Primary Intestinal HypocholesterolemiaCaCoNCT05208879
CArotenoid in hypoChOlesterolemia
An observational study of Primary Intestinal Hypocholesterolemia and Abetalipoproteinemia, run by Hospices Civils de Lyon at 3 sites in France.
Trial summary
Hypobetalipoproteinemias (HBL) represent a heterogeneous group of disorders characterized by reduced plasma levels of plasmatic lipids (mainly triglycerides, total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B (apoB)) below the 5th percentile of the general population adjusted for age, gender. Read more about this study
- Who is it for?
- Ages 6 to 50 years
- Conditions the study is for
- Primary Intestinal Hypocholesterolemia, Abetalipoproteinemia, Chylomicron Retention Disease
- What is being tested?
- Characterization of carotenoid status and plasma levels of oxidative stress markers in patients (case group only) and Characterization, evaluation and comparison of macular pigment density
- How many people
- 10 participants
- Where
- 3 sitesFrance
- Study dates
- 30 Jun 2022to 7 Nov 2024
- 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 6 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: This study relates to adults or children over 6 years of age (cooperation necessary to perform the fundus) with primary intestinal hypocholesterolemia. The control population comprising major control patients under the age of 50 (limit the risk of age-related macular degeneration - AMD) or under age over 6 (cooperation necessary to perform OF) routinely monitored in the service of ophthalmology requiring a fundus examination as part of their usual follow-up.
Who may be able to join
- Genetically proven family hypocholesterolemia patients,
- Patients systematically monitored in the Gastroenterology and Paediatric Nutrition department of the Women's Hospital Mother Child of Lyon or in the adult endocrinology department of the GHE (Louis Pradel Hospital),
- Girl/woman or boy/man over 6 years and over 12 kg at the time of inclusion (age required for cooperation on macular pigment measurement),
- No objection from the patient or their parents/legal tutors in the case of a minor patient,
- Patient covered by social security.
Who cannot join
- Allergy to local anesthetics (especially xylocaine)
- Mydriatic allergy
- Person participating in another research with an exclusion period still in progress at pre-inclusion
- Person subject to a safeguard measure.
Trial locations and contacts
3 sites in 1 country.
France3 sites
Fédération d'endocrinologie, maladies métaboliques, diabète et nutrition Hôpital cardiovasculaire et pneumologique Louis Pradel
Bron, Bron, 69677
UF nutrition pédiatrique, Service hépatologie, gastroentérologie et nutrition pédiatrique Hôpital Femme Mère Enfant de Lyon (GHE-HFME)
Bron, Bron, 69677
UF nutrition pédiatrique, Service hépatologie, gastroentérologie et nutrition pédiatrique Hôpital Femme Mère Enfant de Lyon (GHE-HFME)
Bron, 69500
About this study
Official title: Characterization of the Density of Macular Pigment in Patients With Primary Intestinal Hypocholesterolemia and Its Relation to Their Carotenoid and Anti-oxidant Status.
Hypobetalipoproteinemias (HBL) represent a heterogeneous group of disorders characterized by reduced plasma levels of plasmatic lipids (mainly triglycerides, total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B (apoB)) below the 5th percentile of the general population adjusted for age, gender. HBL may be attributed to inherited disorders caused by mutations in several known genes. Intestinal recessive HBL includes abetalipoproteinemia (ABL) (OMIM 200100) and Chylomicron Retention Disease (CMRD) (OMIM 246700) - also called Anderson's disease. Those two recessives form of HBL are the ones considered in this study. ABL is due to mutations in the Microsomal Triglyceride Transfer Protein (MTTP) gene which is required for the assembly and secretion of apoB-containing lipoproteins: Low-Density Lipoprotein (LDL) and chylomicrons (CM) in both liver and intestine. Similarly, CMRD is due to mutations in the Sar1b gene encoding the Sar1b protein involved in the control of the intracellular trafficking of CMs in COPII-coated vesicles. Due to a defect in Apolipoprotein B-containing lipoproteins these diseases are characterized by dietary lipids and fat-soluble vitamins (A, D, E, K) malabsorption inducing digestive and growth disorders from birth. In parallel, neurological manifestations may appear, mainly as a consequence of vitamin E and A deficiencies.
Ophthalmological disorders are inconstant, with many patients being asymptomatic until adulthood. Loss of night or color vision are the first symptoms associated with retinal degeneration. Without treatment with high doses of vitamins, retinal degeneration can lead to blindness. The exact biological mechanism still remains unknown. Indeed, cases described in the scientific literature demonstrate that early treatment with high doses of vitamin E and A can stop or prevent neurological complications in the vast majority of patients; however, ophthalmic complications have a more versatile response.
Read more
Thus, despite early vitamin supplementation, several cases of adolescent or adult patients with vision impairment in the form of retinitis pigmentosa have been reported. This so-called secondary retinitis pigmentosa is characterized by a progressive loss of photoreceptors and a dysfunction of the pigmentary epithelium resulting in a progressive and gradual loss of vision, usually leading to blindness. Interestingly, primary (i.e., genetic) retinitis pigmentosa are characterized by "macula lutea" atrophy composed of two lipophilic molecules from the carotenoid xanthophyll family lutein and zeaxanthin, also known as macular pigments. Moreover, preliminary data seem to show that the patients considered for this study, present decreased plasmatic carotene concentrations as well as plasmatic vitamin E concentrations largely lower than the threshold of normality.
Thus, even if early treatment seems to prevent major ophthalmic complications, it does not provide total ophthalmic protection, which suggests the involvement of other factors among which carotenoids could occupy a prominent place given their essential role in maintaining the integrity of the macula.
- Conditions
- Primary Intestinal Hypocholesterolemia, Abetalipoproteinemia, Chylomicron Retention Disease
- Being tested
- Characterization of carotenoid status and plasma levels of oxidative stress markers in patients (case group only), Characterization, evaluation and comparison of macular pigment density
- Keywords
- Abetalipoproteinemia,, Chylomicron Retention Disease, Hypocholesterolemia, Macula Pigment, Retinitis Pigmentosa, Carotenoids
- Medical subject headings
- Abetalipoproteinemia, Chylomicron retention disease, Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Characterization of carotenoid status and plasma levels of oxidative stress markers in patients (case group only)Biological
Carotenoid status will be determined by measuring plasma and erythrocyte concentrations of lutein and zeaxanthin obtained during an annual blood draw. These molecules will be analyzed by high performance liquid chromatography.
The oxidative stress markers will be measured, in the blood sample already collected, thanks to specific assay kits: Erythrocyte reduced glutathione, Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Plasma and erythrocyte malondialdehyde, Plasma vitamin C, Plasma oxidized cholesterol, F2-isoprostanes.
This study does not result in any change in patient management, but requires the collection of an additional volume of blood (14 ml of study-specific blood) during the annual blood draw performed as part of routine patient follow-up.
Characterization, evaluation and comparison of macular pigment densityOther
The macular pigment optical density (OD) will be determined by an additional photograph during the fundus usually performed for annual follow-up through two-wavelength autofluorescence imaging. Indeed, the measurement of the optical density consists of an additional post-examination analysis of additional retinal images obtained during the fundus performed for the patients' ophthalmologic follow-up.
| Study group | Role | What they receive |
|---|---|---|
| Case group. | Patients with genetically proven familial hypocholesterolemia, who will accept to participate in this study and have been treated for this pathology since 1990 in the Department of Gastroenterology and Paediatric Nutrition (Pr Peretti) and continue their follow-up into adulthood at the GHE (Groupement Hospitalier Est) in Lyon in the endocrinology-nutrition service (Pr Moulin).
They may be girl/woman or boy/man over 6 years of age and over 12 kg at the time of inclusion (age required for cooperation on macular pigment measurement), agreeing to participate in the study with clear and informed consent. These patients are covered by social security. Receives: Biological: Characterization of carotenoid status and plasma levels of oxidative stress markers in patients (case group only) | |
| Control group. | The control group consists of children over 6 years old or adult patients, followed routinely in the ophthalmology department of the Edouard Herriot Hospital, Lyon (Pr Kodjikian) not suffering from genetic hypocholesterolemia and requiring a fundus examination as part of the usual follow-up of their ocular pathology, if this pathology does not interfere with the macular pigment density. An additional measurement of the macular pigment density will be made during this examination. The control group is only needed for the macular pigment analysis. No control group is considered for the characterization of plasma lutein and zeaxanthin deficiency and for the analysis of oxidative stress, so there will be no additional blood sampling for control patients. Receives: Other: Characterization, evaluation and comparison of macular pigment density |
What is being measured
The primary outcome is the main question the study is designed to answer.
The principal outcome measure is the macular pigment optical density (OD)
The macular pigment optical density (OD) will be determined by an additional photograph during the fundus usually performed for annual follow-up through two-wavelength autofluorescence imaging. This imaging method provides a profile of autofluorescence distribution calculated using a gray intensity scale in the center of the macula and along the horizontal and vertical meridians. The optical density of the macular pigment is then expressed as the logarithm of the ratio of the peri-oval/foveal excitation spectra symbolized by the acronym "DU" ("Density Unit"). Indeed, in autofluorescence, the lipofuscin chromophores are generally excited with two wavelengths: a first one which is located in the blue spectral region where the absorption band of the lipofuscin overlaps that of the macular pigments, and a second one which is always located in the absorption region of the lipofuscin but outside the absorption range of the macular pigments. Thus, excitation by the first (green) light causes
Measured: The optical density measurement will be performed, in addition to the usual patient follow-up tests, during a single visit to the ophthalmology department on a date chosen by the patient.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start30 Jun 2022
- Primary completion7 Nov 2024
- Study completion7 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Intestinal HypocholesterolemiaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peretti Noël, Pr, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05208879
- Sponsor's protocol ID
- 69HCL21_0720
- Acronym
- CaCo
- Status last verified
- Nov 2025
- First submitted
- 12 Jan 2022
- Last updated
- 4 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of the Density of Macular Pigment in Patients With Primary Intestinal Hypocholesterolemia and Its Relation to Their Carotenoid and Anti-oxidant Status.
- ClinicalTrials.gov ID
- NCT05208879
- Acronym / sponsor ID
- CaCo / 69HCL21_0720
- Conditions
- Primary Intestinal Hypocholesterolemia, Abetalipoproteinemia, Chylomicron Retention Disease
- Keywords
- Abetalipoproteinemia,, Chylomicron Retention Disease, Hypocholesterolemia, Macula Pigment, Retinitis Pigmentosa, Carotenoids
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 30 Jun 2022 (actual)
- Primary completion
- 7 Nov 2024 (actual)
- Study completion
- 7 Nov 2024 (actual)
- First posted
- 26 Jan 2022 (actual)
- 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.
Hypobetalipoproteinemias (HBL) represent a heterogeneous group of disorders characterized by reduced plasma levels of plasmatic lipids (mainly triglycerides, total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B (apoB)) below the 5th percentile of the general population adjusted for age, gender. HBL may be attributed to inherited disorders caused by mutations in several known genes. Intestinal recessive HBL includes abetalipoproteinemia (ABL) (OMIM 200100) and Chylomicron Retention Disease (CMRD) (OMIM 246700) - also called Anderson's disease. Those two recessives form of HBL are the ones considered in this study. ABL is due to mutations in the Microsomal Triglyceride Transfer Protein (MTTP) gene which is required for the assembly and secretion of apoB-containing lipoproteins: Low-Density Lipoprotein (LDL) and chylomicrons (CM) in both liver and intestine. Similarly, CMRD is due to mutations in the Sar1b gene encoding the Sar1b protein involved in the control of the intracellular trafficking of CMs in COPII-coated vesicles. Due to a defect in Apolipoprotein B-containing lipoproteins these diseases are characterized by dietary lipids and fat-soluble vitamins (A, D, E, K) malabsorption inducing digestive and growth disorders from birth. In parallel, neurological manifestations may appear, mainly as a consequence of vitamin E and A deficiencies.
Ophthalmological disorders are inconstant, with many patients being asymptomatic until adulthood. Loss of night or color vision are the first symptoms associated with retinal degeneration. Without treatment with high doses of vitamins, retinal degeneration can lead to blindness. The exact biological mechanism still remains unknown. Indeed, cases described in the scientific literature demonstrate that early treatment with high doses of vitamin E and A can stop or prevent neurological complications in the vast majority of patients; however, ophthalmic complications have a more versatile response.
Thus, despite early vitamin supplementation, several cases of adolescent or adult patients with vision impairment in the form of retinitis pigmentosa have been reported. This so-called secondary retinitis pigmentosa is characterized by a progressive loss of photoreceptors and a dysfunction of the pigmentary epithelium resulting in a progressive and gradual loss of vision, usually leading to blindness. Interestingly, primary (i.e., genetic) retinitis pigmentosa are characterized by "macula lutea" atrophy composed of two lipophilic molecules from the carotenoid xanthophyll family lutein and zeaxanthin, also known as macular pigments. Moreover, preliminary data seem to show that the patients considered for this study, present decreased plasmatic carotene concentrations as well as plasmatic vitamin E concentrations largely lower than the threshold of normality.
