HypobetalipoproteinemiaHYPOCHOLNCT02354079
HYPOCHOL : A Genetically-based Strategy to Identify New Targets in Cholesterol Metabolism
A study testing hypobetalipoproteinemia genetic and genotypic screening in people with Hypobetalipoproteinemia, run by Nantes University Hospital at 1 site in France.
Trial summary
The aim of this study is to identify new targets in cholesterol metabolism thanks to a genetically-based strategy. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypobetalipoproteinemia
- What is being tested?
- hypobetalipoproteinemia genetic and genotypic screening
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 435 participants
- Where
- 1 siteFrance
- Study dates
- 7 Jan 2016to 7 Jan 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- For index cases without family screening:
- o Patient with HBL: fasting LDL-C ≤ 50 mg/dl.
- For familial affected cases:
- Relative with HBL: fasting LDL-C ≤ 80 mg/dl and/or Apo B ≤ 50 mg/dl and at least one related family case suffering from HBL.
- All subjects, including familial non-affected cases, must give written consent (dated and signed) to participate at the constitution of biobank (including DNA samples and urine samples).
Who cannot join
- Use of lipid-lowering drugs (statins, fibrates, ezetimibe, bile-acid sequestering resin) or nutraceuticals known to affect lipids (red yeast rice, margarine and dairy with plant sterol)
- Patient screened within an extreme metabolic disturbance (emergency situations, sepsis, hospitalization in intensive care unit)
- Patients with hyperthyroidism, severe liver failure, end stage chronic kidney disease, serious pancreatic failure, anemia related to thalassemia or sickle cell disease, strict vegan diet or malnutrition
- Refusal of the patient or his legal representative to participate in the study"
Trial locations and contacts
1 site in 1 country.
About this study
The aim of this study is to identify new targets in cholesterol metabolism thanks to a genetically-based strategy.
Read the detailed description
The goal is to recruit 400 subjects: 200 adult subjects with familial hypobetalipoproteinemia (FHBL) (index cases) plus 200 additional related subjects in at least 10 large informative FHBL families, in which there is no known mutation in FHBL genes.
The patient care is modified: patient will have an Hospital Anxiety and Depression (HAD) questionnaire (focus on depressive syndrome), a food diary, and some additional blood analysis (including genetic analysis).
One of the main issue to recruit FHBL patients is the fact that they are asymptomatic and that FHBL is not identified as a serious illness by their general physicians.
Step-1. Excluding mutations in selected candidate genes As a first approach to screen candidate genes and exclude patients with known mutations, the investigators developed a custom design based on the Haloplex™ technology (Agilent® Technologies) to perform high-throughput sequencing of the coding regions of 10 genes, including those previously described in FHBL (apolipoprotein B (APOB), Proprotein convertase subtilisin/kexin type 9 (PCSK9)), Microsomal triglyceride transfer protein (MTP or ABL), chylomicron retention disease (CMRD), Secretion associated, Ras related GTPase (SARA2 gene), as well as 6 additional candidate genes in cholesterol metabolism (low density lipoprotein receptor (LDLR), Sortilin (SORT1), Inducible Degrader of the LDL receptor (IDOL), Cholesteryl ester transfer protein (CETP), Apolipoprotein E (ApoE) and Angiopoietin-like Protein 3 (ANGTPL3)). All the recruited index cases (n=200) will be genotyped to select only those without mutations in previously described genes, being approximately 50% of our index case cohort.
Step-2. Identification of informative families and exome sequencing In patients without identified mutations, the investigators will conduct a familial screening in order to identify other cases of FHBL among proband relatives. An analysis of fasting plasma lipid parameters (total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Low-Density Lipoproteins (LDL-C) and triglycerides (TG)) will be performed for each related. Affected subjects will be determined by a spontaneous LDL-C < 80 mg/dl and/or apoB < 50 mg/dl. In contrast, non-affected subjects will display LDL-C > 80 mg/dl and/or apoB > 50 mg/dl.
