Continuous Ketone Monitoring in People With Type 1 Diabetes Using SGLT2 Inhibitors

NCT06753994 | Recruiting Phase 1

• 1 other identifier: 2024-0807
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes is an autoimmune disease where the body attacks the insulin-producing cells in the pancreas. In the absence of insulin, the body is unable to effectively use glucose for energy, resulting in high blood sugar levels. This leads to a lifelong need for intensive insulin therapy to manage blood sugar and prevent complications arising from elevated blood glucose levels. When insulin is low, the body produces ketone bodies. If ketone levels rise too high, they can lead to the dangerous condition known as diabetic ketoacidosis. Diabetic ketoacidosis remains a leading cause of mortality in children and young adults with type 1 diabetes. Sodium/glucose cotransporter 2 inhibitors, such as empagliflozin, are effective in lowering blood sugar but can also increase ketone levels, raising the risk of diabetic ketoacidosis. Empagliflozin is approved for type 2 diabetes and has demonstrated benefits in type 1 diabetes, including improved blood sugar control at lower doses and reduced risks of chronic kidney disease and mortality at higher doses. However, its use in type 1 diabetes is still off-label due to the heightened risk of diabetic ketoacidosis. Using empagliflozin at a commercial dose safely is desirable to maximize its potential renal benefits in type 1 diabetes. While there are measures to monitor ketone levels, current methods, such as finger prick tests, often detect issues too late to prevent diabetic ketoacidosis. Continuous ketone monitoring offers real-time tracking of ketone levels, which could enable timely interventions to maintain safe levels. Moreover, there is currently no data on continuous ketone metrics in individuals with type 1 diabetes using sodium/glucose cotransporter 2 inhibitors. We aim to understand the dynamics of ketone levels in people with type 1 diabetes using empagliflozin, including in challenging situations such as during exercise and low-carbohydrate diets while on sodium/glucose cotransporter 2 inhibitors. To this end, we will conduct an open- label, single-arm, outpatient study where 24 participants with type 1 diabetes will use continuous ketone monitoring for a 4-week run-in, followed by empagliflozin 2.5 mg for four weeks and then empagliflozin 10 mg for nine weeks. Participants will perform an exercise sub-study during the fourth week of the continuous ketone monitoring run-in and during the eighth week of empagliflozin 10 mg use. Certain participants will be invited to undergo a low-carbohydrate diet during the last week of empagliflozin 10 mg use. The results, if positive, may lead to i) novel long-term (6 months) data on ketone levels in those with type 1 diabetes using empagliflozin, including individuals on multiple daily injections and closed-loop therapy across a wide range of body mass index, ii) data on the relationship between empagliflozin, exercise, low-carbohydrate diets, and type 1 diabetes, and iii) the creation of important metrics for ketone thresholds that have not yet been characterized. Furthermore, we hope this preliminary study will inform future research to investigate the use of continuous ketone monitoring to allow for the safe use of higher doses of sodium/glucose cotransporter 2 inhibitors in people with type 1 diabetes.

Conditions

Diabetes; Type1diabetes; T1D

Keywords

CKM; Continous Ketone Monitoring; Empagliflozin; SGLT2i; SGLT2 inhibitors; Sodium-glucose cotransporter-2 inhibitors; Low-carb; Exercise

Outcome Measures

Primary Outcomes (1)

• Number of events ≥ 0.6 mmol/L, ≥ 0.8 mmol/L ≥ 1.5 mmol/L, ≥ 3.0 mmol/L that last for more than one hour

  Number of events at each range that last for more than one hour. This will be compared between i) each study period (run-in, 2.5 mg, 10 mg etc) and ii) the first week and the remaining weeks for each study period

  17 weeks

Other Outcomes (2)

• Beta-hydroxybutyrate level (mmol/L)

  17 weeks

• Time spent above various thresholds of beta-hydroxybutyrate concentrations:

  17 weeks

Study Arms (1)

SGLT2 inhibitor dose scalation to maximum tolerated dose with Continuous Ketone Monitor

EXPERIMENTAL

This is a single arm study where 24 participants with T1D will use a CKM for a 4-week run-in followed by empagliflozin 2.5 mg for four weeks then empagliflozin 10 mg for nine weeks. Participants will perform an exercise sub-study during the fourth week of the CKM run-in and during the eighth week of empagliflozin 10 mg use. Certain participants will be invited to undergo a low-carb diet during the last week of empagliflozin 10 mg use.

Drug: SGLT-2 inhibitor

Interventions

SGLT-2 inhibitor DRUG

Empagliflozin is an SGLT2i that aids in blood glucose reduction through the urination of excess glucose in the context of hyperglycemia. In this study, participants will start with a dose of 2.5 mg of empagliflozin for four weeks, which will then be increased to 10 mg for the following nine weeks.

Also known as: Empagliflozin, Sodium-glucose cotransporter-2 (SGLT2) inhibitors

SGLT2 inhibitor dose scalation to maximum tolerated dose with Continuous Ketone Monitor

Eligibility Criteria

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

You may not qualify if:

• DKA or severe hypoglycemia within the last six months.
• Current or recent use of any anti-hyperglycemic agent other than insulin (≤ one month for GLP1-RA, ≤ one week for all others).
• Current or ≤ one-month use of supraphysiological doses of glucocorticoids.
• Body mass index \< 20 kg/m2.
• Glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 as per CKD-EPI formula with creatinine levels measured within the last two months.

Sponsors & Collaborators

• McGill University: lead

Study Sites (1)

Hygea Medical Clinic

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus; Motor Activity

Interventions

Sodium-Glucose Transporter 2 Inhibitors; empagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Michael Tsoukas, M.D.

  Clinique Medicale Hygea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Linden Perz, Bachelor of Medical Sciences

CONTACT

5144045621; linden.perz@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Endocrinologist

Model Details: This is an open- label, single-arm, outpatient study where 24 participants with type 1 diabetes will use continuous ketone monitoring for a 4-week run-in, followed by empagliflozin 2.5 mg for four weeks and then empagliflozin 10 mg for nine weeks. Participants will perform an exercise sub-study during the fourth week of the continuous ketone monitoring run-in and during the eighth week of empagliflozin 10 mg use. Certain participants will be invited to undergo a low-carbohydrate diet during the last week of empagliflozin 10 mg use.

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: December 31, 2024
• Study Start: December 5, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

CA (1)