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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an artificial pancreas system to help manage Type 1 Diabetes in young teens. Researchers aim to assess how well this system controls blood sugar levels over two years. Participants will either use the artificial pancreas or continue their usual care. The trial seeks teens around 11-12 years old who have managed Type 1 Diabetes for at least a year and are using insulin.

As an unphased trial, this study offers participants a unique opportunity to contribute to innovative diabetes management research.

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.

What prior data suggests that the Artificial Pancreas is safe for adolescents with Type 1 Diabetes?

Research has shown that the Artificial Pancreas (AP) system, specifically the Tandem t:slim X2 with Control-IQ technology, is generally safe for children and teens with Type 1 Diabetes. One study found that young children aged 2 to 5 used this system safely and achieved better blood sugar control. Another study demonstrated that the system improved blood sugar management and overall well-being in daily life.

Other research has examined the safety of this device across different age groups, including children, teens, and young adults, and confirmed its safety. While these results are encouraging, individual experiences can vary, so discussing any concerns with healthcare providers is always recommended. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Artificial Pancreas (AP) is unique because it automates insulin delivery, potentially offering better blood sugar control for people with Type 1 Diabetes. Unlike traditional treatments like multiple daily injections or insulin pumps, which require constant user input, the AP uses advanced technology to monitor glucose levels and adjust insulin doses in real-time. Researchers are excited about this system because it could reduce the burden of managing diabetes and minimize the risk of both high and low blood sugar episodes, leading to a more balanced and hassle-free lifestyle for patients.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

Research shows that the Tandem t:slim X2 with Control-IQ technology, part of the Artificial Pancreas (AP) system, helps people with Type 1 Diabetes maintain stable blood sugar levels. In this trial, participants in the "Randomized substudy: Artificial Pancreas Therapy" arm will use this system for two years. Earlier studies found that users of this system kept their blood sugar levels within the target range more frequently, without an increase in dangerous low blood sugar episodes. Additionally, real-world data indicates that people felt better overall and found it easier to manage their diabetes with the AP system. These findings suggest that the AP system can effectively help control Type 1 Diabetes. ^{2 6 7 8 9}

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6909715/

Successful At-Home Use of the Tandem Control-IQ Artificial ... The use of the Tandem t:slim X2 with Control-IQ HCL AP system significantly improved time in range and mean glycemic control without increasing hypoglycemia.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7868573/

Real-World Patient-Reported Outcomes and Glycemic ... Conclusions: Continued real-world use of the t:slim X2 pump with Control-IQ technology showed improvements in psychosocial outcomes and persistent achievement ...

3. tandemdiabetes.com tandemdiabetes.com/providers/clinical-evidence

Clinical Evidence | Tandem Diabetes Care RX ONLY. The t:slim X2 pump with interoperable technology (the pump) and Control-IQ+ technology (Control-IQ+) are intended for single patient use.

4. tandfonline.com tandfonline.com/doi/full/10.1080/17434440.2025.2585061

An overview of the t:slim X2 and Mobi insulin pumps with ... Real-world glycemic and person-reported outcomes after Tandem Control-IQ initiation in children with type 1 diabetes. J Clin Endocrinol ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168822724000275

Patient reported outcomes (PROs) and user experiences of ... Examine patient-reported outcomes (PROs) after the use of t:slim X2 insulin pump with Control-IQ technology (CIQ) in young children with type 1 diabetes.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8080923/

Safety and Performance of the Tandem t:slim X2 with ... In this brief pilot study, use of the modified Control-IQ system was safe in 2–5-year-old children with T1D and improved glycemic control.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04084171

Safety of Artificial Pancreas Therapy in Preschoolers, Age 2-6 This clinical trial aims to demonstrate the safety of the Closed-Loop Control (CLC), also known as Artificial Pancreas (AP) named t:slim X2 with Control-IQ ...

8. link.springer.com link.springer.com/article/10.1007/s13300-024-01618-2

Safety and Psychological Outcomes of Tandem t:Slim X2 ... We reviewed the current evidence about the psychological, safety, and exercise-related outcomes of this device in children, adolescents, and young adults ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03844789

A Study of t:Slim X2 With Control-IQ Technology (DCLP5) The purpose of this study is to learn whether an investigational automated insulin delivery system ("study system") for children with type 1 diabetes can ...