For large families, the investigators will then combine whole-exome sequencing and linkage analysis to identify any novel genetic variant likely explaining FHBL. Depending on family pedigree, whole-exome sequencing (WES) will be performed on 2 to 5 patients per family. All relatives will be genotyped for linkage analysis.
In parallel to this genetic approach, a regional epidemiological analysis will be performed to identify some geographical clusters with a high prevalence of the disease, as developed in the project named VaCaRMe (for Vascular and Cardiac, Respiratory and Metabolic overcome diseases)
An additional aim, based on an exhaustive phenotyping of FHBL patients, is to investigate the safety of very low LDL-C and to perform some genotype-phenotype correlations in patients with FHBL population."
- Conditions
- Hypobetalipoproteinemia
- Being tested
- hypobetalipoproteinemia genetic and genotypic screening
- Keywords
- Low LDL-C, Target Identification, Genetic, Endocrinology, Cardiovascular Disease
- Medical subject headings
- Hypobetalipoproteinemias, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypobetalipoproteinemia genetic and genotypic screeningGenetic
| Study group | Role | What they receive |
|---|---|---|
| genetic analysis | Other | Not described Receives: Genetic: hypobetalipoproteinemia genetic and genotypic screening |
What is being measured
The primary outcome is the main question the study is designed to answer.
type and number of genetic abnormalities leading to FHBL
To identify new gene involved in FHBL and determine genetic cause of FHBL (Patients with FHBL and their relatives will be recruited to establish familial forms of FHBL in large informative families with no mutations in known classical FHBL genes. This will allow perform genetic analysis using new approaches to genetic broadband (exome sequencing analysis + linkage analysis). This approach will allow specify which chromosomal regions are shared only by affected individuals, and identify new candidate genes).
Measured: ten years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study start7 Jan 2016
- Primary completion7 Jan 2022
- Study completion7 Jan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypobetalipoproteinemiaStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 435 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charlotte AUTHIER, Doctor, Principal investigator, Health Care Centers of French Health Insurance in Saint-NazaireDidier GOXE, Principal investigator, Health Care Centers of French Health Insurance in La Roche sur Yon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02354079
- Sponsor's protocol ID
- RC14_0400
- Acronym
- HYPOCHOL
- Status last verified
- Apr 2026
- First submitted
- 14 Jan 2015
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HYPOCHOL : A Genetically-based Strategy to Identify New Targets in Cholesterol Metabolism
- ClinicalTrials.gov ID
- NCT02354079
- Acronym / sponsor ID
- HYPOCHOL / RC14_0400
- Conditions
- Hypobetalipoproteinemia
- Keywords
- Low LDL-C, Target Identification, Genetic, Endocrinology, Cardiovascular Disease
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 435 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 7 Jan 2016 (actual)
- Primary completion
- 7 Jan 2022 (actual)
- Study completion
- 7 Jan 2032 (estimated)
- First posted
- 3 Feb 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.
The aim of this study is to identify new targets in cholesterol metabolism thanks to a genetically-based strategy.
Detailed description
The goal is to recruit 400 subjects: 200 adult subjects with familial hypobetalipoproteinemia (FHBL) (index cases) plus 200 additional related subjects in at least 10 large informative FHBL families, in which there is no known mutation in FHBL genes.
The patient care is modified: patient will have an Hospital Anxiety and Depression (HAD) questionnaire (focus on depressive syndrome), a food diary, and some additional blood analysis (including genetic analysis).
One of the main issue to recruit FHBL patients is the fact that they are asymptomatic and that FHBL is not identified as a serious illness by their general physicians.
Step-1. Excluding mutations in selected candidate genes As a first approach to screen candidate genes and exclude patients with known mutations, the investigators developed a custom design based on the Haloplex™ technology (Agilent® Technologies) to perform high-throughput sequencing of the coding regions of 10 genes, including those previously described in FHBL (apolipoprotein B (APOB), Proprotein convertase subtilisin/kexin type 9 (PCSK9)), Microsomal triglyceride transfer protein (MTP or ABL), chylomicron retention disease (CMRD), Secretion associated, Ras related GTPase (SARA2 gene), as well as 6 additional candidate genes in cholesterol metabolism (low density lipoprotein receptor (LDLR), Sortilin (SORT1), Inducible Degrader of the LDL receptor (IDOL), Cholesteryl ester transfer protein (CETP), Apolipoprotein E (ApoE) and Angiopoietin-like Protein 3 (ANGTPL3)). All the recruited index cases (n=200) will be genotyped to select only those without mutations in previously described genes, being approximately 50% of our index case cohort.
Step-2. Identification of informative families and exome sequencing In patients without identified mutations, the investigators will conduct a familial screening in order to identify other cases of FHBL among proband relatives. An analysis of fasting plasma lipid parameters (total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Low-Density Lipoproteins (LDL-C) and triglycerides (TG)) will be performed for each related. Affected subjects will be determined by a spontaneous LDL-C < 80 mg/dl and/or apoB < 50 mg/dl. In contrast, non-affected subjects will display LDL-C > 80 mg/dl and/or apoB > 50 mg/dl.
For large families, the investigators will then combine whole-exome sequencing and linkage analysis to identify any novel genetic variant likely explaining FHBL. Depending on family pedigree, whole-exome sequencing (WES) will be performed on 2 to 5 patients per family. All relatives will be genotyped for linkage analysis.
In parallel to this genetic approach, a regional epidemiological analysis will be performed to identify some geographical clusters with a high prevalence of the disease, as developed in the project named VaCaRMe (for Vascular and Cardiac, Respiratory and Metabolic overcome diseases)
An additional aim, based on an exhaustive phenotyping of FHBL patients, is to investigate the safety of very low LDL-C and to perform some genotype-phenotype correlations in patients with FHBL population."
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| genetic analysis | Other | Genetic: hypobetalipoproteinemia genetic and genotypic screening |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- For index cases without family screening:
- o Patient with HBL: fasting LDL-C ≤ 50 mg/dl.
- For familial affected cases:
- All subjects, including familial non-affected cases, must give written consent (dated and signed) to participate at the constitution of biobank (including DNA samples and urine samples).
Key exclusion criteria (4 listed)
- Use of lipid-lowering drugs (statins, fibrates, ezetimibe, bile-acid sequestering resin) or nutraceuticals known to affect lipids (red yeast rice, margarine and dairy with plant sterol)
- Patient screened within an extreme metabolic disturbance (emergency situations, sepsis, hospitalization in intensive care unit)
- Patients with hyperthyroidism, severe liver failure, end stage chronic kidney disease, serious pancreatic failure, anemia related to thalassemia or sickle cell disease, strict vegan diet or malnutrition
- Refusal of the patient or his legal representative to participate in the study"
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hypobetalipoproteinemia genetic and genotypic screening | Genetic | genetic analysis |
Primary outcome
type and number of genetic abnormalities leading to FHBL
Time frame: ten years
To identify new gene involved in FHBL and determine genetic cause of FHBL (Patients with FHBL and their relatives will be recruited to establish familial forms of FHBL in large informative families with no mutations in known classical FHBL genes. This will allow perform genetic analysis using new approaches to genetic broadband (exome sequencing analysis + linkage analysis). This approach will allow specify which chromosomal regions are shared only by affected individuals, and identify new candidate genes).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
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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.
Charlotte AUTHIER, Doctor principal investigator
Health Care Centers of French Health Insurance in Saint-Nazaire
Didier GOXE principal investigator
Health Care Centers of French Health Insurance in La Roche sur Yon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hypobetalipoproteinemia genetic and genotypic screening in people with Hypobetalipoproteinemia, run by Nantes University Hospital 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 5 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 29 Apr 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
type and number of genetic abnormalities leading to FHBL (time frame: ten years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Apr 2026.