NCT06535542

Integrating Whole Genome Sequencing and Digital Twins Into the Management of Hypercholesterolemia in Emiratis

A Randomized Trial of Integrating Whole Genome Sequencing and Digital Twins Into the Management of Hypercholesterolemia in Emiratis

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Abu Dhabi Health Services Company · Other Government
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

This pilot study investigates integrating whole genome sequencing and digital twin technology for managing hypercholesterolemia in Abu Dhabi clinics. It aims to establish protocols for larger future studies and incorporate genomic insights into routine medical care.

Detailed description

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the Middle East, with hypercholesterolemia being a significant contributor. Genetic mechanisms of hypercholesterolemia in this region are not well understood. Autosomal dominant hypercholesterolemia is a major factor, yet only \~7% of Emiratis with familial hypercholesterolemia (FH) have these mutations. In 2013, Talmud et al. identified common variants through genome-wide association studies (GWAS) that suggest a polygenic cause for hypercholesterolemia in mutation-negative FH patients. A polygenic risk score based on 12 SNPs was validated in White European populations and is used in the UK's NHS diagnostic pipeline. Distinguishing polygenic hypercholesterolemia from FH without genetic testing is challenging. These patients exhibit familial moderate hypercholesterolemia and early coronary heart disease, with elevated LDL-C, normal triglycerides, and no tendon xanthoma. Their cardiovascular risk is similar to monogenic FH with age. Statins, though commonly prescribed for ASCVD prevention, can cause musculoskeletal symptoms leading to poor adherence, discontinuation, elevated cholesterol, and increased cardiovascular risk. Many patients fail to achieve target LDL-C levels due to suboptimal dosing. Certain gene variants increase the risk of statin side effects. This study seeks to integrate whole genome sequencing (WGS) technology in a clinical setting through an innovative digital twin platform. This platform allows clinicians to assess monogenic and polygenic risks in real-time and make informed statin prescribing and management decisions.

Conditions

• Hypercholesterolemia, Autosomal Dominant
• Hypercholesterolemia, Autosomal Recessive
• Familial Combined Hypercholesterolemia

Interventions

Type	Name	Description
GENETIC	Whole Genome Sequencing	Participants in this arm will have their blood sample analyzed by whole-genome sequencing (WGS) and will be given access to Predictiv™ Deoxyribonucleic acid (DNA)-based digital twin platform, a web-based interactive application with WGS results. The platform will include positive monogenic and polygenic Familial Hypercholesterolemia results and pharmacogenomics results on statins and clopidogrel. A report of positive monogenic variants will be included in their medical record. This may also include genes on the American College of Medical Genetics and Genomics (ACMG) secondary findings (SF) version 3.2 list if the participant consents to receive these incidental findings. The report will only include pathogenic, likely pathogenic, and variant of uncertain significance (VUS) results.

Timeline

• Start date: 2024-07-29
• Primary completion: 2025-12-15
• Completion: 2026-07-15
• First posted: 2024-08-02
• Last updated: 2025-03-25

Locations

1 site across 1 country: United Arab Emirates