Ketone Monitoring in T1D: Effect of SGLT2i During Usual Care and With Insulin Deficiency

NCT05541484 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 202206078
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This proposed study will test whether measurement of breath acetone (BrAce) can be used for the purpose of identifying ketosis (elevated ketones) in persons with type 1 diabetes (T1D). This is important for the potential use of sodium glucose co-transport inhibitors (SGLT2i) in persons with T1D.

Conditions

Diabetes Mellitus, Type 1

Keywords

ketosis; beta hydroxybutyrate; sodium glucose co-transport inhibitor; breath ketone

Outcome Measures

Primary Outcomes (2)

• Capillary Blood Beta-hydroxybutyrate (BOHB) During Outpatient Care

  Differences between usual care v dapagliflozin of capillary beta hydroxybutyrate (BOHB) measurements during outpatient care.

  Measurements were taken 2-3 times daily for 2 weeks

• Breath Acetone (BrACE) During Outpatient Care

  Differences of breath acetone (BrACE) measurements between usual care v dapagliflozin during outpatient care.

  Measurements were taken 2-3 times daily for 2 weeks

Other Outcomes (1)

• Ketone Levels in Persons With T1D Undergoing Insulin Withdrawal

  2 days

Study Arms (1)

Usual care (UC) or Dapagliflozin (DAPA)

OTHER

20 persons with T1D

Drug: SGLT2 inhibitor; Device: Biosense Breath Ketone Analyzer

Interventions

SGLT2 inhibitor DRUG

See above.

Also known as: Dapagliflozin 10mg (Farxiga)

Usual care (UC) or Dapagliflozin (DAPA)

Biosense Breath Ketone Analyzer DEVICE

The hand-held device tests ketones in exhaled breath

Usual care (UC) or Dapagliflozin (DAPA)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 1 diabetes for \>1 year
• Age 18 - 75, any gender, race or ethnicity
• HbA1c \<10%
• Stable insulin delivery method for the past 30 days
• Vision of 20/40 or better, including ability to read all device instructions and insulin pump settings
• Use of an insulin pump and ability to make adjustments to pump settings
• Insulin delivery by MDI with basal insulin (glargine U100) given in the morning OR willingness to transition to basal glargine given in the morning for at least 48 hours prior to insulin withdrawal visits
• Use of personal CGM, only Dexcom G6 will be permitted for data consistency
• Use of cellular phone (iOS11 and above or Android) with data capability with connectivity to Dexcom Clarity app and Biosense Ketone Monitoring app
• Willing to share CGM, capillary ketone results and BrACE data with the study group
• Able to understand the study requirements, risks and benefits and able to provide written informed consent
• Able to schedule the visits and perform study related tasks

You may not qualify if:

• History of DKA in the past 6 months, or more than 1 episode of DKA in the past 2 years
• Use of insulin degludec, insulin glargine U300 or insulin detemir as basal insulin and unwilling to transition to glargine given in the morning for at least 48 hours before the insulin withdrawal visits
• Use of an SGLT2i in the past 30 days or intolerance to SGLT2i use in the past for any reason
• Unstable heart disease, including hospitalization for any cardiac or vascular event in the past 6 months.
• eGFR \<30 ml/min/1.73m2 or hemoglobin \<11.0 g/dL measured in the past year
• Cancer that has been under treatment in the past 6 months, or treatment is likely in the 3 months after signing the consent, not including skin cancer or cancers under long-term hormonal reduction treatment (breast or prostate, no other active treatment)
• Psychiatric condition that interferes with daily activities or diabetes self-care, including substance abuse
• Any illness or condition that may interfere with study measurements, or contraindications for use of SGLT2i, based on investigator discretion (hemoglobinopathy, orthostatic hypotension)
• Unwilling to avoid alcohol during the active study periods, specifically to avoid alcohol for 4 hours prior to any breath ketone measurement
• Currently following or planning to adopt a diet that is low in carbohydrates (defined as \<90 grams of carbohydrate per day) or is expected to be ketogenic
• Use of oral or injected corticosteroids within the past 30 days or planned during the study period
• Taking disulfiram (due to interference with breath ketone measurements)
• History of vomiting episodes for any reason in the past 30 days, or hospitalization for cyclic vomiting in the past year
• History of urinary tract infection in the past 3 months
• Pregnancy, breast-feeding or intention of becoming pregnant during the study time period and up to 30 days after study completion

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (13)

• Dandona P, Mathieu C, Phillip M, Hansen L, Griffen SC, Tschope D, Thoren F, Xu J, Langkilde AM; DEPICT-1 Investigators. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2017 Nov;5(11):864-876. doi: 10.1016/S2213-8587(17)30308-X. Epub 2017 Sep 14.

  PMID: 28919061 BACKGROUND

• Mathieu C, Dandona P, Gillard P, Senior P, Hasslacher C, Araki E, Lind M, Bain SC, Jabbour S, Arya N, Hansen L, Thoren F, Langkilde AM; DEPICT-2 Investigators. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care. 2018 Sep;41(9):1938-1946. doi: 10.2337/dc18-0623. Epub 2018 Jul 19.

