Peripheral Serotonin and Albinism (SEPIAs)

February 15, 2024 updated by: Assistance Publique - Hôpitaux de Paris

Role of Peripheral Serotonin in Oculocutaneous Albinism

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

160

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Paris, France, 75015
        • Recruiting
        • Hôpital Necker-Enfants Malades
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

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).

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients

Patients with albinism aged 2 to 17 years old and 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.

During an initial or a follow-up consultation for patients with albinism, an additional volume of blood will be drawn during a blood sample drawn as part of routine care.
Other: Dosage of serotonin and metabolites
The dosages of serotonin and its metabolites will be performed by the INSERM U1016 unit at Cochin Institute.
Other: Blood parameters
The characterization of blood parameters : complete blood count (CBC), reticulocytes, C-reactive protein (CRP), iron studies (ferritin, serum iron, transferrin and transferrin saturation), hemoglobin electrophoresis, erythropoietin, will be added using standard methods at the Necker hematology laboratory if not carried out as part of the routine care.
Control patients

Control patients are patients who were seen at Necker-Enfants Malades Hospital during the inclusion period, in the emergency and surgical departments, and whose care required a blood test analyzed in the Necker-Enfants Malades Hospital hematology laboratory.

These patients will be selected on their age (2 to 17 years old), and must have a normal complete blood count and CRP. Leftover blood not used by the hospital hematology laboratory will be used for study analyses.
Other: Dosage of serotonin and metabolites
The dosages of serotonin and its metabolites will be performed by the INSERM U1016 unit at Cochin Institute.
Other: Blood parameters
The characterization of blood parameters : complete blood count (CBC), reticulocytes, C-reactive protein (CRP), iron studies (ferritin, serum iron, transferrin and transferrin saturation), hemoglobin electrophoresis, erythropoietin, will be added using standard methods at the Necker hematology laboratory if not carried out as part of the routine care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of serotonin and its metabolites in serum
Time Frame: Day 0
Levels of serotonin and its metabolites in serum in children with albinism, compared with control children.
Day 0

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between serotonin levels and molecular subtype of albinism
Time Frame: Day 0
Sequencing allowing molecular characterization of albinism is an integral part of diagnosis.
Day 0
Correlation between serotonin levels and severity of albinism
Time Frame: Day 0
The severity of albinism : cutaneous severity is based on clinical estimation, and ophthalmological severity on visual acuity values and degree of foveal hypoplasia.
Day 0
Correlation between serotonin levels and iron studies
Time Frame: Day 0
Determination of ferritin, serum iron, transferrin and transferrin saturation.
Day 0
Correlation between serotonin levels and hemoglobin
Time Frame: Day 0
Results of complete blood count, reticulocytes, hemoglobin electrophoresis in case of microcytosis, and erythropoietin dosage.
Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Smail HADJ-RABIA, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Study Director: Guillemette FOUQUET, MD, Centre Hospitalier Sud Francilien (CHSF) and Cochin Institute, INSERM U1016, Team Iron and Immunity

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 6, 2024

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

November 14, 2023

First Submitted That Met QC Criteria

November 14, 2023

First Posted (Actual)

November 18, 2023

Study Record Updates

Last Update Posted (Actual)

February 16, 2024

Last Update Submitted That Met QC Criteria

February 15, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP230808
  • 2023-A01431-44 (Other Identifier: IDRCB Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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