- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03800875
Insulin-plus-pramlintide Closed-loop Strategy to Regulate Glucose Levels Without Carbohydrate Counting (Dual)
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 Overview
Status
Conditions
Intervention / Treatment
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:
- Insulin: to reduce plasma glucose levels. Insulin delivery needs to be aggressive to counter-act fast increase in post-meal glucose levels.
- 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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Quebec
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Montréal, Quebec, Canada, H4A 3J1
- McGill University Health Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
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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.
|
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) |
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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24 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
24 hours
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Percentage of overnight time (24:00-8:00) that the glucose concentration remained within specified ranges.
Time Frame: 8 hours
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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.
|
8 hours
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Total amount of insulin delivered to the participant
Time Frame: 24 hours
|
24 hours
|
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Mean sensor glucose concentration during the overnight stay
Time Frame: 8 hours
|
8 hours
|
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Number of participants experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night; c. the day
Time Frame: 27 hours
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27 hours
|
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The number and severity of gastrointestinal sysmptoms experienced by a participant
Time Frame: 27 hours
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GI symptoms include: nausea, vomiting, bloating and heartburn
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27 hours
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Mean daytime insulin concentration
Time Frame: 14 hours
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14 hours
|
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Mean daytime concentration of amylin
Time Frame: 14 hours
|
14 hours
|
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Total amount of pramlintide delivered to the participant
Time Frame: 24 hours
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24 hours
|
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Mean glucose level
Time Frame: 24-hour period
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24-hour period
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Tsoukas, McGill University Health Centre/Research Institute of the McGill University Health Centre
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Triple Hormone
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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