Familial Hypercholesterolemia - HeterozygousCHOLCOEURNCT02517944
MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA (CHOLCOEUR)
An observational study of Familial Hypercholesterolemia - Heterozygous, run by Institute of Cardiometabolism and Nutrition, France at 1 site in France.
Trial summary
Patients with familial hypercholesterolemia (FH) at high cardiovascular risk may suffer from silent micro-infarctions (MI) before clinical coronary heart disease manifestations because of the lifetime exposure to elevated serum LDL-cholesterol levels. Read more about this study
- Who is it for?
- Ages 40 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Familial Hypercholesterolemia - Heterozygous
- How many people
- 110 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2014to Nov 2015
- How long will I take part?
- 4 Weeks
- 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 40 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: 110 subjects divided into: * 75 patients with heterozygous form at high cardiovascular risk * 35 controls patients without dyslipidaemia
Who may be able to join
- For patients with heterozygous form of familial hypercholesterolemia:
- Aged between 40 and 60 years
- With an identified genetic mutation (LDL-R, ApoB, PCSK9)
- Asymptomatic,
- With no EKG sign of ischemia
- No personal history of coronary heart disease.
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- Treated or untreated by lipid lowering treatment
- High cardiovascular risk identified by 1 of the following criteria:
- 1. Current smoking (1 cigarette a day) 2 Family history of very premature onset CHD: first- or second-degree male relative onset before age 45, first- or second-degree female relative onset before age 55 3.Two or more cardiovascular risk factors among this list: increasing age (men > 30, women > 40 years of age), LDL-C > 250 mg/dL, male sex, family history of premature onset CHD, first-degree male relative onset before age 55, first-degree female relative onset before age 65, metabolic syndrome, HDL-C < 40 mg/dL, hypertension (BP > 140/or > 90 mmHg or drug treatment), Lp (a) ≥ 50 mg/dL, tendon xanthoma
- For control subjects:
- Aged between 40 and 60 years
- With a normal lipid profile (LDL-C < 1.6g/L HDL-C > 0,45g/L and TG < 4g/L) and untreated by any lipid lowering therapies
- Asymptomatic,
- With EKG showing normal sinus rhythm , no sign of ischemia nor Left Bundle Branch Block
- No personal history of coronary heart disease.
- Control subjects will be matched for age/gender/smoking status and blood pressure
Who cannot join
- Non-affiliation to a healthcare system
- Consent refusal
- Contra-indication to MRI or to gadolinium injection.
- Claustrophobia, metallic devices, pacemaker, mechanical valve implanted before 1985, pregnancy, nursing
- Renal failure
- Technical contra-indication: patient diameter > 70 cm weight > 250 kg
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- Personal history of cardiovascular disease and myocardial infarction
- Diabetes mellitus
- Uncontrolled hypertension
- TG < 4 g/L
- Previous use of an Amgen product in the past 12 months
Trial locations and contacts
1 site in 1 country.
Aurélie RABIER contact
France1 site, 1 recruiting
- Recruiting
Unité de prévention des maladies cardiovasculaires- Unité INSERM 939 Pôle Cardiologie/Métabolisme Groupe Hospitalier Pitié-Salpêtrière
Paris, 75013
David Rosenbaum, MD, david.rosenbaum@psl.aphp.fr
Eric Bruckert, Pr, eric.bruckert@psl.aphp.fr
About this study
Official title: MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA
Patients with familial hypercholesterolemia (FH) at high cardiovascular risk may suffer from silent micro-infarctions (MI) before clinical coronary heart disease manifestations because of the lifetime exposure to elevated serum LDL-cholesterol levels.
The study aims to demonstrate the higher prevalence of silent myocardial infarction in a population of asymptomatic patients with familial hypercholesterolemia at high cardiovascular risk in comparison to control patients using Cardiac Magnetic Resonance sequences of delayed gadolinium enhancement.
Read the detailed description
To demonstrate the higher prevalence of silent myocardial infarction in a population of asymptomatic patients with familial hypercholesterolemia at high cardiovascular risk in comparison to control patients, the protocol is the following:
- to enroll 75 patients with familial hypercholesterolemia (FH)
- to enroll 35 subjects without FH (control group)
- for each subject, to collect data from his medical file (blood test results) and to perform a cardiac and aortic MRI in order to evaluate the micro-infarction proportion.
