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

NCT06535542 | Recruiting DMC

• 2 other identifiers: WGS_DT_2023DOH/CVDC/2023/926
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypercholesterolemia, Autosomal Dominant; Hypercholesterolemia, Autosomal Recessive; Familial Combined Hypercholesterolemia

Keywords

LDH; Familial Hypercholesterolemia; Whole Genome Sequencing; Digital Twins; Management of Hypercholesterolemia; Emirati; Randomized Controlled Trial; Sanger Sequencing; Predictiv Care; Genomic Medicine; Precision Medicine; Pharmacogenomics

Outcome Measures

Primary Outcomes (1)

• Diagnostic capabilities

  Diagnostic yield of standard-of-care (based on medical and family history) versus whole genome sequencing (WGS) for identifying monogenic and polygenic familial hypercholesterolemia.

  From consent date until first documented report, up to 6 months

Secondary Outcomes (6)

• Prognostic capabilities of standard-of-care

  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

• Participant characteristics

  Baseline

• Change in Perceived Utility

  Baseline, post-disclosure of results (approximately 2-3 months after enrollment), 6 months post-enrollment

• Changes in Health Care Utilization

  Baseline to End of Study, up to 12 months

Study Arms (2)

WGS + Digital Twin Group

EXPERIMENTAL

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.

Genetic: Whole Genome Sequencing

Standard of Care Group

NO INTERVENTION

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.

Interventions

Whole Genome Sequencing GENETIC

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.

WGS + Digital Twin Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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):1769-818. doi: 10.1093/eurheartj/ehr158. 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Abu Dhabi Health Services Company: lead
• Predictiv Care, Inc.: collaborator

Study Sites (1)

Abu Dhabi Health Research Center

Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates

RECRUITING

Related Publications (6)

• Hsieh HF, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res. 2005 Nov;15(9):1277-88. doi: 10.1177/1049732305276687.

  PMID: 16204405 BACKGROUND

• Wang J, Dron JS, Ban MR, Robinson JF, McIntyre AD, Alazzam M, Zhao PJ, Dilliott AA, Cao H, Huff MW, Rhainds D, Low-Kam C, Dube MP, Lettre G, Tardif JC, Hegele RA. Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically. Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2439-2445. doi: 10.1161/ATVBAHA.116.308027. Epub 2016 Oct 20.

  PMID: 27765764 BACKGROUND

• Futema M, Bourbon M, Williams M, Humphries SE. Clinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia. Atherosclerosis. 2018 Oct;277:457-463. doi: 10.1016/j.atherosclerosis.2018.06.006.

  PMID: 30270085 BACKGROUND

• Talmud PJ, Shah S, Whittall R, Futema M, Howard P, Cooper JA, Harrison SC, Li K, Drenos F, Karpe F, Neil HA, Descamps OS, Langenberg C, Lench N, Kivimaki M, Whittaker J, Hingorani AD, Kumari M, Humphries SE. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet. 2013 Apr 13;381(9874):1293-301. doi: 10.1016/S0140-6736(12)62127-8. Epub 2013 Feb 22.

  PMID: 23433573 BACKGROUND

• Rimbert A, Daggag H, Lansberg P, Buckley A, Viel M, Kanninga R, Johansson L, Dullaart RPF, Sinke R, Al Tikriti A, Kuivenhoven JA, Barakat MT. Low Detection Rates of Genetic FH in Cohort of Patients With Severe Hypercholesterolemia in the United Arabic Emirates. Front Genet. 2022 Jan 3;12:809256. doi: 10.3389/fgene.2021.809256. eCollection 2021.

  PMID: 35047021 BACKGROUND

• Bamimore MA, Zaid A, Banerjee Y, Al-Sarraf A, Abifadel M, Seidah NG, Al-Waili K, Al-Rasadi K, Awan Z. Familial hypercholesterolemia mutations in the Middle Eastern and North African region: a need for a national registry. J Clin Lipidol. 2015 Mar-Apr;9(2):187-94. doi: 10.1016/j.jacl.2014.11.008. Epub 2014 Nov 29.

  PMID: 25911074 BACKGROUND

Related Links

• The Human Genome Project Completion: Frequently Asked Questions.
• Catalog of Published Genome-Wide Association Studies.
• Checklists for improving rigour in qualitative research: a case of the tail wagging the dog?
• The West Midland Familial Hypercholesterolaemia (FH) screening programme: Evaluating the utility of the 12 SNP polygenic risk score (PRS) across ethnic groupings

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type III

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Abdulmajeed BS Alzubaidi, MD

  Abu Dhabi Health Services Co. -SEHA

  PRINCIPAL INVESTIGATOR

• Erik J Koornneef, PHD

  Abu Dhabi Health Services Co. -SEHA

  STUDY DIRECTOR

• Mhy-Lanie Adduru, MD

  Predictiv Care, Inc.

  STUDY DIRECTOR

• Salah Eldin HM Hu, MD

  Abu Dhabi Health Services Co. -SEHA

  STUDY CHAIR

Central Study Contacts

Alina Naeem, MBBS

CONTACT

+97124102534; alnaeem@seha.ae

Mhy-Lanie Adduru, MD

CONTACT

+14088311991; mhy-lanie@predictivcare.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: A randomized controlled clinical trial of whole-genome sequencing.

Study Record Dates

• First Submitted: June 28, 2024
• First Posted: August 2, 2024
• Study Start: July 29, 2024
• Primary Completion: December 15, 2025
• Study Completion (Estimated): July 15, 2026
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR
• Time Frame: 9-12 months
• Access Criteria: Qualified researchers engaged in independent scientific research can request access to trial IPD, which will be provided following the review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact mhy-lanie@predictivcare.com.

Locations

AE (1)