Clinical trial NCT05208879: CArotenoid in hypoChOlesterolemia
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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Intestinal Hypocholesterolemia
Abetalipoproteinemia
Chylomicron Retention Disease
Keywords: Abetalipoproteinemia,
Chylomicron Retention Disease
Hypocholesterolemia
Macula Pigment
Retinitis Pigmentosa
Carotenoids
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2022-01-26
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: The principal outcome measure is the macular pigment optical density (OD)
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Bron
country: France
facility: UF nutrition pédiatrique, Service hépatologie, gastroentérologie et nutrition pédiatrique Hôpital Femme Mère Enfant de Lyon (GHE-HFME)
city: Bron
country: France
facility: Fédération d'endocrinologie, maladies métaboliques, diabète et nutrition Hôpital cardiovasculaire et pneumologique Louis Pradel
city: Bron
country: France
facility: UF nutrition pédiatrique, Service hépatologie, gastroentérologie et nutrition pédiatrique Hôpital Femme Mère Enfant de Lyon (GHE-HFME)
Study officials:
affiliation: Hospices Civils de Lyon
name: Peretti Noël, Pr
role: PRINCIPAL_INVESTIGATOR
References: