Clinical trial NCT05368220: Translating Genetic Knowledge Into Clinical Care in Non-Autoimmune Diabetes
Official title: TRANSLATE - Translating Genetic Knowledge Into Clinical Care in Non-Autoimmune Diabetes
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Diabetes Mellitus, Type 2
Diabetes, Gestational
Keywords: Precision medicine
Personalized medicine
Genetics
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Steno Diabetes Center Copenhagen
name: BGI Europe
name: Intomics A/S
name: Rigshospitalet, Denmark
name: Danish National Genome Center
name: Nordsjaellands Hospital
name: Herlev Hospital
name: Hvidovre University Hospital
First posted: 2022-05-10
Enrollment: 6500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients in the target groups with non-autoimmune/non-T1D attending SDCC or pregnant women with gestational diabetes attending one of the obstetric clinics in the project will be offered a genetic test.

Brief summary: The aim of TRANSLATE is to implement genetic information directly into patient care to improve diagnosis and treatment of non-autoimmune diabetes. This project is the first large-scale implementation of systematic genetic testing within a common, non-communicable, chronic disease in Denmark, and will spearhead efforts to advance personalized medicine in Denmark.

The project will contribute to establishing technology, workflow, and evidence on how to implement and communicate actionable genetic information to clinicians and patients in a generalized format. These developments are pivotal for personalized medicine to reach broader clinical application.

Detailed description: The TRANSLATE project is an integrative project with multifaceted goals, that can be broken down into two main columns. The foundation for both columns is the WGS analysis in a clinical diagnostic setting in order to guide patient treatment. Patients are not randomized and the inclusion and exclusion criteria are deliberately broad and minimal, respectively.

The first column is the clinical development project, which seeks to complete a novel diagnostic process. This column will develop new pipelines and uncover barriers and challenges associated with gene-based precision medicine to facilitate sustainable implementation of gene-based precision medicine beyond the TRANSLATE project.

During the project, we wish to focus on potential barriers against a broad application of gene-based precision medicine in a common disease. These may include:

* Challenges pertaining to the selection of variants that are deemed clinically actionable, automation of genetic interpretation/translation, and the feasibility of large-scale precision medicine implementation
* Ethical concerns of patients, clinicians, and other technicians with regard to the application and utility of genetic information
* Validity and limitations of current computational pipelines for variant calling including the calling of structural variants and aggregate genetic tools
* Challenges regarding the interoperability of IT systems and databases nationally in Denmark, specifically how central databases can be linked to clinical end-users
* How implementation of genetic analyses affects clinical decision-making and/or clinical trajectories, both qualitatively and quantitatively

The second column is a register-based research project in which we will utilize data from the patients to advance gene-based precision medicine. In this column we will both address how to establish comprehensive research infrastructure, as well as answer specific research questions. We will address how to combine and harmonize genetic data with other Danish registry sources. We will use the newly established methodologies to focus on the following research areas with respect to patient stratification, clinical trajectories, complication development, and other clinically relevant outcomes:

* Polygenic risk scores
* Machine learning algorithms
* Combined polygenic and monogenic traits
* Non-coding variation
* Structural variation, specifically exon deletions and duplications, which have previously been shown as a cause of monogenic diabetes

Eligibility criteria: Inclusion Criteria:

* Any case of non-T1D defined as debut \>30 years of age, OR debut \<30 years of age AND negative autoantibodies
* Any case of diabetes diagnosed in pregnancy (obstetric departments)

Exclusion Criteria:

* Age \<18 years
* Inability to provide informed consent

Primary outcomes:
measure: Selection of clinically actionable genetic variation in diabetes
timeFrame: Until final patient inclusion (May 2025) + 2 years (May 2027)
measure: Ethical concerns regarding the application and utility of genetic information
timeFrame: Until final patient inclusion (May 2025) + 2 years (May 2027)
measure: Validity and limitations of current computational pipelines
timeFrame: Until final patient inclusion (May 2025) + 2 years (May 2027)
measure: Interoperability of IT systems and databases
timeFrame: Until final patient inclusion (May 2025) + 2 years (May 2027)
measure: Impact on clinical decision-making and clinical trajectories
timeFrame: Until final patient inclusion (May 2025) + 2 years (May 2027)
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Hillerød
country: Denmark
facility: Hillerød Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
Study officials:
affiliation: University of Copenhagen
name: Torben Hansen, PhD
role: PRINCIPAL_INVESTIGATOR
References: