Clinical trial NCT05205928: Weekly Subcutaneous Semaglutide as Adjunct to Closed-loop Therapy in Type 1 Diabetes Care
Official title: Weekly Subcutaneous Semaglutide as Adjunct to Closed-loop Therapy in Type 1 Diabetes Care: a Double-blind, Cross-over, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes
Diabetes Mellitus, Type 1
Keywords: Insulin
Closed-loop system
GLP-1 receptor agonist
Semaglutide
Artificial Pancreas
Diabetes Mellitus, Type 1
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2022-01-25
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* A clinical diagnosis of T1D for at least one year, as per their treating diabetes physician in agreement with the primary investigator's clinical judgment (confirmatory C-peptide and antibodies will not be required)
* Glycated hemoglobin (HbA1c) up to 11% (inclusive), performed within the last 6 months prior to study inclusion
* Insulin pump use (of any modality) for minimum 3 months
* Agreement to the use of highly effective method of birth control in persons of child-bearing age (if sexually active) and active avoidance of pregnancy during the trial. Child-bearing potential refers to participants of the female sex post-menarche and have not reached menopause or have a disclosed medical condition causing sterility (e.g. hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause.

Exclusion Criteria:

1. Current or \< 2 week use of another GLP1-receptor agonist
2. Less than 2 weeks use of any anti-hyperglycemic agent other than insulin
3. Planned or ongoing pregnancy
4. Breastfeeding individuals
5. Severe hypoglycemic episode within the last 3 months, defined as an event where glucose was \< 4 mmol/L resulting in seizure, loss of consciousness, or need to present to the emergency department
6. Severe diabetic ketoacidosis (DKA) within the last 6 months ("severe" referring to need to present to medical attention and requirement of intravenous insulin)
7. Prior history of acute pancreatitis, chronic pancreatitis, or gallbladder disease
8. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
9. Severe impairment of renal function with eGFR \<15 mL/min/1.73 m2 (using CKD-EPI formula), measured within the last 12 months
10. Clinically significant diabetic retinopathy or gastroparesis, as per the clinical judgment of the investigator
11. History of bariatric surgery within 6 months of screening
12. Any serious medical or psychiatric illness likely to interfere with study participation as per the judgment of the investigator (e.g. cirrhosis, active cancer, decompensated schizophrenia)
13. Prior adverse reaction to GLP1-RAs
14. Body mass index ≤ 21 kg/m2
15. Regular use of hydroxyurea during the expected time of Dexcom G6 use, as this medication is known to cause inaccurate measurements (43)
16. Failure to comply to the study protocol and/or research group's recommendations (e.g. change in pump parameters, ketone measurement)
17. Inability or unwillingness to comply to safe diabetes management in the view of the study group (e.g. inappropriate treatment of hypoglycemia or lack thereof)
18. Any demonstrate of difficulty in using the iMAP system following training, as per investigator's judgment
19. Concern for safety of the participant, as per the clinical judgment of the primary investigator

\*\*Note that for reasons of medicolegal protection for medical supervision, participants must be Canadian residents.\*\*

Primary outcomes:
measure: Percentage of time of plasma glucose levels spent in target range (semaglutide vs placebo)
timeFrame: 4 weeks
Secondary outcomes:
measure: Percentage of time spent in the following ranges of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: 4 weeks
measure: Percentage of time spent in the following ranges of glucose levels: below 3.9 and 3.0 mmol/L
timeFrame: 4 weeks
measure: Percentage of time spent in the following ranges of glucose levels: above 7.8, 10, and 13.9 mmol/L
timeFrame: 4 weeks
measure: Mean glucose level
timeFrame: 4 weeks
measure: Standard deviation of glucose levels as a measure of glucose variability
timeFrame: 4 weeks
measure: Percentage coefficient of variation of glucose levels
timeFrame: 4 weeks
measure: Proportion of participants with TIR between 3.9 - 10.0 mol/L ≥ 70%
timeFrame: 4 weeks
measure: Glycated hemoglobin
timeFrame: 15 weeks
measure: Average scores between interventions based on quality of life questionnaires
timeFrame: 15 weeks
measure: Blood pressure and heart rate
timeFrame: 15 weeks
measure: Measured of body mass: weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio
timeFrame: 15 weeks
measure: Lipid profile, specifically: LDL-cholesterol, HDL-cholesterol, triglycerides
timeFrame: 15 weeks
measure: Biochemical analyses (exploratory)
timeFrame: 15 weeks
measure: Urine albumin-creatinine ratio
timeFrame: 15 weeks
measure: Glucagon, C-peptide, Paracetamol absorption after mixed meal tolerance test (in first 15 participants)
timeFrame: 15 weeks
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Quebec
Study officials:
References: