Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk (DaNGER)

Status: Recruiting
Location: See all (2) locations...
Intervention Type: Genetic
Study Type: Observational
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
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 100
Healthy Volunteers: f
View:

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

• Be 18 years or older and have a diagnosis of type 2 diabetes mellitus.

• Have been admitted to hospital with SGLT2 inhibitor-associated DKA (cases) or admitted to hospital on an SGLT2 inhibitor and not have DKA (controls).

• Be able to provide written consent (or, if patient is unable, have a substitute decision maker \[SDM\] available).

Locations
Other Locations
Canada
St. Joseph's Health Centre (Unity Health Toronto)
RECRUITING
Toronto
Toronto General Hospital (University Health Network)
RECRUITING
Toronto
Contact Information
Primary
Michael Fralick, MD, PhD
mike.fralick@sinaihealth.ca
4165864800
Time Frame
Start Date: 2022-07-29
Estimated Completion Date: 2025-02-01
Participants
Target number of participants: 60
Treatments
Cases
Patients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA (60 cases).
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 (1000 controls via CLSA).
Sponsors
Collaborators: Sault Area Hospital, Unity Health Toronto, University Health Network, Toronto
Leads: Mount Sinai Hospital, Canada

This content was sourced from clinicaltrials.gov

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