Translating Genetic Knowledge Into Clinical Care in Non-Autoimmune Diabetes

NCT05368220 | Enrolling By Invitation

• 1 other identifier: 9090-00078B
• Study Type: observational
• Target: 6,500
• Locations: 1 country
• Sites: 5

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.

Conditions

Diabetes Mellitus, Type 2; Diabetes, Gestational

Keywords

Precision medicine; Personalized medicine; Genetics

Outcome Measures

Primary Outcomes (5)

• Selection of clinically actionable genetic variation in diabetes

  Using mixed methods such as gene burden investigations, workgroups, interviews, etc. challenges related to the selection of clinically actionable genetic variants and automation of interpretation/translation will be delineated.

  Until final patient inclusion (May 2025) + 2 years (May 2027)

• Ethical concerns regarding the application and utility of genetic information

  The project will address how patients, clinicians, technicians etc. shape their understanding of the utility and challenges associated with gene-based precision medicine using ethnographic methods such as field observations and semi-structured interviews.

  Until final patient inclusion (May 2025) + 2 years (May 2027)

• Validity and limitations of current computational pipelines

  By comparing computational and analytical methods, the project will investigate the validity and limitations of different computational pipelines. This includes handling of single nucleotide variants, as well as structural variation.

  Until final patient inclusion (May 2025) + 2 years (May 2027)

• Interoperability of IT systems and databases

  The project will address the flow of data to and from clinical end-users, through centralized databases, both with respect to how the data flow is perceived by users and potential challenges, and how interoperability can be improved to enhance clinical utility. The project will also address how to harmonize data from different sources.

  Until final patient inclusion (May 2025) + 2 years (May 2027)

• Impact on clinical decision-making and clinical trajectories

  Using mixed methods such as mapping of clinical trajectories through clinical registries and qualitative methods such as interviews, workgroups, etc., the project will investigate how implementation of gene-based precision diabetes impacts clinical decision making.

  Until final patient inclusion (May 2025) + 2 years (May 2027)

Study Arms (2)

Patients with non-autoimmune diabetes (type 2 diabetes)

Any case of non-T1D defined as: * Debut \>30 years of age OR * Debut \<30 years of age AND negative autoantibodies treated at Steno Diabetes Center Copenhagen

Other: Whole genome sequencing

Patients with gestational diabetes

Any case of diabetes diagnosed in pregnancy treated at the following obstetric clinics in the Capital Region in Denmark: Rigshospitalet, Nordsjællands Hospital, Herlev Hospital, Hvidovre Hospital

Other: Whole genome sequencing

Interventions

Whole genome sequencing OTHER

Each participant will have WGS performed in order to report on clinically actionable genetic variation in diabetes.

Also known as: WGS

Patients with gestational diabetes; Patients with non-autoimmune diabetes (type 2 diabetes)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University of Copenhagen: lead
• Steno Diabetes Center Copenhagen: collaborator
• BGI Europe: collaborator
• Intomics A/S: collaborator
• Rigshospitalet, Denmark: collaborator
• Danish National Genome Center: collaborator
• Nordsjaellands Hospital: collaborator
• Herlev Hospital: collaborator
• Hvidovre University Hospital: collaborator

Study Sites (5)

Rigshospitalet

Copenhagen, Denmark

Location

Herlev Hospital

Herlev, Denmark

Location

Steno Diabetes Center Copenhagen

Herlev, Denmark

Location

Hillerød Hospital

Hillerød, Denmark

Location

Hvidovre Hospital

Hvidovre, Denmark

Location

Related Links

• Study website

Biospecimen

Retention: SAMPLES WITH DNA

Two 10ml EDTA blood tubes are collected, from which buffy coat is isolated and DNA is extracted for whole genome sequencing and quality control. Samples are stored for up to two years in order to repeat the analysis before being destroyed.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes, Gestational

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Torben Hansen, PhD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 10, 2022
• Study Start: May 6, 2022
• Primary Completion: May 31, 2025
• Study Completion (Estimated): May 31, 2027
• Last Updated: May 17, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (5)