Insulin-plus-pramlintide Closed-loop Strategy to Regulate Glucose Levels Without Carbohydrate Counting

Diabetes Mellitus, Type 1 Clinical Trial

— Dual  

Official title:

A Randomized, Controlled, Crossover Trial to Assess a Dual-hormone (Insulin-pramlintide) Closed-loop Delivery Without Carbohydrate Counting in Regulating Glucose Levels in Adults With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03800875
• Other study ID #: Triple Hormone
• Status: Completed
• Phase: Phase 2
• Start date: February 8, 2019
• Est. completion date: September 19, 2020

Study information

• Verified date: June 2021
• Source: McGill University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Closed-loop system systems that are shown to alleviate the burden of carbohydrate counting without degrading glucose control are still lacking. In this proposal, the investigators aim to develop a novel, fully-automated, closed-loop system that delivers insulin and pramlintide that controls postprandial glucose levels without any input from the user.

Description:

Meal carbohydrate content is the main determinant of prandial insulin needs, and consequently, accurate carbohydrate counting is recommended for type 1 diabetes. Advances in glucose sensors have motivated the development of the closed-loop system to automatically regulate glucose levels in individuals with type 1 diabetes. In the closed-loop system, a dosing algorithm adjusts the pump insulin infusion rate based on continuous glucose sensor readings. Closed-loop system systems that are shown to alleviate the burden of carbohydrate counting without degrading glucose control are still lacking. In this proposal, the investigators aim to develop a novel, fully-automated, closed-loop system that delivers insulin and pramlintide that controls postprandial glucose levels without any input from the user. Thus, the two hormones' role in the postprandial state will be as follows: 1. Insulin: to reduce plasma glucose levels. Insulin delivery needs to be aggressive to counter-act fast increase in post-meal glucose levels. 2. Pramlintide: to slow gastric emptying and aim insulin in efficiently controlling postprandial glucose levels. The aim of this study is to assess a fully automated, dual-hormone, closed-loop system that delivers insulin, and pramlintide to control glucose levels without degrading overall glycemic control compared to an insulin-alone closed-loop system with carbohydrate-matched boluses. The investigators hypothesize that the dual-hormone closed-loop system will alleviate carbohydrate-counting burden (fully reactive system) without degrading glucose control compared to the insulin-alone closed-loop system.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 19, 2020
• Est. primary completion date: September 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males and females = 18 years of age.

2. Clinical diagnosis of type 1 diabetes for at least 12 months. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.

3. Insulin pump therapy for at least 6 months.

4. HbA1c = 12% in the last 6 months.

Exclusion Criteria:

1. Current or = 1 month use of other antihyperglycemic agents (SGLT2, GLP-1, Metformin, Acarbose, etc.…).

2. Severe hypoglycemic episode within one month of admission.

3. Severe diabetic ketoacidosis episode within one month of admission.

4. Pregnancy.

5. Known or suspected allergy to the study drugs.

6. Gastroparesis.

7. Use of prokinetic drugs that stimulate gastric emptying (domperidone, cisapride, metoclopramide).

8. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.

9. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.

10. Current use of glucocorticoid medication.

11. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

12. Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• 27-hour inpatient intervention
Subjects will be admitted at the research facility at 19:00. Each 27-hour intervention visit includes 3 standardized meals (8:00, 12:00, and 17:00), an evening snack (22:00) and an overnight stay. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The infusion rate of either insulin alone or insulin and pramlintide will be changed manually based on the computer generated recommendation. The computer generated recommendations are based on a predictive algorithm.

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
McGill University	Diabetes Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total percentage of time (22:00-22:00) that the glucose concentration remained within 3.9 and 10.0 mmol/L		24 hours
Secondary	Total percentage of time (22:00-22:00) that the glucose concentration remained within specified ranges.	a. between 3.9 and 7.8 mmol/L; b. below 3.9 mmol/L; c. between 3.9 and 10 mmol/L d. below 3.3 mmol/L; e. below 2.8 mmol/L; f. above 7.8 mmol/L; g. above 10 mmol/L; h. above 13.9 mmol/L; i. above 16.7 mmol/L.	24 hours
Secondary	Percentage of overnight time (24:00-8:00) that the glucose concentration remained within specified ranges.	a. between 3.9 and 7.8 mmol/L; b. between 3.9 and 10 mmol/L; c. below 3.9 mmol/L; d. below 3.3 mmol/L; e. below 2.8 mmol/L; f. above 7.8 mmol/L; g. above 10 mmol/L; h. above 13.9 mmol/L; i. above 16.7 mmol/L.	8 hours
Secondary	Total amount of insulin delivered to the participant		24 hours
Secondary	Mean sensor glucose concentration during the overnight stay		8 hours
Secondary	Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day		27 hours
Secondary	The number and severity of gastrointestinal sysmptoms experienced by a participant	GI symptoms include: nausea, vomiting, bloating and heartburn	27 hours
Secondary	Mean daytime insulin concentration		14 hours
Secondary	Mean daytime concentration of amylin		14 hours
Secondary	Total amount of pramlintide delivered to the participant		24 hours
Secondary	Mean glucose level		24-hour period