Low Dose Empagliflozin in Adults With Type 1 Diabetes on Closed Loop Insulin System

NCT04450563 | Completed Phase 1

• 1 other identifier: 2021 - 6542
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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. Empagliflozin is used in type 2 diabetes; it allows for glucose to be removed through the urine. 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. The purpose of our study is to see if a small dose of empagliflozin (2.5 mg and 5 mg) is enough to help those who cannot achieve adequate glucose control on a closed-loop insulin system. The primary hypotheses of the study are the following:

1. 1.The use of empagliflozin 2.5 mg daily will increase time in range compared to placebo for those on the closed-loop system.
2. 2.The use of empagliflozin 5 mg daily will increase time in range compared to placebo for those on the closed-loop system.

Conditions

Type 1 Diabetes

Keywords

Diabetes mellitus, type 1; Artificial pancreas; Closed-loop system; Insulin; Empagliflozin; SGLT2 inhibitor

Outcome Measures

Primary Outcomes (2)

• Percentage of time of plasma glucose levels spent in target range (placebo vs empagliflozin 2.5 mg)

  Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs. empagliflozin 2.5 mg ono closed-loop insulin system.

  10 days

• Percentage of time of plasma glucose levels spent in target range (placebo vs empagliflozin 5 mg)

  Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs. empagliflozin 5 mg ono closed-loop insulin system.

  10 days

Secondary Outcomes (11)

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

  10 days (for each intervention)

• Percentage of time spent in the following ranges of glucose levels: below 3.9, 3.3 and 2.8 mmol/L

  10 days

• Percentage of time spent in the following ranges of glucose levels: above 7.8, 10, 13.9, and 16.7 mmol/L

  10 days

• Average glucose level

  10 days

• Percentage coefficient of variation of glucose levels

  10 days

Study Arms (3)

Placebo + closed-loop insulin system

ACTIVE COMPARATOR

Drug: 14-day outpatient intervention

Empagliflozin 2.5 mg + closed-loop insulin system

EXPERIMENTAL

Drug: 14-day outpatient intervention

Empagliflozin 5 mg + closed-loop insulin system

EXPERIMENTAL

Drug: 14-day outpatient intervention

Interventions

14-day outpatient intervention DRUG

The patient will be on the closed-loop insulin system and the intervention drug (placebo, empagliflozin 2.5 mg, or empagliflozin 5 mg) for 14 days. Insulin reductions will be made to avoid hypoglycemia with the drug agent. Remote contact around Day 4 (+/- 2 days) will be made to optimize insulin settings. The last 10 days will be used to assess continuous glucose monitoring data during each intervention. A wash-out period of 7 - 21 days will separate each intervention.

Empagliflozin 2.5 mg + closed-loop insulin system; Empagliflozin 5 mg + closed-loop insulin system; Placebo + closed-loop insulin system

Eligibility Criteria

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

You may qualify if:

• A clinical diagnosis of type 1 diabetes 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)
• Insulin pump use (of any modality) for minimum 3 months
• Agreement to the use of highly effective method of birth control in women of child-bearing age 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.
• Time in range (3.9 - 10.0 mmol/L) \< 70% as per CGM readings of the last 10 days during a 2-week run-in period on the closed-loop insulin delivery system.

You may not qualify if:

• Current or \< 2 week use of any other anti-hyperglycemic agent other than insulin
• Current or \</= 1 month use of supra-physiological doses of oral glucocorticoids
• Requirement for regular use of acetaminophen (which may decrease CGM fidelity)
• Planned or ongoing pregnancy
• Breastfeeding individuals
• 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 within the last 3 years ("severe" referring to need to present to medical attention and requirement of intravenous insulin)
• Active infection of any kind at the time of study enrolment, or any active foot ulcer
• Recurrent infections (i.e. more than 2 in 1 year) of the following: genital, urinary tract infections, soft tissue, joint, or bone
• Known severe peripheral vascular disease including the following: symptomatic claudication, loss of peripheral pulses, signs of peripheral arterial insufficiency as per initial clinical exam, previously documented insufficiency as per ankle or toe brachial index, prior amputations due to peripheral vascular disease
• Osteoporosis defined as prior fragility fracture, previously measured bone mineral density with T or Z score \< -2.5, or need for anti-osteoporotic medications
• Glomerular filtration rate less than 30 mL/minutes/1.73 m2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.
• 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)
• Prior adverse reaction to SGLT2 inhibitors (e.g. empagliflozin, dapagliflozin)
• Inability to travel to the research center within 3 hours if needed during the study interventions

Sponsors & Collaborators

• McGill University: lead

Study Sites (1)

Clinique Médicale Hygea

Montreal, Quebec, H4A 3T2, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

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

Study Officials

• Ahmad Haidar, PhD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  STUDY CHAIR

• Michael Tsoukas, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Melissa-Rosina Pasqua, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 29, 2020
• Study Start: November 2, 2020
• Primary Completion: January 5, 2022
• Study Completion: January 13, 2022
• Last Updated: October 12, 2022

Record last verified: 2022-10

Locations

CA (1)