Relieving Carb Counting Via Flexible-userinteraction Multiple-input Control Architectures

Official title

Beyond Hybrid Artificial Pancreas Systems: Relieving Carb Counting Via Flexible-userinteraction Multiple-input Control Architectures

Overview

Developing algorithms for Automated Insulin Delivery (AID) systems that alleviate the burden of meal announcements, culminating in the FLEX-AP system. This fully automated artificial pancreas system is designed to operate without meal or exercise announcements while allowing for optional user input. FLEX-APaims to achieve a balance between glycemic control and user quality of life by incorporating user preferences into its operation. The FLEX-AP system features a flexible control architecture tailored to handle unannounced meals and exercise. It also allows for optional meal announcements and offers guidance for mitigating hypoglycemia, such as counterregulatory actions like rescue carbohydrate intake for patients who prefer it. The proposed benefit of FLEX-AP is to improve glycemic control while respecting individual preferences, which sets it apart from existing AID systems.

Detailed description

Although AID systems have significantly advanced, carbohydrate counting remains a burdensome and error-prone task for patients, often leading to suboptimal postprandial glycemic control. Furthermore, even with accurate carbohydrate estimation, other macronutrients impact glycemic responses, complicating management. Hybrid AID systems that rely on meal announcements to manage glycemic excursions, but theses exhibit a limited efficacy when managing moderate-to-large unannounced meals, underscoring the need for systems with improved adaptability and functionality.

The FLEX-AP system features a flexible control architecture tailored to handle unannounced meals and exercise. It also allows for optional meal announcements and offers guidance for mitigating hypoglycemia, such as counterregulatory actions like rescue carbohydrate intake for patients who prefer it. The proposed benefit of FLEX-AP is to improve glycemic control while respecting individual preferences, which sets it apart from existing AID systems.

The first clinical trial that uses the FLEX-AP system (NCT06082973) was approved by the Spanish regulatory agency (AEMPS) in April 2024 and it is currently ongoing. This study evaluates the FLEX-AP in a hospital setting under unannounced exercise challenges to assess the functionality of counter-regulatory actions recommendation, comparing rescue carbohydrates versus mini-doses of glucagon.

The rationale of this study is to advance the evaluation of the FLEX-AP system for fully automated postprandial glucose control under inpatient and outpatient conditions, going beyond in-silico studies. This study is designed to determine safety and efficacy of the FLEX-AP system in a controlled ambulatory condition, emulating real-life conditions. Patients will operate the system as fully-automated for meals under 70 grams of carbohydrates, announcing larger meals as safety measure in this first ambulatory study. This study will provide essential insights for engineers to understand complex meal dynamics better, facilitating further refinement of the FLEX-AP algorithm required for pivotal studies.

Interventions

• Device FLEX-AP system will be implemented to T1D patients
  A FLEX-AP system will be implemented to T1D patients after they have been given a Minimed 780G hybrid closed-loop system

Primary outcome measures

• Efficacy of the FLEX-AP system [Time frame: 4 weeks]
• Safety of the FLEX-AP system [Time frame: 4 weeks]

Secondary outcome measures (12)

