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A closed-loop insulin system, also referred to as the "artificial pancreas" (AP), is made up of an insulin pump, a continuous glucose monitor, and an application communicating between the two to adjust insulin administration based on glucose control. This is meant for the treatment of type 1 diabetes. The McGill Artificial Pancreas (MAP) has been used previously in type 1 diabetes with significant benefits. Though prior studies have shown significant benefit with this system, some challenges still exist.
Semaglutide is used in type 2 diabetes and obesity; it is a once-weekly injectable medication that increases levels of a gut hormone called Glucagon-Like Peptide-1, which modifies gastric emptying, suppresses glucagon, and suppresses appetite. Though its use is not approved in type 1 diabetes in North America, it (along with similar drugs) has been used in studies as adjunctive therapy with insulin with benefits on blood sugar control. Similar medications have been used in type 1 diabetes (such as liraglutide and exenatide), but are not as strong in glucose effect even in type 2 diabetes as compared with semaglutide.
The purpose of our study is to see if semaglutide administered weekly at the maximum tolerated dose in those with type 1 diabetes will have improved glucose control (as per time in target range from continuous glucose monitoring data) compared to placebo, while using a closed-loop insulin system.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo + closed-loop insulin system | Active Comparator |
| |
| Semaglutide, Ozempic® (at maximum tolerated dose) + closed-loop insulin system | Experimental | Semaglutide is a Glucagon-Like Peptide 1 Receptor Agonist. It stimulates GLP1 in the body, which allows for increased satiety, reduced glucagon levels, delayed gastric emptying, and in some, increased insulin secretion. It is a once per week subcutaneous injection. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Outpatient therapy: 11 weeks of drug therapy with usual treatment + 4 weeks of closed-loop therapy | Drug | The blinded drug will be used with participant's routine therapy (+ continuous glucose monitoring if not already in use) for 11 weeks with follow-up from qualified research personnel concerning pump settings, side effects, and incremental dose increase. While continuing to use the medication, there are 4 weeks of closed-loop pump therapy and drug use; glycemic outcomes will be taken from the last 4 weeks. This will be followed by laboratory and anthropometric testing, followed by 2 weeks of wash-out. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of time of plasma glucose levels spent in target range (semaglutide vs placebo) | Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs semaglutide (at maximal tolerated dose) on closed-loop insulin system. | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of time spent in the following ranges of glucose levels between 3.9 and 7.8 mmol/L | % as per CGM data | 4 weeks |
| Percentage of time spent in the following ranges of glucose levels: below 3.9 and 3.0 mmol/L |
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Inclusion Criteria:
Exclusion Criteria:
**Note that for reasons of medicolegal protection for medical supervision, participants must be Canadian residents.**
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Institute of the McGill University Health Centre | Montreal | Quebec | H4A 3J1 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39794615 | Derived | Pasqua MR, Tsoukas MA, Kobayati A, Aboznadah W, Jafar A, Haidar A. Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: a double-blind, randomized, crossover trial. Nat Med. 2025 Apr;31(4):1239-1245. doi: 10.1038/s41591-024-03463-z. Epub 2025 Jan 10. |
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Protocol will be included upon finalization onto the website, as well as upon request.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 6, 2022 |
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|
% as per CGM data
| 4 weeks |
| Percentage of time spent in the following ranges of glucose levels: above 7.8, 10, and 13.9 mmol/L | % as per CGM data | 4 weeks |
| Mean glucose level | Defined as per CGM data, in mmol/L | 4 weeks |
| Standard deviation of glucose levels as a measure of glucose variability | Defined as per CGM data, in mmol/L | 4 weeks |
| Percentage coefficient of variation of glucose levels | % as per CGM data | 4 weeks |
| Proportion of participants with TIR between 3.9 - 10.0 mol/L ≥ 70% | As per CGM data | 4 weeks |
| Glycated hemoglobin | Blood test to assess control within last 3-4 months | 15 weeks |
| Average scores between interventions based on quality of life questionnaires | These include: Type 1 Diabetes Distress Scale, Hypoglycemic Fear Survey - II, INSPIRE questionnaire for adults, Diabetes Bowel Syndrome Questionnaire, Diabetes Treatment Satisfaction Questionnaire | 15 weeks |
| Blood pressure and heart rate | Body measurements as described (mmHg and beats per minutes) | 15 weeks |
| Measured of body mass: weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio | Measurements done at visit - weight in kilograms, body mass index as per kg/m^2, circumferences in cm | 15 weeks |
| Lipid profile, specifically: LDL-cholesterol, HDL-cholesterol, triglycerides | Blood tests, in mmol/L | 15 weeks |
| Biochemical analyses (exploratory) | CRP, ferritin, IL-6, Brain natriuretic peptide, TXNIP | 15 weeks |
| Urine albumin-creatinine ratio | Urine test | 15 weeks |
| Glucagon, C-peptide, Paracetamol absorption after mixed meal tolerance test (in first 15 participants) | Test done where beverage given and subsequent blood tests done after. | 15 weeks |
| Apr 2, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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