A Fully-closed Loop, Pramlintide and Insulin, Artificial Pancreas Clinical Trial for Adults With Type 1 Diabetes (FCL)

A Randomized, Controlled, Crossover Pilot Trial to Assess a Fully Automated, Dual-hormone (Insulin-and-pramlintide) Artificial Pancreas Without Carbohydrate Counting in Regulating Glucose Levels in Adults With Type 1 Diabetes

The investigators aim to assess the glycemic outcomes of a fully automated insulin-and-pramlintide artificial pancreas and a comparator insulin-alone artificial pancreas with carbohydrate matched boluses.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Fiasp; Device: Artificial Pancreas; Drug: Pramlintide; Drug: Aspart

Detailed Description

The aim of this pilot study is to generate additional data of (i) a Fiasp-alone artificial pancreas with carbohydrate-matched boluses, compared to (ii) a Fiasp-plus-Pramlintide fully automated artificial pancreas with no meal announcement in an outpatient free-living setting. The study is not powered, nor aims to answer a scientific hypothesis related to the efficacy of the pramlintide and insulin closed-loop systems.

Design

The investigators will undertake a randomized crossover study to compare the following strategies:

1. Insulin-alone artificial pancreas with carbohydrate-matched boluses
2. Fiasp and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 8μg of pramlintide.

3. Fiasp and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 10μg of pramlintide.

   Each participant will be offered the opportunity to further participate in two optional additional arms:

4. Aspart and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 8μg of pramlintide.
5. Aspart and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 10μg of pramlintide.

Aspart is used in this optional arm as it is the slower-acting version of Fiasp and can therefore be used to draw reasonable comparisons. Further, Aspart is an FDA approved insulin which is commonly sold and prescribed in North America. Several co-formulations are being developed with insulin, pramlintide, and glucagon. Given the widespread adoption and use of Aspart, it makes this insulin a good candidate for use in co-formulations and an excellent option for transition to market, where they will impact many individuals living with diabetes.

Treatment period: Each intervention will last 14 hours. At-home run-ins, lasting two to four days, will occur prior to the pramlintide interventions. The interventions containing pramlintide with the same insulin will occur in sequence, one immediately after the other. The first pramlintide-and-Fiasp intervention will use a ratio of 8μg pramlintide/1unit of insulin and will be followed by the second pramlintide-and-Fiasp intervention the next day with a 10μg/1unit ratio. A similar schedule will be applied to the optional Aspart-and-pramlintide interventions. There will be a 2-29-day washout period between the Fiasp-and-pramlintide, Fiasp-alone, and Aspart-and-pramlintide interventions. Participants will be followed up remotely 1-2 days after the end of each intervention to ensure their washout period is going smoothly and will inquire about any adverse events. Remote contact can be performed via phone, email, text message or other reasonable communication channel. Participants will also be followed up remotely 1-2 days and 1-2 weeks after the end of their participation in the study.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Madison Odabassian, BSc.; Phone Number: 5142179519; Email: Madison.odabassian@mail.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3T2
      • Research Institute of the McGill University Health Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Females and males ≥ 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.
• Use of insulin pump therapy for at least 3 months.
• Effective birth-control use in individuals of childbearing potential. Individuals of child-bearing potential must agree to use a highly effective method of birth control.

Exclusion Criteria:

• Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2I (sodium-glucose transporter), GLP-1(glucagon-like peptide), Metformin, etc.).
• Current use of glucocorticoid medication (except low, stable does and inhaled steroids).
• Individuals with confirmed gastroparesis.
• Use of medication that alters gastrointestinal motility.
• Planned or ongoing pregnancy.
• Breastfeeding individuals.
• Severe hypoglycemia requiring hospitalization in the past three months.
• Severe diabetic ketoacidosis episode in the past three months.
• 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.
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fiasp-and-pramlintide fully automated system (8μg); Fiasp and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 8μg of pramlintide.	Drug: Fiasp; Fiasp Insulin delivered in a basal-bolus manner.; Device: Artificial Pancreas; Medtronic insulin pump, Dexcom G6 continuous glucose sensor, tablet running the Artificial Pancreas Algorithm.; Drug: Pramlintide; Pramlintide delivered in a basal-bolus manner.
Active Comparator: Fiasp-alone with carbohydrate-matched boluses; The Fiasp-alone intervention will have a 14 hour duration. During which, carbohydrate counting will inform insulin bolus doses based on insulin to carbohydrate ratios.	Drug: Fiasp; Fiasp Insulin delivered in a basal-bolus manner.
Experimental: Aspart-and-pramlintide fully automated system (10μg); Aspart and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 10μg of pramlintide.	Device: Artificial Pancreas; Medtronic insulin pump, Dexcom G6 continuous glucose sensor, tablet running the Artificial Pancreas Algorithm.; Drug: Pramlintide; Pramlintide delivered in a basal-bolus manner.; Drug: Aspart; Aspart insulin delivered in a basal-bolus manner.
Experimental: Fiasp-and-pramlintide fully automated system (10μg); Fiasp and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 10μg of pramlintide.	Drug: Fiasp; Fiasp Insulin delivered in a basal-bolus manner.; Device: Artificial Pancreas; Medtronic insulin pump, Dexcom G6 continuous glucose sensor, tablet running the Artificial Pancreas Algorithm.; Drug: Pramlintide; Pramlintide delivered in a basal-bolus manner.
Experimental: Aspart-and-pramlintide fully automated system (8μg); Aspart and pramlintide artificial pancreas with no meal announcement. Ratio of 1 unit of insulin for 8μg of pramlintide.	Device: Artificial Pancreas; Medtronic insulin pump, Dexcom G6 continuous glucose sensor, tablet running the Artificial Pancreas Algorithm.; Drug: Pramlintide; Pramlintide delivered in a basal-bolus manner.; Drug: Aspart; Aspart insulin delivered in a basal-bolus manner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Each participant's percentage of time glucose levels spent in the target range	Time in target range (3.9-10.0 mmol/L).	42 +/- 28 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Each participant's percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L	Glucose data will be collected from a glucose sensor and numerical glucose data will be analyzed as a function of time	42 +/- 28 hours
Each participant's percentage of time of glucose levels spent below 3.9 mmol/L	Glucose data will be collected from a glucose sensor and numerical glucose data will be analyzed as a function of time	42 +/- 28 hours
Each participant's percentage of time of glucose levels spent below 3.0 mmol/L	Glucose data will be collected from a glucose sensor and numerical glucose data will be analyzed as a function of time	42 +/- 28 hours
Each participant's percentage of time of glucose levels spent above 10.0 mmol/L	Glucose data will be collected from a glucose sensor and numerical glucose data will be analyzed as a function of time	42 +/- 28 hours
Each participant's percentage of time of glucose levels spent above 13.9 mmol/L	Glucose data will be collected from a glucose sensor and numerical glucose data will be analyzed as a function of time	42 +/- 28 hours
Each participant's percentage of time of glucose levels spent above 16.7 mmol/L	Glucose data will be collected from a glucose sensor and numerical glucose data will be analyzed as a function of time	42 +/- 28 hours
Each participant's mean glucose levels		42 +/- 28 hours
Each participant's standard deviation of glucose levels		42 +/- 28 hours
Each participant's coefficient of variance of glucose levels		42 +/- 28 hours
Total pramlintide delivery for each participant		28 +/- 28 hours
Total insulin delivery for each participant		42 +/- 28 hours
Total basal insulin delivery for each participant		42 +/- 28 hours
Total bolus insulin delivery for each participant		42 +/- 28 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Endpoints	Adverse events including gastrointestinal symptoms (nausea, vomiting, diarrhea, bloating)	42 +/- 28 hours

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Michael Tsoukas, M.D., McGill University Health Centre/Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2022
• Primary Completion (Actual): March 25, 2023
• Study Completion (Actual): March 25, 2023

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: January 6, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Insulin; Artificial Pancreas; Pramlintide; Fiasp; Aspart
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Pramlintide; Pancrelipase
• Other Study ID Numbers: 2022-8225

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes