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

Not Applicable

Not yet recruiting

• Conditions: T1DM - Type 1 Diabetes Mellitus

• Registration Number: NCT07031492
• Lead Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Brief Summary

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.

Study Timeline

• Study First Submitted: 2025-05-16
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-12
• Last Update Submitted: 2025-06-12
• Study First Posted: 2025-06-22
• Last Update Posted: 2025-06-22
• Study Start: 2025-09-01
• Primary Completion: 2025-12
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Efficacy of the FLEX-AP system	4 weeks	Percentage of time spent in target sensor glucose range (70-180 mg/dL, Time in range (TIR)) during the FLEX-AP controlled ambulatory phase in Automatic mode.
Safety of the FLEX-AP system	4 weeks	To assess the safety of the FLEX-AP system in a controlled ambulatory setting simulating real-life conditions:Number of symptomatic hypoglycemia events, Number of severe hypoglycemia events, Episodes of diabetic ketoacidosis (DKA) or ketosis, Technical issues related to the insulin pump and dermatological issues related to device use.

Secondary Outcome Measures

Name	Time	Method
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.	4 weeks	7) Mean sensor glucose and glucose variability (expressed primarily as coefficient of variation and second as an SD). This outcome will be calculated for two time periods: 1) daytime (06:00 - 23:59 hours), and 2) night time (00:00 - 05:59 hours).
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)	4 weeks	This will be conducted for the unannounced and announced breakfast in the FLEX-AP controlled hospital phase, comparing with their counterparts in the Minimed 780G® controlled hospital phase. Postprandial periods assessment during the FLEX-AP controlled ambulatory phase in Automatic mode will also be conducted.
The glycemic outcome within the postprandial period will be assessed, in an exploratory analysis, the 5-h postprandial glucose incremental area under the curve.	4 weeks	This will be conducted for the unannounced and announced breakfast in the FLEX-AP controlled hospital phase, comparing with their counterparts in the Minimed 780G® controlled hospital phase. Postprandial periods assessment during the FLEX-AP controlled ambulatory phase in Automatic mode will also be conducted.
Efficacy of the FLEX-AP system	4 weeks	Number of unannounced meals during the FLEX-AP controlled ambulatory phase in Automatic mode.
To evaluate the patients perceptions	4 weeks	The patient will complete the PROMs assessment questionnaires at the end of the FLEX-AP controlled ambulatory phase in Automatic mode: System Usability Scale (SUS)

Trial Locations

Locations (1)

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Comunidad de Madrid, Spain