Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03800875
Recruitment Status : Completed
First Posted : January 11, 2019
Last Update Posted : June 8, 2021
Sponsor:
Collaborator:
Diabetes Canada
Information provided by (Responsible Party):
McGill University

Tracking Information
First Submitted Date  ICMJE June 27, 2018
First Posted Date  ICMJE January 11, 2019
Last Update Posted Date June 8, 2021
Actual Study Start Date  ICMJE February 8, 2019
Actual Primary Completion Date September 19, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2020)
Total percentage of time (22:00-22:00) that the glucose concentration remained within 3.9 and 10.0 mmol/L [ Time Frame: 24 hours ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2019)
Mean glucose level over the 24-hr period [ Time Frame: Up to 24 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2020)
  • Total percentage of time (22:00-22:00) that the glucose concentration remained within specified ranges. [ Time Frame: 24 hours ]
    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.
  • Percentage of overnight time (24:00-8:00) that the glucose concentration remained within specified ranges. [ Time Frame: 8 hours ]
    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.
  • Total amount of insulin delivered to the participant [ Time Frame: 24 hours ]
  • Mean sensor glucose concentration during the overnight stay [ Time Frame: 8 hours ]
  • Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day [ Time Frame: 27 hours ]
  • The number and severity of gastrointestinal sysmptoms experienced by a participant [ Time Frame: 27 hours ]
    GI symptoms include: nausea, vomiting, bloating and heartburn
  • Mean daytime insulin concentration [ Time Frame: 14 hours ]
  • Mean daytime concentration of amylin [ Time Frame: 14 hours ]
  • Total amount of pramlintide delivered to the participant [ Time Frame: 24 hours ]
  • Mean glucose level [ Time Frame: 24-hour period ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2019)
  • Percentage of time (22:00-22:00) of glucose levels spent: [ Time Frame: Up to 24 hours ]
    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.
  • Percentage of overnight time (24:00-8:00) of glucose levels: [ Time Frame: Up to 8 hours ]
    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.
  • Total insulin delivery measured by the closed-loop system [ Time Frame: Up to 24 hours ]
  • Mean glucose level during overnight period. [ Time Frame: Up to 8 hours ]
  • Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day [ Time Frame: Up to 27 hours ]
  • Gastrointestinal symptoms during the 27-hour closed-loop visits. [ Time Frame: Up to 27 hours ]
  • Mean daytime insulin concentration [ Time Frame: Up to 14 hours ]
  • Mean daytime glucagon concentration [ Time Frame: Up to 14 hours ]
  • Mean daytime amylin concentration [ Time Frame: Up to 14 hours ]
  • Total glucagon delivery [ Time Frame: Up to 24 hours ]
  • Total amylin delivery [ Time Frame: Up to 24 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Insulin-plus-pramlintide Closed-loop Strategy to Regulate Glucose Levels Without Carbohydrate Counting
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Experimental: Insulin-Pramlintide Closed-Loop Strategy
    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
    Intervention: Drug: 27-hour inpatient intervention
  • Active Comparator: Insulin-alone Closed Loop Strategy

    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)

    Intervention: Drug: 27-hour inpatient intervention
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 18, 2020)
24
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2019)
25
Actual Study Completion Date  ICMJE September 19, 2020
Actual Primary Completion Date September 19, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03800875
Other Study ID Numbers  ICMJE Triple Hormone
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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 de-identified. The study protocol will be available with publication.
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Responsible Party McGill University
Study Sponsor  ICMJE McGill University
Collaborators  ICMJE Diabetes Canada
Investigators  ICMJE
Principal Investigator: Michael Tsoukas McGill University Health Centre/Research Institute of the McGill University Health Centre
PRS Account McGill University
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP