Clinical trial NCT05402579: Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk
Official title: Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk (DaNGER)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes Type 2
DKA
Diabetic Ketoacidosis
Keywords: DKA
SGLT2i
Diabetes Type 2
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
name: University Health Network, Toronto
name: Sault Area Hospital
First posted: 2022-06-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cases: Patients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA will be eligible for inclusion in our study.

Controls: There are two sources for controls. \[1\] Patients hospitalized at one of the participating hospitals who were on an SGLT2i and do not have DKA. \[2\] Population controls using publicly available data from the Canadian Longitudinal Study on Aging (CLSA) database.

Brief summary: Sodium glucose co-transporter 2 (SGLT2) inhibitors have revolutionized care for people living with type 2 diabetes mellitus (T2DM). They reduce a person's risk of heart failure, renal failure, myocardial infarction, stroke, cardiovascular mortality, and potentially all-cause mortality. Remarkably, some of these benefits also extend to people who do not have T2DM. While the benefits of SGLT2 inhibitors are impressive, there is one life-threatening side effect associated with their use: diabetic ketoacidosis (DKA). The ability to predict which patients are at highest risk of DKA is needed to sufficiently mitigate this risk. Moreover, considering the impressive benefits of SGLT2 inhibitors, identifying patients at the lowest risk of SGLT2 inhibitor-associated DKA is also important so that providers do not overestimate risk in those who stand to benefit most.

Advances in genomic technologies and related analyses have provided unprecedented opportunities to bring genomics-driven precision medicine initiatives to the forefront of clinical research. Leading these developments has been the progress made by genome-wide association studies (GWAS) due to decreasing genotyping costs, and consequently, the ability to routinely study large numbers of patients. These approaches allow for systematic screening of the genome in an unbiased manner and have accelerated the discovery of genetic variants and novel biological processes that contribute to the development of adverse treatment outcomes.

By using innovative approaches, which harness large cohorts of population controls, sample size limitations that are associated with rare adverse drug reactions such as SGLT2 inhibitor-associated DKA can be overcome. The DANGER study represents a highly innovative new direction wherein partnership among basic science researchers and computational biologists will lead to the application of genomic techniques to identify genetic variants that may be associated with SGLT2 inhibitor-associated DKA.


Eligibility criteria: Inclusion Criteria:

To be considered eligible for participation in this study, a participant must meet each of the following criteria:

1. Be 18 years or older and have a diagnosis of type 2 diabetes mellitus.
2. Have been admitted to hospital with SGLT2 inhibitor-associated DKA (cases) or admitted to hospital on an SGLT2 inhibitor and not have DKA (controls).
3. Be able to provide written consent (or, if patient is unable, have a substitute decision maker \[SDM\] available).

Exclusion Criteria:

A participant will be ineligible for participation in this study if he or she satisfies any one or more of the following criteria:

1. Diagnosis of type 1 diabetes mellitus.
2. Unable to spit 10mL into a vial.
3. A first degree relative has already been recruited into the study.
4. Had an alcohol binge before admission
5. Had prolonged fasting (\>48 hours) prior to hospital admission
6. Recently stopped their insulin (within the past 7 days prior to hospital admission)

Our study will not include children or pregnant women because SGLT2 inhibitors are not approved for use in either patient population.

Primary outcomes:
measure: Identification of genomic variants associated with an increased risk of SGLT2 inhibitor-associated DKA
timeFrame: One year
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Joseph's Health Centre (Unity Health Toronto)
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital (University Health Network)
state: Ontario
Study officials:
References: