AzTrials
AzTrials

Familial HypercholesterolemiaRAVENCT03640234

Return of Actionable Variants Empirical Study

An observational study of Familial Hypercholesterolemia, run by Mayo Clinic.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a genomic implementation project with ancillary studies to understand the impact on patients' health and well-being of returning genomic results to them and depositing those results in the medical record. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Familial Hypercholesterolemia
How many people
418 participants
Where
No sites listed yet
Study dates
25 Feb 2016to 1 Sep 2022
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: We recruited 3030 participants from Mayo Clinic biobanks in Rochester, MN, who had hypercholesterolemia, colon polyps or both, thereby enriching for FH.

Who may be able to join

  • Moderate to Severe Hypercholesterolemia, elevated triglycerides, or colon polyps
  • Resident of southeast Minnesota area
  • Able to provide informed consent
  • Current participant in the Mayo Clinic Biobank (08-007049, Cerhan PI), the Vascular Disease Biorepository (08-008355, Kullo PI), or the Study of the Genetic Determinants of Peripheral Artery Disease (PAD) (06-002911, Kullo PI) with blood derived DNA available

Who cannot join

  • Pregnant women will be allowed to enroll in the study. This is not an interventional study and there will be no risk to the mother or neonate. Other vulnerable study populations will be excluded.

About this study

Official title: Return of Actionable Variants Empirical (RAVE) Study

This is a genomic implementation project with ancillary studies to understand the impact on patients' health and well-being of returning genomic results to them and depositing those results in the medical record.

Read the detailed description

Study participant DNA samples will be sequenced for 109 genes of interest along with genotyping of select polymorphisms. Genetic tests will be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified lab (Baylor Human Genome Sequencing Laboratory). Selected results (pathogenic/likely pathogenic) will be returned to participants by a genetic counselor and deposited into the Electronic Health Record (EHR).

Medical subject headings
Hyperlipoproteinemia Type II

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Participant utilization of clinical resources following the return of medically actionable genetic variants.

    The EHR of study participants will be periodically reviewed beginning 6 months following the disclosure of results. EHR documented utilization of clinical resources by participants (e.g. lipid profile for cholesterol measurement, mammogram, colonoscopy, prophylactic surgery, etc.) will be reviewed to assess whether the disclosure of actionable genetic findings led to initiation of medical therapy or ordering of additional tests. Data will be manually abstracted into condition-specific REDCap questionnaires which are harmonized across multiple eMERGE Network sites.

    Measured: Feb 2016-June 2020

Secondary outcomes (5)

  1. The number of new cases detected as a result of cascade screening in the family members

    This outcome is being assessed as a supplemental study that includes patients with definite, probable and possible Familial Hypercholesterolemia (FH). We will compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. We will enroll 50 patients with definite FH by recruiting an additional 25 from the FH Clinic at Mayo and 50 patients each with probable and possible FH, matching on age and sex. Family members of patients with definite FH will undergo testing for the relevant pathogenic variant using saliva kits and family members of those with probable/possible FH will have a lipid profile checked. We will assess the number of new cases detected (defined as presence of a pathogenic variant in the family member of definite FH patient or LDL-C >155 mg/dL (>130 mg/dL in children) in family members of probable/possible FH patients, and the cost of detecting a new case.

    Measured: Feb 2017- Dec 2020

  2. Total Expense due to disclosure of actionable variants

    The EHR will be periodically reviewed after disclosure of results to assess whether the disclosure led to initiation of medical therapy or ordering of additional tests. Measured in U.S. dollars.

    Measured: 4 years

  3. Participant intent-to-share genetic test results

    Participants are offered pre-and-post-counseling questionnaires, provide pedigree information, and family member contact information. Questionnaires include measures of intent-to-share and barriers to sharing genetic results.

    Measured: Sept 2017-June 2020

  4. Number of first-degree relatives per proband and number of contacted first-degree relatives per proband

    The number of first-degree relatives will be assessed using patient-provided family history information. The number of contacted family members will be assessed by measuring family member response to participant contact materials.

    Measured: Sept 2017-Dec 2020

  5. Family member uptake of genetic testing

    Family member respondents who provide consent will be offered genetic testing. The uptake of genetic testing will be documented for each family member.