The study will be performed according to GCPs and with respect with french laws.
- Keywords
- Familial hypercholesterolemia
- Medical subject headings
- Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Familial hypercholesterolemia patients | * clinical data * biological data * cardiac and aortic RMI with gadolinium | |
| Control group | * clinical data * biological data * cardiac and aortic RMI with gadolinium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients presenting with at least one micro infarction at RMI
Cardiac and aortic RMI with gadolinium
Measured: Within 4 weeks after consent signature
Secondary outcomes (3)
LDL-Cholesterol burden (compared to standard values)
Measured: The most recent value within the last 5 years.
Anatomic and functional indexes of the aorta (maximal and minimal areas of aortic lumen, aortic flow)
Measured: Within 4 weeks after consent signature
Correlations between LDL-Cholesterol burden & presence of micro infarction, between LDL-Cholesterol burden & myocardial fibrosis, and between LDL-Cholesterol burden & aortic stiffness indexes
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2015 (estimated)
- Study startNov 2014
- Primary completionSep 2015 (estimated)
- Study completionNov 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Familial Hypercholesterolemia - HeterozygousStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 110 participants (estimated)
- Target duration
- 4 Weeks
Sponsor and investigators
- Lead sponsor
- Institute of Cardiometabolism and Nutrition, France
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- David Rosenbaum, MD, Principal investigator, Study principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02517944
- Sponsor's protocol ID
- 14DRM_CHOLCOEUR
- Acronym
- CHOLCOEUR
- Status last verified
- Jul 2015
- First submitted
- 14 Jan 2015
- Last updated
- 7 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Hovingh GK, Davidson MH, Kastelein JJ, O'Connor AM. Diagnosis and treatment of familial hypercholesterolaemia. Eur Heart J. 2013 Apr;34(13):962-71. doi: 10.1093/eurheartj/eht015. Epub 2013 Feb 14.
PubMed 23416791Nemati MH, Astaneh B. Optimal management of familial hypercholesterolemia: treatment and management strategies. Vasc Health Risk Manag. 2010 Dec 3;6:1079-88. doi: 10.2147/VHRM.S8283.
PubMed 21191428Descamps OS, Gilbeau JP, Leysen X, Van Leuven F, Heller FR. Impact of genetic defects on atherosclerosis in patients suspected of familial hypercholesterolaemia. Eur J Clin Invest. 2001 Nov;31(11):958-65. doi: 10.1046/j.1365-2362.2001.00915.x.
PubMed 11737238Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol. 2004 Sep 1;160(5):421-9. doi: 10.1093/aje/kwh237.
PubMed 15321838Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ. 1991 Oct 12;303(6807):893-6. doi: 10.1136/bmj.303.6807.893.
PubMed 1933004Kroon AA, Ajubi N, van Asten WN, Stalenhoef AF. The prevalence of peripheral vascular disease in familial hypercholesterolaemia. J Intern Med. 1995 Nov;238(5):451-9. doi: 10.1111/j.1365-2796.1995.tb01223.x.
PubMed 7595185Kolansky DM, Cuchel M, Clark BJ, Paridon S, McCrindle BW, Wiegers SE, Araujo L, Vohra Y, Defesche JC, Wilson JM, Rader DJ. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol. 2008 Dec 1;102(11):1438-43. doi: 10.1016/j.amjcard.2008.07.035. Epub 2008 Sep 11.
PubMed 19026292Benn 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.
PubMed 22893714Farnier M, Bruckert E. Severe familial hypercholesterolaemia: current and future management. Arch Cardiovasc Dis. 2012 Dec;105(12):656-65. doi: 10.1016/j.acvd.2012.05.011. Epub 2012 Oct 6.
PubMed 23199621Vilahur G, Casani L, Juan-Babot O, Guerra JM, Badimon L. Infiltrated cardiac lipids impair myofibroblast-induced healing of the myocardial scar post-myocardial infarction. Atherosclerosis. 2012 Oct;224(2):368-76. doi: 10.1016/j.atherosclerosis.2012.07.003. Epub 2012 Jul 22.
PubMed 22882904Kaufmann PA, Gnecchi-Ruscone T, Schafers KP, Luscher TF, Camici PG. Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol. 2000 Jul;36(1):103-9. doi: 10.1016/s0735-1097(00)00697-5.
PubMed 10898420Dayanikli F, Grambow D, Muzik O, Mosca L, Rubenfire M, Schwaiger M. Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography. Circulation. 1994 Aug;90(2):808-17. doi: 10.1161/01.cir.90.2.808.
PubMed 8044952Giulia Gagliardi M, Crea F, Polletta B, Bassano C, La Vigna G, Ballerini L, Ragonese P. Coronary microvascular endothelial dysfunction in transplanted children. Eur Heart J. 2001 Feb;22(3):254-60. doi: 10.1053/euhj.2001.2105.
PubMed 11161937Watts GF, Sullivan DR, Poplawski N, van Bockxmeer F, Hamilton-Craig I, Clifton PM, O'Brien R, Bishop W, George P, Barter PJ, Bates T, Burnett JR, Coakley J, Davidson P, Emery J, Martin A, Farid W, Freeman L, Geelhoed E, Juniper A, Kidd A, Kostner K, Krass I, Livingston M, Maxwell S, O'Leary P, Owaimrin A, Redgrave TG, Reid N, Southwell L, Suthers G, Tonkin A, Towler S, Trent R; Familial Hypercholesterolaemia Australasia Network Consensus Group (Australian Atherosclerosis Society). Familial hypercholesterolaemia: a model of care for Australasia. Atheroscler Suppl. 2011 Oct;12(2):221-63. doi: 10.1016/j.atherosclerosissup.2011.06.001. Epub 2011 Sep 13.
PubMed 21917530De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Cats VM, Orth-Gomer K, Perk J, Pyorala K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D; European Society of Cardiology. American Heart Association. American College of Cardiology. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts). Atherosclerosis. 2004 Apr;173(2):381-91. No abstract available.
PubMed 15195638
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA
- ClinicalTrials.gov ID
- NCT02517944
- Acronym / sponsor ID
- CHOLCOEUR / 14DRM_CHOLCOEUR
- Keywords
- Familial hypercholesterolemia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Institute of Cardiometabolism and Nutrition, FranceUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Nov 2014
- Primary completion
- Sep 2015 (estimated)
- Study completion
- Nov 2015 (estimated)
- First posted
- 7 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with familial hypercholesterolemia (FH) at high cardiovascular risk may suffer from silent micro-infarctions (MI) before clinical coronary heart disease manifestations because of the lifetime exposure to elevated serum LDL-cholesterol levels.
The study aims to demonstrate the higher prevalence of silent myocardial infarction in a population of asymptomatic patients with familial hypercholesterolemia at high cardiovascular risk in comparison to control patients using Cardiac Magnetic Resonance sequences of delayed gadolinium enhancement.
Detailed description
To demonstrate the higher prevalence of silent myocardial infarction in a population of asymptomatic patients with familial hypercholesterolemia at high cardiovascular risk in comparison to control patients, the protocol is the following:
- to enroll 75 patients with familial hypercholesterolemia (FH)
- to enroll 35 subjects without FH (control group)
- for each subject, to collect data from his medical file (blood test results) and to perform a cardiac and aortic MRI in order to evaluate the micro-infarction proportion.
The study will be performed according to GCPs and with respect with french laws.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 4 Weeks
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Familial hypercholesterolemia patients | – | –* clinical data * biological data * cardiac and aortic RMI with gadolinium |
| Control group | – | –* clinical data * biological data * cardiac and aortic RMI with gadolinium |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- 110 subjects divided into: * 75 patients with heterozygous form at high cardiovascular risk * 35 controls patients without dyslipidaemia
Key inclusion criteria (16 listed)
- Aged between 40 and 60 years
- With an identified genetic mutation (LDL-R, ApoB, PCSK9)
- Asymptomatic,
- With no EKG sign of ischemia
- No personal history of coronary heart disease.
Key exclusion criteria (11 listed)
- Non-affiliation to a healthcare system
- Consent refusal
- Contra-indication to MRI or to gadolinium injection.
