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

July 7, 2023 updated by: Mount Sinai Hospital, Canada

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

200

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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
      • Toronto, Ontario, Canada

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 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

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.

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

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

  • Observational Models: Case-Control
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cases
Patients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA
Genetic: Genomic analysis
Genetic samples will be collected using a DNA saliva collection kit (Oragene: OG-510) and will be sent for genome-wide genotyping to The Centre for Applied Genomics in The Hospital for Sick Children (SickKids)
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.
Genetic: Genomic analysis
Genetic samples will be collected using a DNA saliva collection kit (Oragene: OG-510) and will be sent for genome-wide genotyping to The Centre for Applied Genomics in The Hospital for Sick Children (SickKids)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of genomic variants associated with an increased risk of SGLT2 inhibitor-associated DKA
Time Frame: One year
Genetic ancestry will be calculated using principal component analyses and outliers will be removed. GWAS will be performed with SAIGE, including genetic ancestry and the relevant clinical/demographic variables as covariates, to identify genetic variants associated with SGLT2 inhibitor-associated DKA.
One year

Collaborators and Investigators

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

Sponsor

Mount Sinai Hospital, Canada

Collaborators

University Health Network, Toronto
Unity Health Toronto
Sault Area Hospital

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)

July 29, 2022

Primary Completion (Estimated)

June 6, 2024

Study Completion (Estimated)

June 6, 2024

Study Registration Dates

First Submitted

May 30, 2022

First Submitted That Met QC Criteria

May 30, 2022

First Posted (Actual)

June 2, 2022

Study Record Updates

Last Update Posted (Actual)

July 11, 2023

Last Update Submitted That Met QC Criteria

July 7, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTO 3737

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

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.

Clinical Trials on Diabetic Ketoacidosis

Clinical Trials on Genomic analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hong Kong

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe