Clinical trial NCT03800875: Insulin-plus-pramlintide Closed-loop Strategy to Regulate Glucose Levels Without Carbohydrate Counting
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes Mellitus, Type 1
Pramlintide
Insulin
Dual-Hormone
Closed-Loop
Artificial Pancreas
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Diabetes Canada
First posted: 2019-01-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.).

Primary outcomes:
measure: Total percentage of time (22:00-22:00) that the glucose concentration remained within 3.9 and 10.0 mmol/L
timeFrame: 24 hours
Secondary outcomes:
measure: Total percentage of time (22:00-22:00) that the glucose concentration remained within specified ranges.
timeFrame: 24 hours
measure: Percentage of overnight time (24:00-8:00) that the glucose concentration remained within specified ranges.
timeFrame: 8 hours
measure: Total amount of insulin delivered to the participant
timeFrame: 24 hours
measure: Mean sensor glucose concentration during the overnight stay
timeFrame: 8 hours
measure: Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day
timeFrame: 27 hours
measure: The number and severity of gastrointestinal sysmptoms experienced by a participant
timeFrame: 27 hours
measure: Mean daytime insulin concentration
timeFrame: 14 hours
measure: Mean daytime concentration of amylin
timeFrame: 14 hours
measure: Total amount of pramlintide delivered to the participant
timeFrame: 24 hours
measure: Mean glucose level
timeFrame: 24-hour period
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Michael Tsoukas
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsoukas MA, Majdpour D, Yale JF, Fathi AE, Garfield N, Rutkowski J, Rene J, Legault L, Haidar A. A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial. Lancet Digit Health. 2021 Nov;3(11):e723-e732. doi: 10.1016/S2589-7500(21)00139-4. Epub 2021 Sep 24.