Thus, even if early treatment seems to prevent major ophthalmic complications, it does not provide total ophthalmic protection, which suggests the involvement of other factors among which carotenoids could occupy a prominent place given their essential role in maintaining the integrity of the macula.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case group. | – | Biological: Characterization of carotenoid status and plasma levels of oxidative stress markers in patients (case group only)Patients with genetically proven familial hypocholesterolemia, who will accept to participate in this study and have been treated for this pathology since 1990 in the Department of Gastroenterology and Paediatric Nutrition (Pr Peretti) and continue their follow-up into adulthood at the GHE (Groupement Hospitalier Est) in Lyon in the endocrinology-nutrition service (Pr Moulin). They may be girl/woman or boy/man over 6 years of age and over 12 kg at the time of inclusion (age required for cooperation on macular pigment measurement), agreeing to participate in the study with clear and informed consent. These patients are covered by social security. |
| Control group. | – | Other: Characterization, evaluation and comparison of macular pigment densityThe control group consists of children over 6 years old or adult patients, followed routinely in the ophthalmology department of the Edouard Herriot Hospital, Lyon (Pr Kodjikian) not suffering from genetic hypocholesterolemia and requiring a fundus examination as part of the usual follow-up of their ocular pathology, if this pathology does not interfere with the macular pigment density. An additional measurement of the macular pigment density will be made during this examination. The control group is only needed for the macular pigment analysis. No control group is considered for the characterization of plasma lutein and zeaxanthin deficiency and for the analysis of oxidative stress, so there will be no additional blood sampling for control patients. |
Who may qualify
- Ages
- 6 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- This study relates to adults or children over 6 years of age (cooperation necessary to perform the fundus) with primary intestinal hypocholesterolemia. The control population comprising major control patients under the age of 50 (limit the risk of age-related macular degeneration - AMD) or under age over 6 (cooperation necessary to perform OF) routinely monitored in the service of ophthalmology requiring a fundus examination as part of their usual follow-up.
Key inclusion criteria (5 listed)
- Genetically proven family hypocholesterolemia patients,
- Patients systematically monitored in the Gastroenterology and Paediatric Nutrition department of the Women's Hospital Mother Child of Lyon or in the adult endocrinology department of the GHE (Louis Pradel Hospital),
- Girl/woman or boy/man over 6 years and over 12 kg at the time of inclusion (age required for cooperation on macular pigment measurement),
- No objection from the patient or their parents/legal tutors in the case of a minor patient,
- Patient covered by social security.
Key exclusion criteria (4 listed)
- Allergy to local anesthetics (especially xylocaine)
- Mydriatic allergy
- Person participating in another research with an exclusion period still in progress at pre-inclusion
- Person subject to a safeguard measure.
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 |
|---|---|---|
| Characterization of carotenoid status and plasma levels of oxidative stress markers in patients (case group only)Carotenoid status will be determined by measuring plasma and erythrocyte concentrations of lutein and zeaxanthin obtained during an annual blood draw. These molecules will be analyzed by high performance liquid chromatography. The oxidative stress markers will be measured, in the blood sample already collected, thanks to specific assay kits: Erythrocyte reduced glutathione, Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Plasma and erythrocyte malondialdehyde, Plasma vitamin C, Plasma oxidized cholesterol, F2-isoprostanes. This study does not result in any change in patient management, but requires the collection of an additional volume of blood (14 ml of study-specific blood) during the annual blood draw performed as part of routine patient follow-up. | Biological | Case group. |
| Characterization, evaluation and comparison of macular pigment densityThe macular pigment optical density (OD) will be determined by an additional photograph during the fundus usually performed for annual follow-up through two-wavelength autofluorescence imaging. Indeed, the measurement of the optical density consists of an additional post-examination analysis of additional retinal images obtained during the fundus performed for the patients' ophthalmologic follow-up. | Other | Control group. |
Primary outcome
The principal outcome measure is the macular pigment optical density (OD)
Time frame: The optical density measurement will be performed, in addition to the usual patient follow-up tests, during a single visit to the ophthalmology department on a date chosen by the patient.
The macular pigment optical density (OD) will be determined by an additional photograph during the fundus usually performed for annual follow-up through two-wavelength autofluorescence imaging. This imaging method provides a profile of autofluorescence distribution calculated using a gray intensity scale in the center of the macula and along the horizontal and vertical meridians. The optical density of the macular pigment is then expressed as the logarithm of the ratio of the peri-oval/foveal excitation spectra symbolized by the acronym "DU" ("Density Unit"). Indeed, in autofluorescence, the lipofuscin chromophores are generally excited with two wavelengths: a first one which is located in the blue spectral region where the absorption band of the lipofuscin overlaps that of the macular pigments, and a second one which is always located in the absorption region of the lipofuscin but outside the absorption range of the macular pigments. Thus, excitation by the first (green) light causes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2025.
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.
Peretti Noël, Pr principal investigator
Hospices Civils de Lyon
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Intestinal Hypocholesterolemia and Abetalipoproteinemia, run by Hospices Civils de Lyon at 3 sites 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: finished, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
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?
The principal outcome measure is the macular pigment optical density (OD) (time frame: The optical density measurement will be performed, in addition to the usual patient follow-up tests, during a single visit to the ophthalmology department on a date chosen by the patient.). 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 4 Dec 2025.