A Randomized Trial of Integrating Whole Genome Sequencing and Digital Twins Into the Management of Hypercholesterolemia in Emiratis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Diagnostic capabilities
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Investigative site personnel will obtain the subject's identification number and study treatment assignment from the randomizer. Participants and all personnel directly involved in the study conduct will be blinded to the arm assignment until 2-3 months after enrollment when the whole-genome sequencing (WGS) report is generated.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with 2 or more LDL-C levels greater than 190 mg/dL or 5.0 mmol/L in the past 12 months
- •Undiagnosed patients meeting Possible, Probable or Definitive FH criteria according to Dutch Lipid Clinic Network (DLCN) criteria (Eur Heart J. 2011 Jul;32(14):1769-
- •doi: 10.1093/eurheartj/ehr
- •Epub 2011 Jun 28.)
- •Patients who have not been on anti-lipidemic medication in the past 3 months
- •Ages 18-55
- •Emirati national
- •All patients must be fluent in English or Arabic
排除标准
- •- Patients who do not meet the above criteria
- •Patients with a previous diagnosis of FH
- •Patients with a progressive debilitating illness
- •Patient with untreated hypothyroidism, history of proteinuria, obstructive liver disease, chronic renal failure, human immunodeficiency virus infection, or on immunosuppressant or steroid or psychiatric medications
- •Patients with untreated clinical anxiety or depression (as measured by a Hospital Anxiety and Depression Scale (HADS) score of ≥ 16 on the depression subscale)
- •Patients who are pregnant
研究组 & 干预措施
Standard of Care Group
20 participants who are randomized to not have whole-genome sequencing performed on their sample. These participants will have standard-of-care familial hypercholesterolemia (FH) evaluation using medical history and family history only. They will not receive genetic results or Predictiv™ Digital Twin results as part of this study.
WGS + Digital Twin Group
20 participants who are randomized to have whole-genome sequencing performed on their sample and given access to Predictiv™ Digital Twin. These participants will meet with a genetic counselor for results disclosure and training to access the Predictiv™ Digital Twin platform.
干预措施: Whole Genome Sequencing (Genetic)
结局指标
主要结局
Diagnostic capabilities
时间窗: From consent date until first documented report, up to 6 months
Diagnostic yield of standard-of-care (based on medical and family history) versus whole genome sequencing (WGS) for identifying monogenic and polygenic familial hypercholesterolemia.
次要结局
- Participant characteristics(Baseline)
- Prognostic capabilities of standard-of-care(Baseline to End of Study, up to 12 months)
- Changes in Health Care Utilization(Baseline to End of Study, up to 12 months)
- Resources Implementation for WGS in a clinical setting(Baseline to End of Study, up to 12 months)
- Change in Perceived Utility(Baseline, post-disclosure of results (approximately 2-3 months after enrollment), 6 months post-enrollment)
- Clinician Attitudes About WGS(Baseline)