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

Sponsor
Washington University School of Medicine (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05541484
Collaborator
Juvenile Diabetes Research Foundation (Other)
20
Enrollment
1
Location
2
Arms
23
Anticipated Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Dapagliflozin 10 MG [Farxiga]
  • Device: Biosense Breath Ketone Analyzer
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Participants will test the breath ketone analyzer under usual care conditions followed by usual care plus SGLT2i treatment (GROUP A) or with usual care plus SGLT2i treatment followed by usual care (GROUP B). At the end of each segment, participants will undergo a one-day insulin withdrawal period with more intense monitoring.Participants will test the breath ketone analyzer under usual care conditions followed by usual care plus SGLT2i treatment (GROUP A) or with usual care plus SGLT2i treatment followed by usual care (GROUP B). At the end of each segment, participants will undergo a one-day insulin withdrawal period with more intense monitoring.
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Ketone Monitoring in T1D: Effect of SGLT2i During Usual Care and With Insulin Deficiency
Anticipated Study Start Date :
Sep 30, 2022
Anticipated Primary Completion Date :
Aug 31, 2024
Anticipated Study Completion Date :
Aug 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Other: Group A

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: Dapagliflozin 10 MG [Farxiga]
See above.

Device: Biosense Breath Ketone Analyzer
The hand-held device tests ketones in exhaled breath
Other: Group B

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: Dapagliflozin 10 MG [Farxiga]
See above.

Device: Biosense Breath Ketone Analyzer
The hand-held device tests ketones in exhaled breath

Outcome Measures

Primary Outcome Measures

  1. Ketone levels measured in blood and breath in persons with T1D in persons with T1D [4 weeks]

    Correlation of capillary beta hydroxybutyrate measurements with breath ketone measurements.

Secondary Outcome Measures

  1. Ketone levels in persons with T1D during usual care versus usual care plus SGLT2i treatment [2 weeks each treatment period]

    Comparison of ketone levels (BOHB and BrAce) during usual care and usual care plus treatment with an SGLT2i.

Other Outcome Measures

  1. Ketone levels in persons with T1D undergoing insulin withdrawal [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  • Use of personal CGM, only Dexcom G6 will be permitted for data consistency

  • Use of cellular phone (iOS7 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

  • 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Washington University Saint Louis Missouri United States 63110

Sponsors and Collaborators

  • Washington University School of Medicine
  • Juvenile Diabetes Research Foundation

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Janet McGill, Professor of Medicine, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT05541484
Other Study ID Numbers:
  • 202206078
First Posted:
Sep 15, 2022
Last Update Posted:
Sep 15, 2022
Last Verified:
Sep 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Janet McGill, Professor of Medicine, Washington University School of Medicine
ketosis
beta hydroxybutyrate
sodium glucose co-transport inhibitor
breath ketone
Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Dapagliflozin

Study Results

No Results Posted as of Sep 15, 2022