Artificial Pancreas With Carbohydrate Suggestion for Patients With Type 1 Diabetes Prone to Hypoglycemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05628662
Recruitment Status : Completed
First Posted : November 29, 2022
Last Update Posted : November 29, 2022
Sponsor:
Collaborators:
Universitat Politècnica de València
Universitat de Girona
Information provided by (Responsible Party):
Ignacio Conget, Hospital Clinic of Barcelona

Brief Summary:

Achieving near-normoglycemia has been established as the main objective for most patients with Type 1 Diabetes (T1D). Automated insulin delivery (AID) systems, the so-called artificial pancreas (AP) or closed-loop systems, may represent the ideal solution, especially for patients not reaching the therapeutic goals with multiples doses of insulin or open-loop delivery systems. Despite the advances in recent years that have proven the efficacy and safety of these devices in clinical trials and clinical practice settings, such evidence cannot be extrapolated to highly unstable patients, as problematic hypoglycemia remains an exclusion criterion in most of the trials.

The SAFE-AP system is a single-hormone hybrid closed-loop controller based on a proportional derivative with an insulin feedback controller that integrates a safety layer with insulin-on-board constraints and sliding mode reference conditioning. The hybrid closed-loop system includes a second safety feedback loop with a controller that triggers carbohydrate recommendations to the patient. Both control loops are coordinated to ensure that the counter-regulatory effect of rescue carbohydrates is not counteracted with insulin. Such system has been previously proven effective in unannounced exercise, one of the main challenges in AID systems development. Additionally, the algorithm has been recently tailored to achieve a better control in the subgroup of T1D patients prone to hypoglycemia.

In this project, a rigorous clinical testing of the SAFE-AP system will be carried out in 12 patients with T1D and problematic hypoglycemia, despite treatment with continuous subcutaneous insulin infusion. The safety and performance of the system will be evaluated in a 32-hour pilot study, including 4 meals, one overnight period and 2 unannounced aerobic exercise sessions. The study will be performed in a hospital setting with the on-site supervision of a specialized nurse and a diabetologist, as well as an engineer in remote control.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Prone to Hypoglycemia Device: Automated Insulin Delivery System (SAFE-AP) Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study Evaluating the Safety and Performance of an Artificial Pancreas With Carbohydrate Suggestion for Patients With Type 1 Diabetes Prone to Hypoglycemia
Actual Study Start Date : October 22, 2021
Actual Primary Completion Date : April 6, 2022
Actual Study Completion Date : April 6, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Automated Insulin Delivery System (SAFE-AP)
Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration. Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the software under investigation (SAFE-AP) based on blood glucose estimations from CGM.
Device: Automated Insulin Delivery System (SAFE-AP)
Each subject will undergo a 32-hour in-hospital study, including 4 meals (60 grams of carbohydrates each, except 50 grams for breakfast), one overnight period and 2 unannounced aerobic exercise sessions. Each exercise session consists of three 15-minute sets on a cycle ergometer at 70% of maximum heart rate with 5 minutes of rest between sets.




Primary Outcome Measures :
  1. Percentage of CGM time in glucose range 70-180 mg/dl during the study. [ Time Frame: From 12 AM of the first day of study until 4 PM of the second day of study ]

Secondary Outcome Measures :
  1. Percentage of CGM time in glucose range 70-180 mg/dl during nighttime [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
  2. Percentage of CGM time in glucose range 70-180 mg/dl during exercise and recovery [ Time Frame: Defined as 3 hours after exercise initiation ]
  3. Percentage of CGM time in glucose range 70-180 mg/dl during postprandial period [ Time Frame: Defined as 4 hours since mealtime ]
  4. Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during the study [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
  5. Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during nighttime [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
  6. Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during exercise and recovery [ Time Frame: Defined as 3 hours after exercise initiation ]
  7. Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during postprandial period [ Time Frame: Defined as 4 hours since mealtime ]
  8. Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during the study [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
  9. Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during nighttime [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
  10. Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during exercise and recovery [ Time Frame: Defined as 3 hours after exercise initiation ]
  11. Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during postprandial period [ Time Frame: Defined as 4 hours since mealtime ]
  12. Glucose coefficient of variation during the study [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
  13. Number of hypoglycemic events [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
    Defined as sensor glucose <70 mg/dL during 15 minutes or symptomatic hypoglycemia confirmed with plasma glucose

  14. Number of carbohydrate rescue events during the study [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
  15. Number of acute metabolic events during the study [ Time Frame: From 22 PM of the first day of study until 7 AM of the second day of study ]
    Defined as severe hypoglycemia and diabetic ketoacidosis



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects aged 18 or more with Type 1 Diabetes for at least 5 years.
  • Treated with continuous subcutaneous insulin infusion (CSII) for at least six months.
  • Trained to carbohydrate counting.
  • Subjects prone to hypoglycemia, despite optimal diabetes management and hypoglycemia-specific education programs, as defined by >4 hypoglycemic episodes per week and at least one of the following:

    1. Occurrence of at least 2 severe hypoglycemic episodes during the last 2 years (need for third party).
    2. Occurrence of at least 1 severe hypoglycemic episode during the last 2 years and high glycemic variability (coefficient of variation >36%).
    3. Impaired awareness of hypoglycemia (Clarke test ≥4).
  • Physical examination, laboratory data and EKG without alterations. Abnormalities considered clinically irrelevant by the investigator will not be exclusion criteria.
  • Negative SARS-CoV-2 PCR test performed at arrival.
  • Subject willing to wear the SAFE-AP system continuously throughout the study.

Exclusion Criteria:

  • Pregnancy and breastfeeding.
  • History of drug or alcohol abuse.
  • Progressive fatal disease.
  • Clinically relevant microvascular complications (macroalbuminuria, pre-proliferative and proliferative retinopathy), cardiovascular, hepatic, neurological, endocrine or other systematic, apart from T1D, which may hamper the implementation of the clinical study protocol or interpretation of results study.
  • Scheduled surgery during the study period.
  • Mental conditions that prevent the subject to understand the nature, purpose and possible consequences of the study.
  • Subjects who are unlikely to meet the clinical study protocol, eg. uncooperative attitude, inability to return for follow-up visits, or poor probability of completing the study.
  • Using an experimental drug or device during the past 30 days.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05628662


Locations
Layout table for location information
Spain
Hospital Clínic de Barcelona
Barcelona, Spain, 08036
Sponsors and Collaborators
Hospital Clinic of Barcelona
Universitat Politècnica de València
Universitat de Girona
Investigators
Layout table for investigator information
Study Director: Jorge Bondia, PhD Universitat Politècnica de València
Study Director: Josep Vehí, PhD Universitat de Girona
Study Director: Ignacio Conget, MD PhD Hospital Clinic of Barcelona
Study Chair: Marga Giménez, MD PhD Hospital Clinic of Barcelona
Publications:
Layout table for additonal information
Responsible Party: Ignacio Conget, Head of Endocrinology and Nutrition Department, Principal Investigator, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT05628662    
Other Study ID Numbers: HEAP
First Posted: November 29, 2022    Key Record Dates
Last Update Posted: November 29, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ignacio Conget, Hospital Clinic of Barcelona:
Type 1 Diabetes
Hypoglycemia
Artificial Pancreas
Closed-loop
Automated insulin delivery
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs