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

NCT03800875 | Completed Phase 2

• 1 other identifier: Triple Hormone
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1; Pramlintide; Insulin; Dual-Hormone; Closed-Loop; Artificial Pancreas

Outcome Measures

Primary Outcomes (1)

• Total percentage of time (22:00-22:00) that the glucose concentration remained within 3.9 and 10.0 mmol/L

  24 hours

Secondary Outcomes (10)

• Total percentage of time (22:00-22:00) that the glucose concentration remained within specified ranges.

  24 hours

• Percentage of overnight time (24:00-8:00) that the glucose concentration remained within specified ranges.

  8 hours

• Total amount of insulin delivered to the participant

  24 hours

• Mean sensor glucose concentration during the overnight stay

  8 hours

• Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day

  27 hours

Study Arms (2)

Insulin-Pramlintide Closed-Loop Strategy

EXPERIMENTAL

Fast-acting insulin will be delivered using two separate infusion pumps. The pumps' infusion rates will then be changed manually based on the computer-generated recommendation. The computer-generated recommendations are based on a dosing algorithm. With no-meal announcement or carbohydrate counting, the dual-hormone closed-loop system will be fully reactive, and insulin and pramlintide dosages will be based solely on sensor readings

Drug: 27-hour inpatient intervention

Insulin-alone Closed Loop Strategy

ACTIVE COMPARATOR

Fast-acting insulin will be delivered by a subcutaneous insulin infusion pump based on an algorithm that automatically adjusts insulin rates based on a dosing algorithm. The carbohydrate content for every ingested meal will be entered into the algorithm to calculate the insulin prandial bolus based on each participant's insulin-to-carbohydrate ratio. The carbohydrate content will be entered at the onset of the meal. Drug(s): Insulin (FiAsp)

Drug: 27-hour inpatient intervention

Interventions

27-hour inpatient intervention DRUG

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.

Insulin-Pramlintide Closed-Loop Strategy; Insulin-alone Closed Loop Strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 18 years of age.
• 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.
• Insulin pump therapy for at least 6 months.
• HbA1c ≤ 12% in the last 6 months.

You may not qualify if:

• Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2, GLP-1, Metformin, Acarbose, etc.…).
• Severe hypoglycemic episode within one month of admission.
• Severe diabetic ketoacidosis episode within one month of admission.
• Pregnancy.
• Known or suspected allergy to the study drugs.
• Gastroparesis.
• Use of prokinetic drugs that stimulate gastric emptying (domperidone, cisapride, metoclopramide).
• Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
• Recent (\< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• Current use of glucocorticoid medication.
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
• Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).

Sponsors & Collaborators

• McGill University: lead
• Diabetes Canada: collaborator

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (1)

• 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.

  PMID: 34580055 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Study Officials

• Michael Tsoukas

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: January 11, 2019
• Study Start: February 8, 2019
• Primary Completion: September 19, 2020
• Study Completion: September 19, 2020
• Last Updated: June 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

CA (1)