12)
- Glycemic Control - Time in range, months 12-18(months 12-18)
- Glycemic Control - Insulin doses, basal insulin total(24 months)
- Triple Label tracer (both substudies): Change in Rate of Glucose Disappearance (Rd)(24 months)
- Glycemic Control - Time in range, months 0-6(6 months)
- Glycemic Control - Insulin doses, basal insulin 12-18 months(months 12-18)
- Glycemic Control - Insulin doses, basal insulin 18-24 months(months 18-24)
- Glycemic Control - Insulin doses, insulin:carb ratio 12-18 months(months 12-18)
- Glycemic Control - Insulin doses, insulin sensitivity factor 0-6 months(6 months)
- Glycemic Control - Insulin doses, insulin sensitivity factor 6-12 months(months 6-12)
- Glycemic Control - Time in range, months 18-24(months 18-24)
- Glycemic Control - Insulin doses, TDI 12-18 months(months 12-18)
- Glycemic Control - Insulin doses, insulin:carb ratio 18-24 months(months 18-24)
- Glycemic Control - Insulin doses, insulin:carb ratio 0-6 months(6 months)
- Glycemic Control - Differences in CGM readings over prior month, Time 70-180 mg/dL(24 months)
- Glycemic Control - Differences in CGM readings over prior month, Time >250 mg/dL(24 months)
- Glycemic Control - Differences in CGM readings over prior month, Number of hypoglycemia events(24 months)
- Triple Label Tracer, Difference in overall insulin sensitivity (SI) at 12 months(1 year)
- Triple Label Tracer, Change in overall Hepatic SI at 24 months(2 years)
- Triple Label Tracer, Change in Peripheral SI at 24 months(2 years)
- Triple Label Tracer, Change in Peripheral SI at 12 months(1 year)
- Triple Label Tracer, Change in Endogenous glucose uptake at 24 months(2 years)
- Triple Label Tracer, Change in Glucose uptake at 12 months(1 year)
- Triple Label Tracer, Difference in Meal glucose uptake at 24 months(2 years)
- Triple Label Tracer, Difference in Meal glucose uptake at 12 months(1 year)
- Triple Label Tracer, Change in Meal glucose uptake at 24 months(2 years)
- Glycemic Control - Insulin doses, insulin sensitivity factor overall(24 months)
- Glycemic Control - Insulin doses, insulin sensitivity factor 12-18 months(months 12-18)
- Glycemic Control - Differences in CGM readings over prior month, Time >180 mg/dL(24 months)
- Glycemic Control - Differences in CGM readings over prior month, Total daily insulin injected(24 months)
- Randomized substudy: Triple Label Tracer, Change in insulin sensitivity (SI) at 12 months(1 year)
- Glycemic Control - Insulin doses, insulin sensitivity factor 18-24 months(months 18-24)
- Triple Label Tracer, Difference in overall insulin sensitivity (SI) at 24 months(2 years)
- Randomized substudy: Triple Label Tracer, Change in insulin sensitivity (SI) at 24 months(2 years)
- Triple Label Tracer, Change in overall Hepatic SI at 12 months(1 year)
- Triple Label Tracer, Difference in Peripheral SI at 12 months(1 year)
- Glycemic Control - Differences in CGM readings over prior month, Time <70 mg/dL(24 months)
- Triple Label Tracer, Difference in overall Hepatic SI at 12 months(1 year)
- Triple Label Tracer, Difference in Peripheral SI at 24 months(2 years)
- Triple Label Tracer, Difference in Endogenous glucose uptake at 24 months(2 years)
- Triple Label Tracer, Change in Endogenous glucose uptake at 12 months(1 year)
- Triple Label Tracer, Difference in Glucose uptake at 24 months(2 years)
- Triple Label Tracer, Difference in Endogenous glucose uptake at 12 months(1 year)
- Triple Label Tracer, Change in Meal glucose uptake at 12 months(1 year)
- Triple Label Tracer, Difference in Glucose uptake at 12 months(1 year)
- Triple Label Tracer, Change in Glucose uptake at 24 months(2 years)
- Division of diabetes management responsibilities, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Division of diabetes management responsibilities, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Division of diabetes management responsibilities, parent, difference in score at 24 months (adjusted for baseline)(24 months)
- Peer influence, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Diabetes distress, parent, difference in score at 12 months (adjusted for baseline)(12 months)
- Depression in child, assessed by parent, difference in score at 24 months (adjusted for baseline)(24 months)
- Division of diabetes management responsibilities, parent, difference in score at 12 months (adjusted for baseline)(12 months)
- Family conflict, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Family conflict, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Family conflict, parent, difference in score at 24 months (adjusted for baseline)(24 months)
- Family conflict, parent, difference in score at 12 months (adjusted for baseline)(12 months)
- Peer influence, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Fear of hypoglycemia, parent, difference in score at 12 months (adjusted for baseline)(12 months)
- Depression, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Depression, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Technology acceptance, parent, difference in score at 24 months (adjusted for baseline)(24 months)
- Diabetes distress, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Diabetes distress, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Depression in child, assessed by parent, difference in score at 12 months (adjusted for baseline)(12 months)
- Technology acceptance, parent, difference in score at 12 months (adjusted for baseline)(12 months)
- Health-related quality of life, parent, difference in score at 24 months (adjusted for baseline)(24 months)
- Health-related quality of life, parent, difference in score at 12 months (adjusted for baseline)(12 months)
- Both substudies: Change in HbA1c(24 months)
- Both substudies: Change in percent time-in-range 70-180 mg/dL (TIR)(24 months)
- Both substudies: Change in percent time <70 mg/dL(24 months)
- Diabetes distress, parent, difference in score at 24 months (adjusted for baseline)(24 months)
- Fear of hypoglycemia, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Fear of hypoglycemia, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Fear of hypoglycemia, parent, difference in score at 24 months (adjusted for baseline)(24 months)
- Health-related quality of life, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Technology acceptance, child, difference in score at 12 months (adjusted for baseline)(12 months)
- Technology acceptance, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Health-related quality of life, child, difference in score at 24 months (adjusted for baseline)(24 months)
- Both substudies: Change in percent time >180 mg/dL(24 months)