- Claustrophobia, metallic devices, pacemaker, mechanical valve implanted before 1985, pregnancy, nursing
- Renal failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Percentage of patients presenting with at least one micro infarction at RMI
Time frame: Within 4 weeks after consent signature
Cardiac and aortic RMI with gadolinium
3 secondary outcomes
LDL-Cholesterol burden (compared to standard values)
Time frame: The most recent value within the last 5 years.
Anatomic and functional indexes of the aorta (maximal and minimal areas of aortic lumen, aortic flow)
Time frame: Within 4 weeks after consent signature
Correlations between LDL-Cholesterol burden & presence of micro infarction, between LDL-Cholesterol burden & myocardial fibrosis, and between LDL-Cholesterol burden & aortic stiffness indexes
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2015.
- Background: PubMed 23416791Hovingh GK, Davidson MH, Kastelein JJ, O'Connor AM. Diagnosis and treatment of familial hypercholesterolaemia. Eur Heart J. 2013 Apr;34(13):962-71. doi: 10.1093/eurheartj/eht015. Epub 2013 Feb 14.
- Background: PubMed 21191428Nemati MH, Astaneh B. Optimal management of familial hypercholesterolemia: treatment and management strategies. Vasc Health Risk Manag. 2010 Dec 3;6:1079-88. doi: 10.2147/VHRM.S8283.
- Background: PubMed 11737238Descamps OS, Gilbeau JP, Leysen X, Van Leuven F, Heller FR. Impact of genetic defects on atherosclerosis in patients suspected of familial hypercholesterolaemia. Eur J Clin Invest. 2001 Nov;31(11):958-65. doi: 10.1046/j.1365-2362.2001.00915.x.
- Background: PubMed 15321838Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol. 2004 Sep 1;160(5):421-9. doi: 10.1093/aje/kwh237.
- Background: PubMed 1933004Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ. 1991 Oct 12;303(6807):893-6. doi: 10.1136/bmj.303.6807.893.
- Background: PubMed 7595185Kroon AA, Ajubi N, van Asten WN, Stalenhoef AF. The prevalence of peripheral vascular disease in familial hypercholesterolaemia. J Intern Med. 1995 Nov;238(5):451-9. doi: 10.1111/j.1365-2796.1995.tb01223.x.
- Background: PubMed 19026292Kolansky DM, Cuchel M, Clark BJ, Paridon S, McCrindle BW, Wiegers SE, Araujo L, Vohra Y, Defesche JC, Wilson JM, Rader DJ. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol. 2008 Dec 1;102(11):1438-43. doi: 10.1016/j.amjcard.2008.07.035. Epub 2008 Sep 11.
- Background: PubMed 22893714Benn 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.
- Background: PubMed 23199621Farnier M, Bruckert E. Severe familial hypercholesterolaemia: current and future management. Arch Cardiovasc Dis. 2012 Dec;105(12):656-65. doi: 10.1016/j.acvd.2012.05.011. Epub 2012 Oct 6.
- Background: PubMed 22882904Vilahur G, Casani L, Juan-Babot O, Guerra JM, Badimon L. Infiltrated cardiac lipids impair myofibroblast-induced healing of the myocardial scar post-myocardial infarction. Atherosclerosis. 2012 Oct;224(2):368-76. doi: 10.1016/j.atherosclerosis.2012.07.003. Epub 2012 Jul 22.
- Background: PubMed 10898420Kaufmann PA, Gnecchi-Ruscone T, Schafers KP, Luscher TF, Camici PG. Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol. 2000 Jul;36(1):103-9. doi: 10.1016/s0735-1097(00)00697-5.
- Background: PubMed 8044952Dayanikli F, Grambow D, Muzik O, Mosca L, Rubenfire M, Schwaiger M. Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography. Circulation. 1994 Aug;90(2):808-17. doi: 10.1161/01.cir.90.2.808.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aurélie RABIER contact
David Rosenbaum, MD principal investigator
Study principal investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Familial Hypercholesterolemia - Heterozygous, run by Institute of Cardiometabolism and Nutrition, France at 1 site in France.
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 16 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 7 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aurélie RABIER (a.rabier@ican-institute.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients presenting with at least one micro infarction at RMI (time frame: Within 4 weeks after consent signature). 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 NCT02517944, which also lists 28 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 7 Aug 2015.