• Continuous glucose monitoring (CGM) data during the FLEX-AP controlled ambulatory phase in automatic mode will be analyzed according to the following standardized CGM metrics for clinical trials. [Time frame: 4 weeks]
• Continuous glucose monitoring (CGM) data during the FLEX-AP controlled ambulatory phase in automatic mode will be analyzed according to the following standardized CGM metrics for clinical trials. [Time frame: 4 weeks]
• Continuous glucose monitoring (CGM) data during the FLEX-AP controlled ambulatory phase in automatic mode will be analyzed according to the following standardized CGM metrics for clinical trials. [Time frame: 4 weeks]
• Continuous glucose monitoring (CGM) data during the FLEX-AP controlled ambulatory phase in automatic mode will be analyzed according to the following standardized CGM metrics for clinical trials. [Time frame: 4 weeks]
• Continuous glucose monitoring (CGM) data during the FLEX-AP controlled ambulatory phase in automatic mode will be analyzed according to the following standardized CGM metrics for clinical trials. [Time frame: 4 weeks]
• Continuous glucose monitoring (CGM) data during the FLEX-AP controlled ambulatory phase in automatic mode will be analyzed according to the following standardized CGM metrics for clinical trials. [Time frame: 4 weeks]
• Continuous glucose monitoring (CGM) data during the FLEX-AP controlled ambulatory phase in automatic mode will be analyzed according to the following standardized CGM metrics for clinical trials. [Time frame: 4 weeks]
• The glycemic outcome within the postprandial period will be assessed, in an exploratory analysis, with the 5-h postprandial percent TIR (70-180 mg/dL) [Time frame: 4 weeks]
• The glycemic outcome within the postprandial period will be assessed, in an exploratory analysis, the 5-h postprandial glucose incremental area under the curve. [Time frame: 4 weeks]
• Efficacy of the FLEX-AP system [Time frame: 4 weeks]
• Efficacy of the FLEX-AP system [Time frame: 4 weeks]
• Efficacy of the FLEX-AP system [Time frame: 4 weeks]

Eligibility criteria

Inclusion criteria

• Aged 18-60 years inclusive.
• T1D as per the American Diabetes Association classification for >12 months prior to the screening visit.
• Minimed 780G®-hybrid closed-loop system users for at least 6 months. Use of automatic mode (Smartguard) > 80% of the time.
• A1c level below 9.0% at Screening visit.
• Assessment of albuminuria and retinal tests, which should have yielded negative results for advanced medical complications.
• Willing and able to adhere to the study protocol

Exclusion criteria

• Not having met the previous criteria for inclusion.
• Females who are pregnant or intend to become pregnant during the study period; a positive pregnancy test at screening will result in exclusion.
• Breastfeeding.
• Use of any non-insulin glucose-lowering therapy within three months prior to study initiation.
• Presence of moderate/severe renal impairment, defined as an estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m².
• History of severe hypoglycemia (defined as coma or convulsion requiring assistance from others) or diabetic ketoacidosis in the six months prior to study initiation.
• Hypoglycemia unawareness (defined as Clarke Test score greater than 3).
• Occurrence of an acute cardiovascular event (e.g., myocardial infarction, unstable angina, stroke) within twelve months prior to study initiation.
• History of drug or alcohol abuse. History of any active or suspected malignancy.
• Clinically significant microvascular complications (such as macroalbuminuria, preproliferative and proliferative retinopathy), cardiovascular, hepatic, neurological, endocrine, or other systemic conditions, apart from T1D, that may hinder the implementation of the clinical study protocol or the interpretation of study results.
• Diabetic gastroparesis.
• Scheduled surgery during the study period.
• Adherence to a very low carbohydrate diet, defined as a carbohydrate intake of less than 40 grams per day.
• Presence of any comorbid medical or psychological condition deemed by the investigators to render the individual unsuitable for study participation.
• Known allergy to insulin NovoRapid.
• Regular practice of competitive or very high intensity physical activity.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital Universitario Ramón y Cajal — Madrid

Publications

• Shalit R, Minsky N, Laron-Hirsh M, Cohen O, Kurtz N, Roy A, Grosman B, Benedetti A, Tirosh A. Unannounced Meal Challenges Using an Advanced Hybrid Closed-Loop System. Diabetes Technol Ther. 2023 Sep;25(9):579-588. doi: 10.1089/dia.2023.0139. PMID 37335759
• Tornese G, Carletti C, Giangreco M, Nistico D, Faleschini E, Barbi E. Carbohydrate Tolerance Threshold for Unannounced Snacks in Children and Adolescents With Type 1 Diabetes Using an Advanced Hybrid Closed-Loop System. Diabetes Care. 2022 Jun 2;45(6):1486-1488. doi: 10.2337/dc21-2643. PMID 35522033

Identifiers

NCT: NCT07031492 · FLEX-AP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