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Genetic Causes of Hypercholesterolaemia in the Emirati Population

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ClinicalTrials.gov Identifier: NCT03597958
Recruitment Status : Recruiting
First Posted : July 24, 2018
Last Update Posted : February 27, 2019
Sponsor:
Information provided by (Responsible Party):
Imperial College London Diabetes Centre

Brief Summary:
The scientific aims of the project are to understand the genetic basis of Familial Hypercholesterolaemia (FH) in the Emirati population and estimate the overall prevalence of the disease. In addition, a clinical aim of the project is to explore the effectiveness of screening the relatives of individuals affected by FH and other lipid disorders ("cascade" screening) within Emirati families.

Condition or disease Intervention/treatment
Familial Hypercholesterolemia Genetic: Next generation sequencing (NGS)

Detailed Description:

Familial Hypercholesterolaemia is an inherited genetic disorder which causes elevated levels of low density lipoprotein (LDL) cholesterol in the blood. High LDL is a risk factor for with arterial disease and people with FH develop coronary artery disease (CAD) early in life. People with only one inherited copy of the defective gene usually develop CAD before the age of 60, whereas individuals who have inherited two copies usually die before the age of 30 from myocardial infarction ("heart attack") or sudden cardiac death. Coronary artery disease is a major cause of death and disability in the United Arab Emirates (UAE), and the medical costs associated with treating this condition are significant. Early identification and treatment of affected individuals can substantially postpone the onset of arterial disease and reduce the risk of mortality. In clinical practice, FH cases are usually identified by screening the relatives of people known to be affected.

Current study will focus on identifying individuals with high risk score for FH, based on the available medical records and laboratory information system (LIS). Furthermore, patients with history of premature ischaemic vascular disease and/or high readings for LDL-C will be approached and asked to participate.

The scientific aims of the study are:

  • Identifying individuals with likelihood of FH diagnosis and confirming FH by genetic testing (applying Next Generation Sequencing NGS technology to analyse the genes already known and/or suspected to cause FH).
  • Identifying novel FH genes and mutations in the Emirati population by performing whole exome and whole genome sequencing
  • Validating positive genetic test results by performing mutational analysis on parental samples (if available)
  • Introducing cascade screening on a clinical basis in order to identify affected relatives of those index individuals with a clinical diagnosis of FH
  • Determining the prevalence of FH in the UAE
  • Determining the short and the long-term clinical outcomes of FH in the UAE

It is expected that the cascade screening will provide additional clinical benefit to study participants and their families in terms of early identification and treatment where diagnosis could otherwise be missed. Early recognition and treatment in individuals with FH has been shown to reduce morbidity and mortality of affected individuals. The information gathered during this project will help introduce a cost-effective method for identifying people with dyslipidaemias and provide early intervention and management.


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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Genetic Causes of Hypercholesterolaemia in the Emirati Population
Actual Study Start Date : January 17, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Hypercholesterolaemia

Individuals attending Imperial College London Diabetes Centre (ICLDC) and with LDL-C ≥5.0 mmol/L, for children <18 years LDL-C>95th centile by age and gender for country, and possible evidence of known premature CHD.

Individuals with a high probability of disease according to the Dutch Lipid Network Criteria, score of ≥6 points, will be identified as possible probands (individual serving as our starting point for the genetic study of the family) and will be selected for further screening.

Patients will be tested for known and/or suspected FH genes, using next generation sequencing (NGS) panel, whole exome and/or whole genome sequencing (WES/WGS) in cases where FH is highly suspected despite negative results from panel testing, and transcriptomic analysis of RNA blood samples.

Genetic: Next generation sequencing (NGS)
NGS panel, whole exome / genome sequencing (WES/WGS), transcriptome analysis




Primary Outcome Measures :
  1. Next generation sequencing (NGS) [ Time Frame: through study completion, an average of 2 year ]
    Identify individuals with likelihood of FH diagnosis and confirming FH by genetic testing (applying NGS technology to analyse the genes already known and/or suspected to cause FH).Identifying novel FH genes and mutations in the Emirati population by performing whole exome and whole genome sequencing (WES/WGS).


Secondary Outcome Measures :
  1. Genetic test validation [ Time Frame: through study completion, an average of 2 year ]
    Validating positive genetic test results by performing mutational analysis on parental samples (if available)

  2. Cascade screening [ Time Frame: through study completion, an average of 2 year ]
    Introduce cascade screening on a clinical basis in order to identify affected relatives of those index individuals with a clinical diagnosis of FH

  3. Prevalence of FH [ Time Frame: through study completion, an average of 2 year ]
    Determine the prevalence of FH in the UAE


Biospecimen Retention:   Samples With DNA
DNA will be extracted from collected blood samples for genetic analysis


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Patients with hypercholesterolaemia attending Imperial College London Diabetes Centre, UAE.
Criteria

Inclusion Criteria:

  • Patients attending Imperial College London Diabetes Centre
  • Patients with hypercholesterolaemia
  • Patients with possible evidence of known premature coronary heart disease (CHD)
  • Patients (or parent/legal guardian if <18 years) willing and able to give informed consent for participation in the study.

Exclusion Criteria:

  • Patients with no history of hypercholesterolaemia
  • Patients or their legal guardian/legal representative who are unwilling or unable to give informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03597958


Contacts
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Contact: Hinda Daggag, PhD +971 2 404 0800 hdaggag@icldc.ae

Locations
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United Arab Emirates
Imperial College London Diabetes Centre Recruiting
Abu Dhabi, United Arab Emirates, 48338
Contact: Hinda Daggag, PhD    +971 2 404 0800    hdaggag@icldc.ae   
Sponsors and Collaborators
Imperial College London Diabetes Centre
Investigators
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Principal Investigator: Maha Barakat, PhD FRCP Imperial College London Diabetes Centre

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Responsible Party: Imperial College London Diabetes Centre
ClinicalTrials.gov Identifier: NCT03597958     History of Changes
Other Study ID Numbers: IREC027
First Posted: July 24, 2018    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: February 2019
Keywords provided by Imperial College London Diabetes Centre:
Familial Hypercholesterolemia
Hypercholesterolemia
Cascade Screening
Novel FH Genes
Novel FH Mutations
Next generation sequencing
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias