Alleviating Carbohydrate Counting for Patients With Type 1 Diabetes Using a Novel Insulin-plus-pramlintide Artificial Pancreas

Alleviating Carbohydrate Counting for Patients With Type 1 Diabetes Using a Novel Insulin-plus-pramlintide Artificial Pancreas: a Randomized Controlled Crossover Trial.

One of the main challenges in maintaining tight glucose control in a closed-loop system occurs at meal times. Amylin is a gluco-regulatory beta-cell hormone that is co-secreted with insulin in response to nutrient stimuli, and is deficient in patients with type 1 diabetes. Amylin, in the postprandial period, contributes to regulating glucose levels by delaying gastric emptying, suppressing nutrient-stimulated glucagon secretion, and increasing satiety. Pramlintide is a synthetic analog of the hormone amylin. A closed-loop system that delivers both insulin and pramlintide, based on glucose sensor readings, has the potential to better normalize glucose levels, especially during the post-prandial period.

The aim of this project is to assess whether co-administration of pramlintide with the improved insulin aspart formulation - Fiasp, in an artificial pancreas system, will alleviate the need for carb counting by replacing it with a simple meal announcement, without degrading the quality of glycemic control in a closed-loop therapy.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes; Type 1 Diabetes Mellitus; Hyperglycemia, Postprandial
• Intervention / Treatment: Drug: Fiasp; Drug: Placebo; Device: Artificial Pancreas; Drug: Pramlintide Acetate

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B1
      • 3555 University Street

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed and dated written informed consent
2. Males and females ≥ 12 years of age
3. HbA1c ≤ 12%
4. Insulin pump use for at least 3 months
5. Clinical diagnosis with type 1 diabetes for at least 12 months. The diagnosis of T1D is based on the investigator's clinical judgment; C peptide level and antibody determinations are not planned.
6. Women of child-bearing potential must be ready and able to use a highly effective method of birth control. Women of childbearing potential are females who have experienced [the first occurrence of menstruation] and do not meet the criteria for women not of childbearing potential. Women not of childbearing potential are females who are permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.

Exclusion Criteria:

Participants who meet any of the following criteria are not eligible for the study:

1. Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2 inhibitors, GLP-1 agonists, Metformin, Acarbose, etc.…).
2. Current use of glucocorticoid medication.
3. Use of medication that alters gastrointestinal motility.
4. Planned or ongoing pregnancy.
5. Breastfeeding individuals.
6. Severe hypoglycemic episode within one month of admission.
7. Severe diabetes ketoacidosis episode within one month of admission.
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. Known hypersensitivity to any of the study drugs or their excipients.
11. Individuals with confirmed gastroparesis.
12. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
13. Unable to travel to research center within 3h if needed during study interventions
14. Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).

Study Discontinuation/Withdrawal

1. Failure to comply with the protocol.
2. Pregnancy.
3. After an event which the PI believes it is not in the best interest for the patient to continue the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fiasp-plus-Placebo with Full Carbohydrate Counting; Fiasp insulin and placebo insulin infusion in two insulin pumps with full carbohydrate counting.	Drug: Fiasp; Fiasp Insulin delivered in a basal-bolus manner.; Drug: Placebo; Placebo delivered in a basal-bolus manner with a fixed ratio with insulin.; Device: Artificial Pancreas; Tandem insulin pump, dexcom G5 sensor, Nexus 5 cellphone running the iMAP algorithm.
Placebo Comparator: Fiasp-plus-placebo with Simple Meal Announcement; Fiasp insulin and placebo (saline) insulin infusion in two insulin pumps using the simple meal announcement system.	Drug: Fiasp; Fiasp Insulin delivered in a basal-bolus manner.; Drug: Placebo; Placebo delivered in a basal-bolus manner with a fixed ratio with insulin.; Device: Artificial Pancreas; Tandem insulin pump, dexcom G5 sensor, Nexus 5 cellphone running the iMAP algorithm.
Active Comparator: Fiasp-plus-Pramlintide with Simple Meal Announcement; Fiasp insulin and pramlintide insulin infusion in two insulin pumps using the simple meal announcement system.	Drug: Fiasp; Fiasp Insulin delivered in a basal-bolus manner.; Device: Artificial Pancreas; Tandem insulin pump, dexcom G5 sensor, Nexus 5 cellphone running the iMAP algorithm.; Drug: Pramlintide Acetate; Pramlintide delivered in a basal-bolus manner with a fixed ratio with insulin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Each participant's time in target range	Time in target range (3.9-10mmol/L)	12 days
Mean score of the Emotional Burden section of the Diabetes Distress Scale	Average of all question's scores (from 1-6). Higher score means more emotional burden.	12 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Each participant's percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L	12 days
Each participant's percentage of time of glucose levels spent between 3.9 and 10 mmol/L	12 days
Each participant's percentage of time of glucose levels spent below 3.9, 3.3, and 2.8 mmol/L	12 days
Each participant's percentage of time of glucose levels spent above 7.8, 10, 13.9 and 16.7 mmol/L	12 days
Each participant's mean glucose level	12 days
Each participant's standard deviation of glucose levels as a measure of glucose variability	12 days
Each participant's number of hypoglycemia events defined as at least 15 min below 3.0 mmol/L	12 days
Each participant's number of Gastrointestinal symptoms	12 days
Each participant's total insulin delivery	12 days

Collaborators and Investigators

• Sponsor: McGill University
• Collaborators: Juvenile Diabetes Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2020
• Primary Completion (Actual): January 30, 2022
• Study Completion (Actual): January 30, 2022

Study Registration Dates

• First Submitted: August 26, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: artificial pancreas; closed-loop; type 1 diabetes; hyperglycemia; pramlintide; fiasp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Pramlintide; Pancrelipase
• Other Study ID Numbers: 2020-5712

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The raw data (i.e., insulin delivery, glucose levels, individual participant data) and informed consent form could be shared by the corresponding author, ahmad.haidar@mcgill.ca, upon reasonable request for academic purposes, subject to Material Transfer Agreement and approval of McGill University Health Center's Research Ethics Board. All data shared will be deidentified. Study protocol is available with publication.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

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