Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia

Study Overview
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Brief Summary
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To test the hypothesis that in patients with a clinical diagnosis of familial hypercholesterolemia (FH), genetic testing and identification of a causative mutation might enhance the success of family-based cascade screening.

Detailed Description
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To examine the impact of genetic testing on the efficiency of cascade screening for FH, patients with suspected FH or a clinical diagnosis of FH have been randomized to genetic testing or standard of care with lipid testing alone. After systematic encouragement of family enrollment, as a primary endpoint, the compared the number of probands with relatives enrolled in each group one year after results were returned to probands. The secondary endpoints examined include the number of relatives enrolled within 52 weeks of the genetic counseling call and the number of relatives diagnosed with FH through the study. Exploratory subgroup analyses were conducted stratifying the cohort by randomization/genetic test result. Further exploratory analyses compared probands' perceptions about high cholesterol diagnosis at baseline and at 20 weeks from enrollment

Official Title
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Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia

Conditions
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Hypercholesterolemia, Familial

Intervention / Treatment
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* Other: Standard of Care
* Other: Genetic Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For probands, inclusion criteria are as follows: LDL cholesterol > 220 mg/dL or a previous clinical diagnosis of FH Aged 18 years or older Ability to provide informed consent Willingness/ability to contact a minimum of 2 biological relatives about the study Exclusion Criteria: For family members of probands, inclusion criteria are as follows: Willingness to participate in the study Age 10 or older Ability to give informed consent/assent

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Probands were randomized 2:1 to genetic testing for FH plus lipid testing or lipid testing alone
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard of Care<br>Participants with suspected FH (LDL-C greater than 220 mg/dL) or a previous clinical diagnosis of FH and randomized to standard of care with lipid testing only. | Other: Standard of Care<br>* Randomized to standard of care with lipid testing only.<br>|
| Other: Genetic Testing<br>Participants with suspected FH (LDL-C greater than 220 mg/dL) or a previous clinical diagnosis of FH randomized to genetic testing | Other: Genetic Testing<br>* Randomized to genetic testing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of probands with relatives enrolled | The primary outcome of this study was the number of probands with family members enrolled in the study within 52 weeks of results being returned to probands. Investigators compared the proportion of probands with a relative enrolled in the genetic testing group with the proportion of probands with a relative enrolled in the usual care group (lipid testing only). Relative enrolment was defined as the return of a test kit within the study time frame. | 52 weeks after genetic/lipid testing results are returned to probands | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of relatives enrolled in the study 52 weeks after results were returned to probands | The number of relatives enrolled in the study within 52 weeks of results being returned to probands. Investigators compared the number of relatives enrolled in the genetic testing group with the number of relatives enrolled in the usual care group (lipid testing only). Relative enrolment was defined as the return of a test kit within the study time frame. | 52 weeks after results are returned to probands | 
| The number of family members diagnosed with FH 52 weeks after results were returned to probands | The number of family members diagnosed with FH within 52 weeks of results being returned to probands. Investigators compared the number of enrolled relatives diagnosed with FH in the genetic testing group with the number of enrolled relatives diagnosed with FH in the usual care group (lipid testing only). This diagnosis had to be made through the study. The number of enrolled relatives diagnosed with FH in each group was expressed as the new case per index case ratio (relatives diagnosed with FH/total number of index case). Relative enrolment was defined as the return of a test kit within the study time frame. The diagnosis of FH was based on meeting either genetic or the Make Early Diagnosis To Prevent Early Deaths (MEDPED) clinical criteria | 52 weeks after results are returned to probands | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial Hypercholesterolemia, Genetics, Cascade screening