Clinical trial NCT06387199: Alleviating Carbohydrate Counting for Patients with Type-1 Diabetes Using a Closed Loop System with Weekly Subcutaneous Semaglutide
Official title: Alleviating Carbohydrate Counting Using Weekly Subcutaneous Semaglutide Injections in People with Type 1 Diabetes on Closed-Loop Insulin Therapy: a 2x4 Factorial Randomized Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes
Diabetes Mellitus
Keywords: insulin
Closed-loop system
GLP-1 receptor agonist
Semaglutide
Diabetes mellitus, type 1
ozempic
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2024-04-26
Enrollment: 26
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: randomized placebo-controlled crossover 2x3 factorial designed trial
Primary purpose: TREATMENT

Brief summary: A closed-loop insulin system, often labelled the "artificial pancreas" (AP), consists of an insulin pump, a continuous glucose monitor, and an interface coordinating between them to regulate insulin dosage based on glucose levels. Primarily designed for managing type 1 diabetes, this system has demonstrated significant benefits in previous studies. Yet, despite these advantages, certain challenges persist.

Semaglutide, utilized in treating type 2 diabetes and obesity, is a once-weekly injectable medication that elevates levels of a gastrointestinal hormone known as Glucagon-Like Peptide-1 (GLP-1). This hormone alters gastric emptying, inhibits glucagon release, and reduces appetite. While not officially sanctioned for type 1 diabetes treatment in North America, studies have explored its efficacy as an adjunctive therapy alongside insulin, yielding favorable outcomes in blood glucose regulation. Comparable drugs like liraglutide and exenatide have been employed in type 1 diabetes treatment as well, albeit with less pronounced glucose-regulating effects compared to semaglutide, even in type 2 diabetes.

The goal of this 50-week randomized placebo-controlled crossover 2x4 factorial designed trial is to assess whether commercial automated insulin delivery (AID) systems using rapid-acting insulin with adjunct weekly injections of semaglutide (at the maximally tolerated dose) can replace carbohydrate counting with simple meal announcements (SMA) without degrading glucose control.

Detailed description: The main questions this study aims to answer are:

* Can weekly injections of semaglutide at the maximum tolerated dose in individuals with T1D on closed-loop therapy with SMA and rapid-acting insulin result in a non-inferior time spent in target range (3.9-10 mmol/L) compared to weekly placebo injections on closed-loop system with full carbohydrate counting.
* Can weekly injections of semaglutide at the maximum tolerated dose, in combination with ultra-rapid actin insulin (Lyumjev);

  1. Eliminate carbohydrate counting and any meal announcement (i.e fully closed-loop) in people with T1D on closed-loop therapy without degrading glucose control.
  2. Be more effective in substituting carbohydrate counting with SMA in people with T1D on closed-loop therapy compared with traditional rapid-acting insulin.

Participants will be asked to undergo two subsequent blinded drug interventions; one with semaglutide and the other with placebo. Both interventions include 4 meal strategies each with a 3-week duration; full carbohydrate counting with rapid-acting insulin, SMA with rapid-acting insulin, SMA with Lyumjev and fully closed-loop system with Lyumjev.

Eligibility criteria: Inclusion Criteria:

1. At least 18 years of age
2. 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)
3. Minimum 3-month use of a commercial advanced automated insulin delivery system. 4.4. Agreement to use an effective method of birth control for individuals with child-bearing potential. Child-bearing potential refers to participants of the female sex post-menarche who have not reached menopause and who do not have a 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. Use of GLP1-RAs within the last 4 weeks.
2. Use of any anti-hyperglycemic agent other than insulin within the last 2 weeks.
3. Planned or ongoing pregnancy
4. Breastfeeding
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 \<30 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. Bariatric surgery within the last 6 months.
12. A serious medical or psychiatric illness that is likely to interfere with study participation as per the judgment of the investigator (e.g. cirrhosis, active cancer, decompensated schizophrenia).
13. Body mass index ≤ 21 kg/m2
14. 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)
15. Concern for safety of the participant, as per the clinical judgment of the primary investigator

Primary outcomes:
measure: Percentage of daytime plasma glucose levels spent in target range (semaglutide vs. placebo)
timeFrame: 24 weeks
Secondary outcomes:
measure: Percentage of time spent in the range of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: 24 weeks
measure: Percentage of time spent in glucose levels below 3.9 and 3.0 mmol/L
timeFrame: 24 weeks
measure: Percentage of time spent in glucose levels above 7.8, 10 and 13.9 mmol/L
timeFrame: 24 weeks
measure: Mean glucose level
timeFrame: 24 weeks
measure: Standard deviation of glucose levels as a measure of glucose variability
timeFrame: 24 weeks
measure: Percentage coefficient of variation of glucose levels
timeFrame: 24 weeks
measure: Proportions of participants with time in range between 3.9 - 10.0 mmol/L≥ 70%
timeFrame: 24 weeks
measure: Glycated hemoglobin (HbA1c)
timeFrame: 24 weeks
measure: Area under the curve 0-2h post meal, 0-3h post peal
timeFrame: 24 weeks
measure: Average scores between interventions on the Type 1 Diabetes Distress Scale questionnaire
timeFrame: 24 weeks
measure: Average scores between interventions on the Diabetes Treatment Satisfaction questionnaire
timeFrame: 24 weeks
measure: Average scores between interventions based on the Hypoglycemic Fear Survey - II
timeFrame: 24 weeks
measure: Heart rate
timeFrame: 24 weeks
measure: Blood pressure
timeFrame: 24 weeks
measure: Measure of body weight
timeFrame: 24 weeks
measure: Measure of body mass index
timeFrame: 24 weeks
measure: Measure of waist circumference and hip circumference
timeFrame: 24 weeks
measure: Measure of waist-to-hip ratio
timeFrame: 24 weeks
measure: Lipid profile, specifically: LDL-cholesterol, HDL-cholesterol, triglycerides
timeFrame: 24 weeks
measure: Urine albumin-creatinine ratio
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Quebec
Study officials:
References: