Clinical trial NCT05876273: Neural-net Artificial Pancreas (NAP)
Official title: Adaptive Motif-Based Control (AMBC): Pilot 1 - Neural Net Implementation of Automated Insulin Delivery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type1 Diabetes
Keywords: Artificial Pancreas (AP)
Diabetes Mellitus, Type 1
Insulin Pump
Continuous Glucose Monitor (CGM)
Model Predictive Control (MPC)
Automated Insulin Delivery (AID)
Adaptive Motif-based Control (AMBC)
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-05-25
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized crossover: Participants will be randomized to two groups differing by the order of controller use: Group A: NAP, followed by UMPC; Group B: UMPC, followed by NAP.
Primary purpose: TREATMENT

Brief summary: This study is intended to assess a Neural-net Artificial Pancreas (NAP) implementation of an established AP controller - the University of Virginia Model Predictive Control Algorithm (UMPC). The health outcomes achieved on NAP will be compared to the health outcomes achieved on UMPC in a randomized crossover design. The investigators will consent up to 20 participants, ages ≥18.0, with a goal of completing 15 participants.

Detailed description: The study will follow a randomized cross-over design assessing glycemic control on a Neural-net Artificial Pancreas (NAP), compared to the previously tested University of Virginia Model Predictive Control (UMPC) algorithm, in a supervised hotel setting:

The study will involve Tandem t:slim X2 Control-IQ (CIQ) users who will continue to use their CIQ systems, except during the hotel sessions, which will use the DiAs prototyping platform, connected to a Tandem t:AP research pump and a Dexcom G6 sensor, and implementing NAP or UMPC. The study sensor will be the same sensor used by CIQ - it will be disconnected from CIQ and connected to DiAs.

Following enrollment, one week of automated insulin delivery (AID) data will be downloaded from the participants' pumps or t:connect accounts and will be used to establish a baseline and initialize the control algorithms. Participants will be then studied at a local hotel for 20 hours, including an 18-hour experiment, randomly receiving either NAP or UMPC. Participants will then receive the opposite intervention either sequentially during the same hotel stay, or in a second hotel stay up to 28 days following the first hotel stay. During these 18-hour hotel sessions participants will be followed to compare blood glucose control on NAP vs. UMPC. The study meals and activities will be kept the same between study sessions.

The investigators will analyze non-inferiority of NAP compared to UMPC, but this pilot feasibility study is not powered to formally test noninferiority. The primary outcome is percent time in range (TIR) (70 to 180 mg/dL) on NAP vs UMPC. Secondary outcomes include frequency of hypoglycemia (time below range = TBR) and hyperglycemia (time above range = TAR), as well as other safety and control metrics.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18.0 at time of consent.
2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year.
3. Currently using insulin for at least six months.
4. Currently using the Control-IQ automated insulin delivery system for at least one mont.
5. Hemoglobin A1c of ≤9%.
6. Using insulin parameters such as insulin to carb ratio and correction factor consistently in order to dose insulin for meals or corrections.
7. Access to internet and willingness to upload data during the study as needed.
8. If female of childbearing potential 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 within 24 hours prior to initiating the experimental algorithms. 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.
9. Willingness to use the University of Virginia Diabetes Assistant system throughout study session.
10. Willingness to use personal Lispro (Humalog) or aspart (Novolog) during the study session.
11. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial (including Sodium-glucose cotransporter-2 inhibitors, metformin/biguanides, glucagon-like peptide-1 receptor agonists, Pramlintide, Dipeptidyl peptidase-4 inhibitors, Sulfonylureas and nutraceuticals).
12. Willingness to reschedule the hotel portion of the study if placed on systemic steroids (e.g. intravenous injection, intramuscular injection, intra-articular or oral routes).
13. An understanding and willingness to follow the protocol and signed informed consent.

Exclusion Criteria:

1. History of Diabetic Ketoacidosis (DKA) in the 12 months prior to enrollment.
2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment.
3. Currently pregnant or intent to become pregnant during the trial.
4. Currently breastfeeding.
5. Currently being treated for a seizure disorder.
6. Treatment with Meglitinides/Sulfonylureas at the time of hotel study.
7. Use of metformin/biguanides, glucagon-like peptide-1 agonists, Pramlintide, Dipeptidyl peptidase-4 inhibitors, Sodium-glucose cotransporter-2 inhibitors, or nutraceuticals intended for glycemic control with a change in dose in the past month.
8. History of significant cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted or previous ablation of arrhythmia without recurrence which may be permitted) or active cardiovascular disease.
9. 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. Inpatient psychiatric treatment in the past 6 months.
   2. Presence of a known adrenal disorder.
   3. Uncontrolled thyroid disease.
10. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol.

Primary outcomes:
measure: Percent of Time-in-Range (TIR) on NAP Versus UMPC.
timeFrame: 36 hours (two 18-hour experiments)
Secondary outcomes:
measure: Percent of Time in Hyperglycemia.
timeFrame: 36 hours (two 18-hour experiments)
measure: Percent of Time in Hypoglycemia.
timeFrame: 36 hours (two 18-hour experiments)
measure: System Functionality
timeFrame: 36 hours (two 18-hour experiments)
measure: Participant Feedback
timeFrame: 36 hours (two 18-hour experiments)
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Center for Diabetes Technology
state: Virginia
Study officials:
affiliation: University of Virginia Center for Diabetes Technology
name: Boris P Kovatchev, PhD
role: STUDY_DIRECTOR
affiliation: University of Virginia Center for Diabetes Technology
name: Sue A Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kovatchev B, Castillo A, Pryor E, Kollar LL, Barnett CL, DeBoer MD, Brown SA. Neural-Net Artificial Pancreas: A Randomized Crossover Trial of a First-in-Class Automated Insulin Delivery Algorithm. Diabetes Technol Ther. 2024 Jun;26(6):375-382. doi: 10.1089/dia.2023.0469.