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

December 8, 2023 updated by: Washington University School of Medicine
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will consist of 4 distinct segments that include routine testing of ketones during usual care, during insulin deficiency, and while taking a SGLT2i in addition to usual care, then with insulin deficiency after the SGLT2i has reached steady state and ingested that morning. We will study 20 adults with T1D who are using Dexcom G6 continuous glucose monitor (CGM), plus any form of insulin delivery. Study participants will be randomized to Group A or Group B. Simultaneous ketone monitoring using a the Biosense® breath ketone analyzer (BKA) and capillary blood beta hydroxybutyrate (BOHB) measurement will be done 2-3 times daily for 2 weeks during each of the outpatient segments. This will generate >800 data points comparing breath acetone, measured in units called ACEs, versus capillary blood BOHB measurements for each 2 week period. On days of insulin withdrawal, which will take place on the Washington University Intensive Research Unit (IRU), frequent monitoring with capillary blood measurements of BOHB (Precision Xtra®, Abbott) will be compared with breath BrAce measurements (Biosense®, Readout) and laboratory measurements of BOHB and acetoacetate. Electrolytes and glucose will also be measured.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Contact:
        • Principal Investigator:
          • Janet B. McGill, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Pre-menopausal women not using acceptable birth control defined as abstinence, surgical sterilization, hysterectomy, hormonal contraception, IUD or proven effective barrier methods

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Group A: Usual care followed by usual care plus dapagliflozin
10 persons with T1D will check capillary beta hydroxybutyrate (BOHB) and concomitant breath acetone (BrAce) 2 - 3 times daily for 2 weeks during usual care, then undergo an insulin withdrawal visit. Subsequently, the Group A patients will repeat the paired measurements of BOHB and BrAce, 2 - 3 times daily for 2 weeks during usual care plus treatment with the SGLT2i dapagliflozin, 10 mg taken orally daily, followed by an insulin withdrawal visit.
Drug: SGLT2 inhibitor
See above.
Other Names:
  • Dapagliflozin 10mg (Farxiga)
Device: Biosense Breath Ketone Analyzer
The hand-held device tests ketones in exhaled breath
Other: Group B: Usual care plus dapagliflozin followed by usual care
10 persons with T1D will check capillary beta hydroxybutyrate (BOHB) and concomitant breath acetone (BrAce) 2 - 3 times daily for 2 weeks during usual care plus treatment with the SGLT2i dapagliflozin, 10 mg taken orally daily, then undergo an insulin withdrawal visit. Subsequently, the Group B patients will repeat the paired measurements of BOHB and BrAce, 2 - 3 times daily during usual care alone followed by an insulin withdrawal visit.
Drug: SGLT2 inhibitor
See above.
Other Names:
  • Dapagliflozin 10mg (Farxiga)
Device: Biosense Breath Ketone Analyzer
The hand-held device tests ketones in exhaled breath

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ketone levels measured in blood and breath in persons with T1D in persons with T1D
Time Frame: 4 weeks
Correlation of capillary beta hydroxybutyrate measurements with breath ketone measurements.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ketone levels in persons with T1D during usual care versus usual care plus SGLT2i treatment
Time Frame: 2 weeks each treatment period
Comparison of ketone levels (BOHB and BrAce) during usual care and usual care plus treatment with an SGLT2i.
2 weeks each treatment period

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ketone levels in persons with T1D undergoing insulin withdrawal
Time Frame: 2 days
Comparison of ketone levels (BOHB and BrAce) during insulin withdrawal after usual care and during insulin withdrawal after usual care plus treatment with an SGLT2i.
2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Juvenile Diabetes Research Foundation

Investigators

  • Principal Investigator: Janet B McGill, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 14, 2022

Primary Completion (Estimated)

December 1, 2023

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

September 12, 2022

First Submitted That Met QC Criteria

September 12, 2022

First Posted (Actual)

September 15, 2022

Study Record Updates

Last Update Posted (Estimated)

December 11, 2023

Last Update Submitted That Met QC Criteria

December 8, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202206078

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Data will be shared upon request and review of the Investigator

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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