    Measured: Sept 2017- Dec 2020

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2018
  2. Study start25 Feb 2016
  3. Primary completion1 Sep 2022
  4. Study completion1 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Other
Time perspective
Prospective
Enrolment
418 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03640234
Sponsor's protocol ID
15-005013
Other IDs
U01HG006379
Acronym
RAVE
Status last verified
Sep 2022
First submitted
23 Jul 2018
Last updated
27 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kaphingst KA, McBride CM, Wade C, Alford SH, Reid R, Larson E, Baxevanis AD, Brody LC. Patients' understanding of and responses to multiplex genetic susceptibility test results. Genet Med. 2012 Jul;14(7):681-7. doi: 10.1038/gim.2012.22.

    PubMed 22481132

  • Brehaut JC, O'Connor AM, Wood TJ, Hack TF, Siminoff L, Gordon E, Feldman-Stewart D. Validation of a decision regret scale. Med Decis Making. 2003 Jul-Aug;23(4):281-92. doi: 10.1177/0272989X03256005.

    PubMed 12926578

  • Zick CD, Mathews CJ, Roberts JS, Cook-Deegan R, Pokorski RJ, Green RC. Genetic testing for Alzheimer's disease and its impact on insurance purchasing behavior. Health Aff (Millwood). 2005 Mar-Apr;24(2):483-90. doi: 10.1377/hlthaff.24.2.483.

    PubMed 15757934

  • Dunlay SM, Shah ND, Shi Q, Morlan B, VanHouten H, Long KH, Roger VL. Lifetime costs of medical care after heart failure diagnosis. Circ Cardiovasc Qual Outcomes. 2011 Jan 1;4(1):68-75. doi: 10.1161/CIRCOUTCOMES.110.957225. Epub 2010 Dec 7.

    PubMed 21139091

  • Lipscomb J, Ancukiewicz M, Parmigiani G, Hasselblad V, Samsa G, Matchar DB. Predicting the cost of illness: a comparison of alternative models applied to stroke. Med Decis Making. 1998 Apr-Jun;18(2 Suppl):S39-56. doi: 10.1177/0272989X98018002S07.

    PubMed 9566466

  • Gaff CL, Clarke AJ, Atkinson P, Sivell S, Elwyn G, Iredale R, Thornton H, Dundon J, Shaw C, Edwards A. Process and outcome in communication of genetic information within families: a systematic review. Eur J Hum Genet. 2007 Oct;15(10):999-1011. doi: 10.1038/sj.ejhg.5201883. Epub 2007 Jul 4.

    PubMed 17609674

  • Hughes C, Lerman C, Schwartz M, Peshkin BN, Wenzel L, Narod S, Corio C, Tercyak KP, Hanna D, Isaacs C, Main D. All in the family: evaluation of the process and content of sisters' communication about BRCA1 and BRCA2 genetic test results. Am J Med Genet. 2002 Jan 15;107(2):143-50. doi: 10.1002/ajmg.10110.

    PubMed 11807889

  • Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD; ASCOT investigators; NORDIL investigators; BRIGHT Consortium. Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. Am J Hum Genet. 2009 Nov;85(5):628-42. doi: 10.1016/j.ajhg.2009.10.014.

    PubMed 19913121

  • Futema M, Shah S, Cooper JA, Li K, Whittall RA, Sharifi M, Goldberg O, Drogari E, Mollaki V, Wiegman A, Defesche J, D'Agostino MN, D'Angelo A, Rubba P, Fortunato G, Walus-Miarka M, Hegele RA, Aderayo Bamimore M, Durst R, Leitersdorf E, Mulder MT, Roeters van Lennep JE, Sijbrands EJ, Whittaker JC, Talmud PJ, Humphries SE. Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries. Clin Chem. 2015 Jan;61(1):231-8. doi: 10.1373/clinchem.2014.231365. Epub 2014 Nov 20.

    PubMed 25414277

  • Miller AA, Bangash H, Smith CY, Wood-Wentz CM, Bailey KR, Kullo IJ. A pragmatic clinical trial of cascade testing for familial hypercholesterolemia. Genet Med. 2022 Dec;24(12):2535-2543. doi: 10.1016/j.gim.2022.08.026. Epub 2022 Sep 29.

    PubMed 36173399

Questions about this trial

What is this clinical trial studying?

An observational study of Familial Hypercholesterolemia, run by Mayo Clinic.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participant utilization of clinical resources following the return of medically actionable genetic variants. (time frame: Feb 2016-June 2020). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03640234, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.

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