  PMID: 30026335 BACKGROUND

• Owen OE, Trapp VE, Skutches CL, Mozzoli MA, Hoeldtke RD, Boden G, Reichard GA Jr. Acetone metabolism during diabetic ketoacidosis. Diabetes. 1982 Mar;31(3):242-8. doi: 10.2337/diab.31.3.242.

  PMID: 6818074 BACKGROUND

• Garg SK, Peters AL, Buse JB, Danne T. Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol. Diabetes Technol Ther. 2018 Sep;20(9):571-575. doi: 10.1089/dia.2018.0246. Epub 2018 Aug 21. No abstract available.

  PMID: 30129772 BACKGROUND

• Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999 Nov-Dec;15(6):412-26. doi: 10.1002/(sici)1520-7560(199911/12)15:63.0.co;2-8.

  PMID: 10634967 BACKGROUND

• Hancock G, Sharma S, Galpin M, Lunn D, Megson C, Peverall R, Richmond G, Ritchie GAD, Owen KR. The correlation between breath acetone and blood betahydroxybutyrate in individuals with type 1 diabetes. J Breath Res. 2020 Oct 29;15(1):017101. doi: 10.1088/1752-7163/abbf37.

  PMID: 33027776 BACKGROUND

• Suntrup Iii DJ, Ratto TV, Ratto M, McCarter JP. Characterization of a high-resolution breath acetone meter for ketosis monitoring. PeerJ. 2020 Sep 24;8:e9969. doi: 10.7717/peerj.9969. eCollection 2020.

  PMID: 33024634 BACKGROUND

• Spanel P, Dryahina K, Rejskova A, Chippendale TW, Smith D. Breath acetone concentration; biological variability and the influence of diet. Physiol Meas. 2011 Aug;32(8):N23-31. doi: 10.1088/0967-3334/32/8/N01. Epub 2011 Jul 1.

  PMID: 21725144 BACKGROUND

• Rydosz A. A Negative Correlation Between Blood Glucose and Acetone Measured in Healthy and Type 1 Diabetes Mellitus Patient Breath. J Diabetes Sci Technol. 2015 Jul;9(4):881-4. doi: 10.1177/1932296815572366. Epub 2015 Feb 17.

  PMID: 25691653 BACKGROUND

• Herring RA, Shojaee-Moradie F, Garesse R, Stevenage M, Jackson N, Fielding BA, Mendis A, Johnsen S, Umpleby AM, Davies M, Russell-Jones DL. Metabolic Effects of an SGLT2 Inhibitor (Dapagliflozin) During a Period of Acute Insulin Withdrawal and Development of Ketoacidosis in People With Type 1 Diabetes. Diabetes Care. 2020 Sep;43(9):2128-2136. doi: 10.2337/dc19-2579. Epub 2020 Jul 8.

  PMID: 32641376 BACKGROUND

• Patel NS, Van Name MA, Cengiz E, Carria LR, Weinzimer SA, Tamborlane WV, Sherr JL. Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study. Diabetes Technol Ther. 2017 Nov;19(11):618-622. doi: 10.1089/dia.2017.0267. Epub 2017 Oct 25.

  PMID: 29068709 BACKGROUND

• Jones KE, Petersen MC, Markov AM, Salam M, Krutilova P, McKee AM, Bohnert KL, Adamson SE, McGill JB. Breath Acetone Correlates With Capillary beta-hydroxybutyrate in Type 1 Diabetes. J Diabetes Sci Technol. 2025 Apr 22:19322968251334640. doi: 10.1177/19322968251334640. Online ahead of print.

  PMID: 40260699 DERIVED

• Jones KE, Petersen MC, Markov AM, Salam M, Krutilova P, McKee AM, Bohnert KL, Adamson SE, McGill JB. Breath Acetone Correlates with Capillary beta-hydroxybutyrate in Type 1 Diabetes. medRxiv [Preprint]. 2025 Jan 31:2025.01.30.25321320. doi: 10.1101/2025.01.30.25321320.

  PMID: 39974120 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Ketosis

Interventions

Sodium-Glucose Transporter 2 Inhibitors; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Acidosis; Acid-Base Imbalance

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Janet McGill, Professor Medicine
• Organization: Washington University School of Medicine

jmcgill@wustl.edu

314-273-3929

Study Officials

• Janet B McGill, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will test the breath ketone analyzer under usual care or with usual care plus SGLT2i treatment. Each out patient segment will last two weeks. At the end of each out patient segment, participants will undergo a one-day insulin withdrawal period with more intense monitoring.

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 15, 2022
• Study Start: October 14, 2022
• Primary Completion: December 23, 2023
• Study Completion: December 23, 2023
• Last Updated: February 21, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-01

Locations

US (1)