Artificial Pancreas for Type 1 Diabetes

(AP APPLE Trial)

Overseen By Lianna Smith

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Virginia

Must be taking: Insulin

Must not be taking: Non-insulin glucose-lowering agents

Disqualifiers: Severe renal impairment, Psychiatric treatment, Adrenal disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 24 months

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop using any non-insulin glucose-lowering medications during the trial. If you are not already using lispro (Humalog) or aspart (Novolog), you will need to switch to one of these insulins for the study. You also need to stop using any personal continuous glucose monitor (CGM) once the study CGM is in use.

Is the artificial pancreas safe for humans?

Research shows that the artificial pancreas has been tested for safety in both adults and adolescents with type 1 diabetes. Studies have focused on ensuring the device safely manages blood sugar levels, and while there are still areas to improve, it has been generally considered safe in clinical trials. ^{1 2 3 4 5}

How is the artificial pancreas treatment different from other treatments for type 1 diabetes?

The artificial pancreas is unique because it automatically regulates blood sugar levels by delivering insulin and sometimes glucagon, reducing the need for constant monitoring and manual insulin injections. This system is particularly beneficial for managing unannounced meals and varying glucose responses, offering a more automated and precise approach compared to traditional insulin therapy. ^{1 2 3 6 7}

What data supports the effectiveness of the treatment Artificial Pancreas (AP) for Type 1 Diabetes?

Research shows that the artificial pancreas (AP) helps manage blood sugar levels in people with type 1 diabetes by automatically adjusting insulin delivery, which can improve the time spent in the target blood sugar range and reduce the risk of low blood sugar episodes. ^{1 3 4 7 8}

Who Is on the Research Team?

Mark DeBoer, MD

Principal Investigator

UVA Center for Diabetes Technology

Are You a Good Fit for This Trial?

This trial is for pubertal adolescents aged 11 to under 13 with Type 1 Diabetes, who have been using insulin for at least six months and have an HbA1c level below 10%. Participants need internet access to upload data and must not be pregnant or planning pregnancy. They should agree to use only specified insulins if assigned to the Control-IQ group.

Inclusion Criteria

Participants must have Internet access and a computer system that meets the requirements for uploading the study equipment.

Access to internet and willingness to upload data during the study as needed

I have started puberty.

Exclusion Criteria

Your blood sugar level, as measured by hemoglobin A1c, is higher than 10% in 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, Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment, Pregnancy or intent to become pregnant during the trial, Currently being treated for a seizure disorder, Planned surgery during study duration, Treatment with any non-insulin glucose-lowering agent (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals), A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol, Use of an insulin delivery mechanism that is not downloadable by the subject or study team, (Randomized substudy only) 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), Having a family member(s) employed by Tandem Diabetes Care, Inc. or Dexcom, Inc., Current enrollment in another clinical trial, unless approved by the investigator of both studies or if clinical trial is a non-interventional registry trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Device Training

Participants undergo a virtual or in-person device training session to improve adherence

1 session

1 visit (in-person or virtual)

Treatment

Participants are involved in either the Randomized or Triple Label Surveillance substudy, with continuous CGM data collection and periodic assessments

24 months

3 visits (in-person or virtual) at yearly intervals

Follow-up

Participants are monitored for changes in insulin resistance and glycemic control, with additional phone calls for data collection

24 months

Additional phone calls and remote monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Artificial Pancreas (AP)

Trial Overview The study tests how well an Artificial Pancreas (AP) controls Type 1 Diabetes in adolescents over two years. It includes a randomized controlled trial where participants are randomly placed into groups, and an observational study without intervention changes.

How Is the Trial Designed?

Group I: Randomized substudy: Artificial Pancreas Therapy Experimental Treatment 1 Intervention

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

Group II: Randomized substudy: Usual Care + CGM Active Control 1 Intervention

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

Group III: Triple Label Surveillance substudy (observational arm) Active Control 1 Intervention

Participants will remain on own baseline diabetes management (e.g. automated insulin delivery system, non-AID pump, MDI)

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

DexCom, Inc.

Industry Sponsor

Trials

151

Recruited

35,700+

Kevin Sayer

DexCom, Inc.

Chief Executive Officer since 2015

Bachelor’s and Master’s degrees in Accounting and Information Systems from Brigham Young University

Dr. Shelly Lane

DexCom, Inc.

Chief Medical Officer since 2023

MD from University of California, San Diego

Tandem Diabetes Care, Inc.

Industry Sponsor

Trials

43

Recruited

5,800+

Published Research Related to This Trial

The open-source AndroidAPS (AAPS) hybrid closed-loop system significantly improved the percentage of time in range (TIR) for participants with type 1 diabetes, increasing it by 18.6% compared to stand-alone insulin pump therapy (76.6% vs. 58.0%).

The AAPS system demonstrated comparable safety to traditional pump therapy, with no serious adverse events or severe hypoglycemia reported, indicating it is a safe option for managing blood glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid Closed Loop Using a Do-It-Yourself Artificial Pancreas System in Adults With Type 1 Diabetes. Nanayakkara, N., Sharifi, A., Burren, D., et al.[2023]

Hybrid closed-loop insulin delivery systems, known as artificial pancreas (AP), significantly improve glucose control in children and adolescents with type 1 diabetes, increasing the time spent in the target glucose range without raising the risk of hypoglycemia.

Despite the effectiveness of these systems for overnight glycemic control, daytime management remains challenging, highlighting the need for careful meal planning and bolusing, as fully automated systems are still under investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artificial Pancreas Technology Offers Hope for Childhood Diabetes. Schoelwer, MJ., DeBoer, MD.[2022]

Focus groups with 15 parents and 5 pediatric endocrinologists highlighted the need for modifications to artificial pancreas systems to make them safer and more effective for children aged 5-8 years with type 1 diabetes, emphasizing features like customizable access and enhanced monitoring.

Parents and physicians expressed strong interest in having artificial pancreas applications for younger children, stressing that these systems should include child-specific functionalities and safety features to improve diabetes management and communication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the Safety and Functionality of an Artificial Pancreas System for Use in Younger Children: Input from Parents and Physicians. Gildersleeve, R., Riggs, SL., Cherñavvsky, DR., et al.[2018]

Citations

1. Denmark pubmed.ncbi.nlm.nih.gov

Use of an artificial pancreas among adolescents for a missed snack bolus and an underestimated meal bolus. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Hybrid Closed Loop Using a Do-It-Yourself Artificial Pancreas System in Adults With Type 1 Diabetes. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Artificial Pancreas Technology Offers Hope for Childhood Diabetes. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Twelve-Week 24/7 Ambulatory Artificial Pancreas With Weekly Adaptation of Insulin Delivery Settings: Effect on Hemoglobin A1c and Hypoglycemia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Improving the Safety and Functionality of an Artificial Pancreas System for Use in Younger Children: Input from Parents and Physicians. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

A Review of Safety and Hazards Associated With the Artificial Pancreas. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

A New Meal Absorption Model for Artificial Pancreas Systems. [2022]