- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04526457
Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia (IFIGhTFH)
December 9, 2020 updated by: University of Pennsylvania
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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
Study Type
Interventional
Enrollment (Actual)
240
Phase
- Not Applicable
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
10 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Standard of Care
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.
|
Randomized to standard of care with lipid testing only.
|
Other: Genetic Testing
Participants with suspected FH (LDL-C greater than 220 mg/dL) or a previous clinical diagnosis of FH randomized to genetic testing
|
Randomized to genetic testing.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of probands with relatives enrolled
Time Frame: 52 weeks after genetic/lipid testing results are returned to probands
|
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
Time Frame: 52 weeks after results are 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
Time Frame: 52 weeks after results are 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
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proband perceptions about their high cholesterol including its etiology, management and heritability at 20 weeks after enrollment compared to baseline
Time Frame: 20 weeks after enrollment
|
Proband perceptions about their high cholesterol including its etiology, management and heritability were examined at baseline and 20 weeks after enrollment, using a questionnaire administered at these time points.
Investigators examined proband agreement/disagreement with statements about the etiology of their high cholesterol, its management and heritability in these questionnaires.
Using this approach, investigators were able to determine the proportion of probands that agreed/disagreed with these statements, and could compare how these proportions differed between the groups of interest at baseline/follow-up and how these changed from baseline to follow-up.
|
20 weeks after enrollment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Daniel J Rader, MD, University of Pennsylvania
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-90a. doi: 10.1093/eurheartj/eht273. Epub 2013 Aug 15. Erratum In: Eur Heart J. 2020 Dec 14;41(47):4517.
- Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934. doi: 10.1016/j.jacc.2013.11.002. Epub 2013 Nov 12. No abstract available. Erratum In: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. J Am Coll Cardiol. 2015 Dec 22;66(24):2812.
- Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012 Nov;97(11):3956-64. doi: 10.1210/jc.2012-1563. Epub 2012 Aug 14. Erratum In: J Clin Endocrinol Metab. 2014 Dec;99(12):4758-9.
- Wald DS, Bangash FA, Bestwick JP. Prevalence of DNA-confirmed familial hypercholesterolaemia in young patients with myocardial infarction. Eur J Intern Med. 2015 Mar;26(2):127-30. doi: 10.1016/j.ejim.2015.01.014. Epub 2015 Feb 11.
- Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, Baum SJ, Bourbon M, Carrie A, Cuchel M, de Ferranti SD, Defesche JC, Freiberger T, Hershberger RE, Hovingh GK, Karayan L, Kastelein JJP, Kindt I, Lane SR, Leigh SE, Linton MF, Mata P, Neal WA, Nordestgaard BG, Santos RD, Harada-Shiba M, Sijbrands EJ, Stitziel NO, Yamashita S, Wilemon KA, Ledbetter DH, Rader DJ; Convened by the Familial Hypercholesterolemia Foundation. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018 Aug 7;72(6):662-680. doi: 10.1016/j.jacc.2018.05.044.
- Abul-Husn NS, Manickam K, Jones LK, Wright EA, Hartzel DN, Gonzaga-Jauregui C, O'Dushlaine C, Leader JB, Lester Kirchner H, Lindbuchler DM, Barr ML, Giovanni MA, Ritchie MD, Overton JD, Reid JG, Metpally RP, Wardeh AH, Borecki IB, Yancopoulos GD, Baras A, Shuldiner AR, Gottesman O, Ledbetter DH, Carey DJ, Dewey FE, Murray MF. Genetic identification of familial hypercholesterolemia within a single U.S. health care system. Science. 2016 Dec 23;354(6319):aaf7000. doi: 10.1126/science.aaf7000.
- Mortensen MB, Kulenovic I, Klausen IC, Falk E. Familial hypercholesterolemia among unselected contemporary patients presenting with first myocardial infarction: Prevalence, risk factor burden, and impact on age at presentation. J Clin Lipidol. 2016 Sep-Oct;10(5):1145-1152.e1. doi: 10.1016/j.jacl.2016.06.002. Epub 2016 Jun 14.
