Validation of a Biomathematical Model to Help Identify the Parameters of Flexible Insulin Therapy (ModIF)

Validation of a Biomathematical Model to Help Identify the Parameters of Flexible Insulin Therapy: Monocentric, Controlled, Randomized and Prospective Pilot Clinical Study in Patients With Type 1 Diabetes.

Type 1 diabetes is an autoimmune disease that requires daily treatment with insulin. The use of subcutaneous pumps for continuous insulin delivery has been an important advance for diabetic patients. The evolution of technologies through the miniaturization of insulin pumps and the advent of continuous glucose sensors has made it possible to understand the development of the artificial pancreas. Several teams are working on the development of an artificial pancreas with considerable progress in closed-loop insulin delivery, particularly during the night.

The Laboratory of Digital Sciences of Nantes has developed a new bio-mathematical model describing the glucose-insulin dynamics, closer to the physiological reality of patients with type 1 diabetes. This model allows firstly to identify the parameters of flexible insulin therapy (basal rate, insulin sensitivity, carbohydrate ratios).

The objective of this study is to test the relevance of this bio-mathematical model to help the physician identify the parameters of flexible insulin therapy (basal rate, insulin sensitivity, carbohydrate ratios).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Bio-mathematical model; Other: Without bio-mathematical model

Detailed Description

This is an open randomized pilot clinical study, comparing the effectiveness of medical decision assisted by this bio-mathematical model ("augmented physician") versus unassisted medical decision, to define the parameters of flexible insulin therapy based on data from a continuous glucose measurement record for 7 days.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient with type 1 diabetes for at least two years with an indication for sensor placement,
2. Patient patient with at least 6 months of external insulin pump therapy and using the Medtronic 640G pump with or without the Enlite® System.
3. Patient having at least 6 months experience of flexible insulin therapy,
4. Patient with HbA1c <10% (less than 4 months' duration of testing in a medical laboratory or equivalent),
5. Patient who has been wearing a Continuous Glucose Monitoring device for at least 3 months,
6. Adult patient,
7. Patient affiliated to a Social Security or equivalent,
8. Patient who has signed Informed Consent Form.

Exclusion Criteria:

1. Patient with type 2 diabetes or secondary diabetes
2. Patient with any serious medical condition that may affect participation in the study,
3. Patient benefiting from a legal protection measure,
4. Woman who is pregnant or likely to become pregnant during the course of the study, i.e., a lack of effective contraception in women of childbearing age,
5. Breastfeeding,
6. Psychological and/or physical condition that may affect the proper monitoring of study procedures,
7. Severe hypoglycemia leading to convulsions or loss of consciousness within the last 12 months,
8. Decreased hypoglycemic feelings (as judged by the clinician),
9. Impaired renal function (creatinine clearance calculated by CKD-EPI < 30mL/min),
10. Patient who has had a pancreas transplant or pancreatic islets,
11. Persons with severe uncorrected hearing and/or visual acuity problems,
12. Insulin resistance defined by daily insulin requirements > 1 U/kg/day in the week prior to inclusion,
13. Patient treated with oral corticosteroid therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Augmented physician; Medical decision assisted by the bio-mathematical model to define the parameters of flexible insulin therapy based on data from a continuous glucose measurement record.	Other: Bio-mathematical model; bio-mathematical model to help the physician identify the parameters of flexible insulin therapy (basal rate, insulin sensitivity, carbohydrate ratios)
Placebo Comparator: Control; Unassisted medical decision to define the parameters of flexible insulin therapy based on data from a continuous glucose measurement record.	Other: Without bio-mathematical model; No bio-mathematical model to help the physician identify the parameters of flexible insulin therapy (basal rate, insulin sensitivity, carbohydrate ratios)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of time in glycemic target	percentage of time in glycemic target (70-180 mg/dL) during the four weeks following medical consultation where the parameters of flexible insulin therapy are estimated by the physician, either conventionally or with the help of the bio-mathematical model, and parameterized in the insulin pump.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coefficient of variation of glucose	Hypoglycemic readings < 0.7 g/L, Time below 0.7 g/L, Time above 1.8 g/L	75 days
Frequency of severe hypoglycemia	Frequency of severe hypoglycemia (requiring the intervention of a third party)	75 days
Robustness of the model	for each glycemic holter, identification of the model from the first 3 days of recording and comparison during the last 3 days of the predicted results with the observed glucose levels. And comparison, in the "delayed modelling" arm, of the doses estimated by the diabetologist and the doses estimated from the model.	75 days
assessment of patient compliance	evaluation of the difference between the theoretical doses recommended following modelling and the actual doses given by the patient	75 days
assessment of patient acceptance	Quality of life questionnaire SF36	75 days
the average time of medical consultation in each group.	Duration of the consultation	75 days
changes in heart rate over time		75 days
changes in activity over time		75 days

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Lucy CHAILLOUS, Dr, CHU de Nantes

Publications and helpful links

General Publications

• Scharbarg E, Greck J, Le Carpentier E, Chaillous L, Moog CH. A metamodel-based flexible insulin therapy for type 1 diabetes patients subjected to aerobic physical activity. Sci Rep. 2022 May 16;12(1):8017. doi: 10.1038/s41598-022-11772-x.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Actual): October 4, 2022
• Study Completion (Actual): October 4, 2022

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Type 1 diabetes mellitus; biomathematical model; Flexible insulin therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: RC20_0278

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No