Artificial Pancreas - Adolescent Physiology & Psychology Longitudinal Evaluation

Artificial Pancreas - Adolescent Physiology & Psychology Longitudinal Evaluation

Sponsors

Lead Sponsor: University of Virginia

Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
DexCom, Inc.
Tandem Diabetes Care, Inc.

Source University of Virginia
Brief Summary

This is a longitudinal randomized controlled study designed to assess changes in control of Type 1 Diabetes in pubertal adolescents over a two year period.

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 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. 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 insulin pumps or multiple daily injections [MDI]). The Experimental Group will use an AP system during the two year duration of the study. The primary outcome will be HbA1c between groups at the 24-month visit. Following confirmation of eligibility participants will be assessed at Visit 1, with assessments described further below. Randomization will occur at the end of Visit 2. A Run-In Period of 2 weeks will be required for participants who do not have prior CGM experience or MDI participants who have no prior insulin pump experience. Participants will undergo a Triple-Labeled Glucose Assessment at months 0, 12 and 24. This assessment is to evaluate the degree of insulin resistance including in the hepatic and peripheral compartments. They will also complete multiple questionnaires assessing aspects of adolescent psychology and sociology. HbA1c will also be collected using a local lab. 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 Experimental 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 21 child/parent dyads in each of the two study arms.

Overall Status Recruiting
Start Date September 2020
Completion Date August 30, 2024
Primary Completion Date August 17, 2024
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
The 24-month HbA1c between AP system and Usual Care+CGM groups, performed as regression, adjusted for baseline HbA1c. 2 years
Secondary Outcome
Measure Time Frame
Glycemic Control - Time in range, overall 2 years
Glycemic Control - Time in range, months 0-6 6 months
Glycemic Control - Time in range, months 6-12 months 6-12
Glycemic Control - Time in range, months 12-18 months 12-18
Glycemic Control - Time in range, months 18-24 months 18-24
Glycemic Control - Insulin doses, TDI overall 24 months
Glycemic Control - Insulin doses, TDI 0-6 months 6 months
Glycemic Control - Insulin doses, TDI 6-12 months months 18-24
Glycemic Control - Insulin doses, TDI 12-18 months months 12-18
Glycemic Control - Insulin doses, TDI 18-24 months months 18-24
Glycemic Control - Insulin doses, basal insulin total 24 months
Glycemic Control - Insulin doses, basal insulin 0-6 months 6 months
Glycemic Control - Insulin doses, basal insulin 6-12 months months 6-12
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 overall 24 months
Glycemic Control - Insulin doses, insulin:carb ratio 0-6 months 6 months
Glycemic Control - Insulin doses, insulin:carb ratio 6-12 months months 6-12
Glycemic Control - Insulin doses, insulin:carb ratio 12-18 months months 12-18
Glycemic Control - Insulin doses, insulin:carb ratio 18-24 months months 18-24
Glycemic Control - Insulin doses, insulin sensitivity factor overall 24 months
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 - Insulin doses, insulin sensitivity factor 12-18 months months 12-18
Glycemic Control - Insulin doses, insulin sensitivity factor 18-24 months months 18-24
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 <70 mg/dL 24 months
Glycemic Control - Differences in CGM readings over prior month, Time >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
Glycemic Control - Differences in CGM readings over prior month, Total daily insulin injected 24 months
Triple Label Tracer, Difference in overall insulin sensitivity (SI) at 24 months 2 years
Triple Label Tracer, Difference in overall insulin sensitivity (SI) at 12 months 1 year
Triple Label Tracer, Change in insulin sensitivity (SI) at 24 months 2 years
Triple Label Tracer, Change in insulin sensitivity (SI) at 12 months 1 year
Triple Label Tracer, Difference in overall Hepatic SI at 24 months 2 years
Triple Label Tracer, Difference in overall Hepatic SI at 12 months 1 year
Triple Label Tracer, Change in overall Hepatic 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 24 months 2 years
Triple Label Tracer, Difference in Peripheral SI at 12 months 1 year
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, Difference in Endogenous 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 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 Glucose uptake at 12 months 1 year
Triple Label Tracer, Change in 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
Triple Label Tracer, Change in Meal glucose uptake at 12 months 1 year
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
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
Peer influence, child, difference in score at 12 months (adjusted for baseline) 12 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
Diabetes distress, parent, difference in score at 24 months (adjusted for baseline) 24 months
Diabetes distress, parent, difference in score at 12 months (adjusted for baseline) 12 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
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
Depression in child, assessed by parent, difference in score at 24 months (adjusted for baseline) 24 months
Depression in child, assessed by parent, 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
Technology acceptance, 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
Technology acceptance, parent, difference in score at 12 months (adjusted for baseline) 12 months
Health-related quality of life, child, 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
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
Enrollment 100
Condition
Intervention

Intervention Type: Device

Intervention Name: Artificial Pancreas (AP)

Description: The AP system used in this trial is the Tandem t:slim insulin pump with Control-IQ Technology. This system is FDA approved for use starting at age 14 years.

Arm Group Label: Artificial Pancreas Therapy

Eligibility

Criteria:

Inclusion Criteria: 1. Age 11 to <13 years (at time of enrollment) with a parent/guardian (18+ yo) who is willing to participate with the child 2. At least Tanner 2 pubic hair (boys), Tanner 2 breast development (girls) 3. 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.. 4. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year 5. Currently using insulin for at least six months 6. 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 7. Access to internet and willingness to upload data during the study as needed 8. For females, not currently known to be pregnant or breastfeeding 9. 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. 10. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use 11. Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study, if randomized to the Control-IQ group. 12. Total daily insulin dose (TDD) at least 10 U/day and not more than 100 U/day 13. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, biguanides, sulfonylureas and naturaceuticals) 14. An understanding and willingness to follow the protocol and signed informed consent 15. Participants must have Internet access and a computer system that meets the requirements for uploading the study equipment. Exclusion Criteria: 1. Hemoglobin A1c >10% clinically obtained within the past 6 weeks 2. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples: 1. Severe renal impairment, end-stage renal disease, or dialysis 2. Inpatient psychiatric treatment in the past six months 3. Presence of a known adrenal disorder 4. 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 5. Uncontrolled thyroid disease 6. Concurrent use of any non-insulin glucose-lowering agent. 7. Hemophilia or any other bleeding disorder. 3. History of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment 4. Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment 5. Pregnancy or intent to become pregnant during the trial 6. Currently being treated for a seizure disorder 7. Planned surgery during study duration 8. Treatment with any non-insulin glucose-lowering agent (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals) 9. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol 10. Use of an insulin delivery mechanism that is not downloadable by the subject or study team 11. Current use of an automated insulin delivery system (besides LGS and PLGS) such as Medtronic 670G, Control-IQ or DIY system (or unwillingness to discontinue automated insulin delivery for three months before enrollment and the duration of the trial). 12. Having a family member(s) employed by Tandem Diabetes Care, Inc. or Dexcom, Inc. 13. Current enrollment in another clinical trial, unless approved by the investigator of both studies or if clinical trial is a non-interventional registry trial.

Gender: All

Minimum Age: 11 Years

Maximum Age: 13 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Mark D. DeBoer, MD, MSc, MCR Principal Investigator UVA Center for Diabetes Technology
Overall Contact

Last Name: Mark D DeBoer, MD, MSc, MCR

Phone: (434) 924-5956

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: University of Virginia Center for Diabetes Technology Mark D DeBoer, MD 434-924-9833 [email protected] Marc D Breton, PhD Sub-Investigator Ananda Basu, MD FRCP Sub-Investigator Chaira Fabris, PhD Sub-Investigator Boris P Kovatchev, PhD Sub-Investigator Melissa Schoelwer, MD Sub-Investigator Jaclyn Shepard, PsyD Sub-Investigator
Location Countries

United States

Verification Date

September 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Virginia

Investigator Full Name: Mark D. DeBoer, MD, MSc., MCR

Investigator Title: Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Artificial Pancreas Therapy

Type: Experimental

Description: Participants will use a study assigned Tandem t:slim X2 with Control-IQ Technology.for two years.

Label: Usual Care + CGM

Type: No Intervention

Description: Participant will use their usual diabetes care along with a study CGM.

Acronym AP APPLE
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: This is a longitudinal randomized controlled study designed to assess changes in control of Type 1 Diabetes in pubertal adolescents over a two year period.

Primary Purpose: Other

Masking: None (Open Label)

Source: ClinicalTrials.gov