- De Backer G, Besseling J, Chapman J, Hovingh GK, Kastelein JJ, Kotseva K, Ray K, Reiner Z, Wood D, De Bacquer D; EUROASPIRE Investigators. Prevalence and management of familial hypercholesterolaemia in coronary patients: An analysis of EUROASPIRE IV, a study of the European Society of Cardiology. Atherosclerosis. 2015 Jul;241(1):169-75. doi: 10.1016/j.atherosclerosis.2015.04.809. Epub 2015 Apr 30.
- Pang J, Poulter EB, Bell DA, Bates TR, Jefferson VL, Hillis GS, Schultz CJ, Watts GF. Frequency of familial hypercholesterolemia in patients with early-onset coronary artery disease admitted to a coronary care unit. J Clin Lipidol. 2015 Sep-Oct;9(5):703-8. doi: 10.1016/j.jacl.2015.07.005. Epub 2015 Jul 18.
- Programme WHOHG. Familial hypercholesterolaemia (FH) : report of a second WHO consultation, Geneva, 4 September 1998. 1999:This report is dedicated to the memory of Professo.
- CDC. Genomic tests by levels of evidence. Centers for Disease Control Office of Public Health Genomics. http://www.cdc.gov/genomics/gtesting/file/print/tier.pdf. Published 2013. Accessed August 23, 2016.
- Knowles JW, Rader DJ, Khoury MJ. Cascade Screening for Familial Hypercholesterolemia and the Use of Genetic Testing. JAMA. 2017 Jul 25;318(4):381-382. doi: 10.1001/jama.2017.8543. No abstract available.
- Umans-Eckenhausen MA, Defesche JC, Sijbrands EJ, Scheerder RL, Kastelein JJ. Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands. Lancet. 2001 Jan 20;357(9251):165-8. doi: 10.1016/S0140-6736(00)03587-X.
- Leren TP, Finborud TH, Manshaus TE, Ose L, Berge KE. Diagnosis of familial hypercholesterolemia in general practice using clinical diagnostic criteria or genetic testing as part of cascade genetic screening. Community Genet. 2008;11(1):26-35. doi: 10.1159/000111637. Epub 2008 Jan 15.
- Nherera L, Marks D, Minhas R, Thorogood M, Humphries SE. Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies. Heart. 2011 Jul;97(14):1175-81. doi: 10.1136/hrt.2010.213975.
- deGoma EM, Ahmad ZS, O'Brien EC, Kindt I, Shrader P, Newman CB, Pokharel Y, Baum SJ, Hemphill LC, Hudgins LC, Ahmed CD, Gidding SS, Duffy D, Neal W, Wilemon K, Roe MT, Rader DJ, Ballantyne CM, Linton MF, Duell PB, Shapiro MD, Moriarty PM, Knowles JW. Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry. Circ Cardiovasc Genet. 2016 Jun;9(3):240-9. doi: 10.1161/CIRCGENETICS.116.001381. Epub 2016 Mar 24.
- Ajufo E, deGoma EM, Raper A, Yu KD, Cuchel M, Rader DJ. A randomized controlled trial of genetic testing and cascade screening in familial hypercholesterolemia. Genet Med. 2021 Sep;23(9):1697-1704. doi: 10.1038/s41436-021-01192-z. Epub 2021 May 26.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 1, 2014
Primary Completion (Actual)
December 1, 2016
Study Completion (Actual)
April 1, 2017
Study Registration Dates
First Submitted
August 19, 2020
First Submitted That Met QC Criteria
August 24, 2020
First Posted (Actual)
August 25, 2020
Study Record Updates
Last Update Posted (Actual)
December 10, 2020
Last Update Submitted That Met QC Criteria
December 9, 2020
Last Verified
December 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 820969
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
IRB approval to share IPD was not obtained for this protocol at the time of the initial protocol submission.
If this should be required as part of the peer review process, or after publication of the study results and application will be submitted for a protocol amendment to fulfill this request
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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