Clinical trial NCT06138509: Peripheral Serotonin and Albinism
Official title: Role of Peripheral Serotonin in Oculocutaneous Albinism
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Oculocutaneous Albinism
Keywords: Oculocutaneous albinism
Peripheral serotonin
Anemia
Microcytosis
Iron deficiency
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 160
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited during a dermatology consultation at the Necker-Enfants Malades hospital. Recruitment, diagnosis of albinism and clinical, dermatological and ophthalmological characterization, as well as biological tests, will be carried out by the MAGEC reference center in Necker hospital (reference center for rare diseases of the skin and mucous membranes of genetic origin).

Brief summary: Serotonin (5-HT or 5-hydroxytryptamine) is a monoamine primarily known for its role as a neurotransmitter in the central nervous system (CNS). However, the functions of serotonin go beyond its role in the central nervous system: different peripheral tissues have the capacity to produce and/or use serotonin locally, forming systems called "micro-serotonergic" systems. Among the peripheral roles of serotonin, previous work by the Iron and Immunity team, INSERM U1016, Institut Cochin (Paris), was able to show that serotonin has a positive role on erythropoiesis and the survival of red blood cells, and the team's ongoing work suggests that serotonin also impacts iron metabolism.

In humans and in mouse models, several studies have suggested a role for serotonin in pigmentation. In certain syndromic forms of albinism such as Hermansky Pudlak syndrome, platelet serotonin levels are reduced in connection with a decrease in dense platelet granules (delta granules): this characteristic is even part of the diagnostic criteria.

Preliminary data from the Iron and Immunity team found:

* Changes in serotonin levels in children with albinism compared to control patients,
* Changes in hemoglobin level and mean corpuscular volume (MCV) in children with albinism (towards anemia and microcytosis),
* Changes in the iron balance in children with albinism (towards iron deficiency).

The hypothesis of this research is that peripheral serotonin plays a role in the clinical and biological manifestations of oculocutaneous albinism.

Detailed description: Serotonin (5-HT or 5-hydroxytryptamine) is a monoamine primarily known for its role as a neurotransmitter in the central nervous system (CNS). However, the functions of serotonin go beyond its role in the central nervous system: different peripheral tissues have the capacity to produce and/or use serotonin locally, forming systems called "micro-serotonergic" systems. Among the peripheral roles of serotonin, previous work by the Iron and Immunity team, INSERM U1016, Institut Cochin (Paris), was able to show that serotonin has a positive role on erythropoiesis and the survival of red blood cells, and the team's ongoing work suggests that serotonin also impacts iron metabolism.

Albinism exhibits significant clinical and genetic heterogeneity with poor genotype-phenotype correlation, and nearly 15% of patients remain without a molecular diagnosis. There is no curative treatment for albinism. Patients with albinism suffer from physical disability throughout their lives, but can also suffer from psychological disability and discrimination. These patients are also more vulnerable to the effects of climate change. The unmet clinical needs are therefore enormous.

In humans and in mouse models, several studies have suggested an unexpected role for serotonin in skin pigmentation at several levels. Transcriptomic studies revealed that the Tph1 gene, responsible for serotonin synthesis outside the CNS, as well as serotonin receptors, were expressed in melanocytic and keratinocytic cell lines. Other studies have indicated that serotonin enhances melanogenesis in three melanocyte cell lines (B16F10, SK-MEL-2, Melan-a). Finally, studies suggest that serotonin is involved in pathologies such as certain congenital dyschromias, Rett syndrome and vitiligo. In certain syndromic forms of albinism such as Hermansky Pudlak syndrome, platelet serotonin levels are reduced in connection with a decrease in dense platelet granules (delta granules): this characteristic is even part of the diagnostic criteria.

Preliminary data from the Iron and Immunity team found:

* Changes in serotonin levels in children with albinism compared to control patients,
* Changes in hemoglobin level and mean corpuscular volume (MCV) in children with albinism (towards anemia and microcytosis),
* Changes in the iron balance in children with albinism (towards iron deficiency).

The hypothesis of this research is that peripheral serotonin plays a role in the clinical and biological manifestations of oculocutaneous albinism.

The study will assess serotonin and its metabolites in the serum of patients with albinism, and compare the results with controls patients. The level of serotonin and its metabolites will be correlated with the different genotypes, and with the severity of albinism within the same genotypes.

This study also wish to explore the impact of serotonin levels in the development of anemia, microcytosis and/or iron deficiency in patients with albinism. Complete blood counts and iron studies in patients with albinism will be compare to those of control patients too.

Eligibility criteria: Inclusion Criteria:

Patients:

* Patients with albinism aged 2 to 17 years
* Followed in the MAGEC-Necker reference center (reference center for rare diseases of the skin and mucous membranes of genetic origin), during the inclusion period
* Information of parental authority holders of patients and patients of understanding age, and collection of consent from parental authority holders and patients.

Controls:

* Patients aged 2 to 17 years old
* Having consulted in Necker hospital during the inclusion period in the emergency and surgical services and whose care required a blood test analyzed in the hematology laboratory of the Necker hospital.
* Normal complete blood count (CBC)
* Normal C-reactive protein test (CRP)
* Absence of opposition from parental authority holders within one month of after sending the study information note.

Exclusion Criteria:

Patients:

- Inability to have a blood test

Controls:

* Abnormal blood count
* Elevation of CRP above laboratory standard

Primary outcomes:
measure: Level of serotonin and its metabolites in serum
timeFrame: Day 0
Secondary outcomes:
measure: Correlation between serotonin levels and molecular subtype of albinism
timeFrame: Day 0
measure: Correlation between serotonin levels and severity of albinism
timeFrame: Day 0
measure: Correlation between serotonin levels and iron studies
timeFrame: Day 0
measure: Correlation between serotonin levels and hemoglobin
timeFrame: Day 0
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Smail HADJ-RABIA, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Sud Francilien (CHSF) and Cochin Institute, INSERM U1016, Team Iron and Immunity
name: Guillemette FOUQUET, MD
role: STUDY_DIRECTOR
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