Alleviating Carbohydrate Counting for Patients with Type-1 Diabetes Using a Closed Loop System with Weekly Subcutaneous Semaglutide

NCT06387199 | Recruiting Phase 2 DMC

• 1 other identifier: 2024-10227
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes; Diabetes Mellitus

Keywords

insulin; Closed-loop system; GLP-1 receptor agonist; Semaglutide; Diabetes mellitus, type 1; ozempic

Outcome Measures

Primary Outcomes (1)

• Percentage of daytime 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 plasma glucose for placebo vs semaglutide (at maximal tolerated dose) on closed-loop insulin therapy

  24 weeks

Secondary Outcomes (20)

• Percentage of time spent in the range of glucose levels between 3.9 and 7.8 mmol/L

  24 weeks

• Percentage of time spent in glucose levels below 3.9 and 3.0 mmol/L

  24 weeks

• Percentage of time spent in glucose levels above 7.8, 10 and 13.9 mmol/L

  24 weeks

• Mean glucose level

  24 weeks

• Standard deviation of glucose levels as a measure of glucose variability

  24 weeks

Study Arms (2)

Weekly placebo injections on regular closed-loop insulin pump therapy

ACTIVE COMPARATOR

Drug: Placebo with 4 meal strategies

Weekly semaglutide (Ozempic®) injections on regular closed-loop insulin pump therapy

EXPERIMENTAL

Semaglutide is a Glucagon-like peptide 1 (GLP-1) receptor agonist. It up regulates GLP-1, which reduces glucagon levels, increases satiety and - in some particular cases - increases insulin production. It will be subcutaneously injected weekly by participants at progressively increasing doses. Once the maximum tolerated dose is achieved, participants will begin the meal strategies.

Drug: Semaglutide with 4 meal strategies

Interventions

Semaglutide with 4 meal strategies DRUG

The blinded drug will be used in addition to the participants routine closed-loop insulin pump therapy. It will be administered through subcutaneous injection on a weekly basis. The first 12 weeks will include progressively increasing doses of the drug whereby, the dose increases every 4 weeks. Once the maximum tolerated dose is achieved after 12 weeks, participants will undergo 4 meal strategies in a randomized order. These include (in no particular order); full carbohydrate counting with rapid-acting insulin, SMA with rapid-acting insulin, SMA with Lyumjev and fully closed-loop system with Lyumjev. Each meal strategy will be 3 weeks in duration and will occur sequentially in the designated order.

Weekly semaglutide (Ozempic®) injections on regular closed-loop insulin pump therapy

Placebo with 4 meal strategies DRUG

The blinded drug will be used in addition to the participants routine closed-loop insulin pump therapy. It will be administered through subcutaneous injection on a weekly basis. The first 12 weeks will include progressively increasing doses of the drug whereby, the dose increases every 4 weeks. Once the maximum tolerated dose is achieved after 12 weeks, participants will undergo 4 meal strategies in a randomized order. These include (in no particular order); full carbohydrate counting with rapid-acting insulin, SMA with rapid-acting insulin, SMA with Lyumjev and fully closed-loop system with Lyumjev. Each meal strategy will be 3 weeks in duration and will occur sequentially in the designated order.

Weekly placebo injections on regular closed-loop insulin pump therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• 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)
• 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.

You may not qualify if:

• Use of GLP1-RAs within the last 4 weeks.
• Use of any anti-hyperglycemic agent other than insulin within the last 2 weeks.
• Planned or ongoing pregnancy
• Breastfeeding
• 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
• Severe diabetic ketoacidosis (DKA) within the last 6 months ("severe" referring to need to present to medical attention and requirement of intravenous insulin)
• Prior history of acute pancreatitis, chronic pancreatitis, or gallbladder disease
• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
• Severe impairment of renal function with eGFR \<30 mL/min/1.73 m2 (using CKD-EPI formula), measured within the last 12 months
• Clinically significant diabetic retinopathy or gastroparesis, as per the clinical judgment of the investigator
• Bariatric surgery within the last 6 months.
• 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).
• Body mass index ≤ 21 kg/m2
• 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)
• Concern for safety of the participant, as per the clinical judgment of the primary investigator

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

Research Institute of the McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Insulin Resistance

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Central Study Contacts

Gabrielle Kemp, Registered Nurse

CONTACT

(438) 886-2171; gabrielle.kemp@rimuhc.ca

Nicholas Sabelli, B.Sc. (Hons)

CONTACT

(514) 377-9455; nicholas.sabelli@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Endocrinology & Metaolism

Model Details: randomized placebo-controlled crossover 2x3 factorial designed trial

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: April 26, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

CA (1)