Peripheral Serotonin and Albinism

NCT06138509 | Recruiting

• 2 other identifiers: APHP2308082023-A01431-44
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

Oculocutaneous Albinism

Keywords

Oculocutaneous albinism; Peripheral serotonin; Anemia; Microcytosis; Iron deficiency

Outcome Measures

Primary Outcomes (1)

• Level of serotonin and its metabolites in serum

  Levels of serotonin and its metabolites in serum in children with albinism, compared with control children.

  Day 0

Secondary Outcomes (4)

• Correlation between serotonin levels and molecular subtype of albinism

  Day 0

• Correlation between serotonin levels and severity of albinism

  Day 0

• Correlation between serotonin levels and iron studies

  Day 0

• Correlation between serotonin levels and hemoglobin

  Day 0

Study Arms (2)

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; Other: Blood parameters

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; Other: Blood parameters

Interventions

Dosage of serotonin and metabolites OTHER

The dosages of serotonin and its metabolites will be performed by the INSERM U1016 unit at Cochin Institute.

Control patients; Patients

Blood parameters OTHER

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; Patients

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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).

You may qualify if:

• Patients:
• Patients with albinism aged 2 to 17 years
• 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
• 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.

You may not qualify if:

• Patients:
• \- Inability to have a blood test
• Controls:
• Abnormal blood count
• Elevation of CRP above laboratory standard

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hôpital Necker-Enfants Malades

Paris, 75015, France

RECRUITING

Related Publications (15)

• Amireault P, Sibon D, Cote F. Life without peripheral serotonin: insights from tryptophan hydroxylase 1 knockout mice reveal the existence of paracrine/autocrine serotonergic networks. ACS Chem Neurosci. 2013 Jan 16;4(1):64-71. doi: 10.1021/cn300154j. Epub 2012 Nov 7.

  PMID: 23336045 BACKGROUND

• Yabut JM, Crane JD, Green AE, Keating DJ, Khan WI, Steinberg GR. Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule. Endocr Rev. 2019 Aug 1;40(4):1092-1107. doi: 10.1210/er.2018-00283.

  PMID: 30901029 BACKGROUND

• Fouquet G, Coman T, Hermine O, Cote F. Serotonin, hematopoiesis and stem cells. Pharmacol Res. 2019 Feb;140:67-74. doi: 10.1016/j.phrs.2018.08.005. Epub 2018 Aug 11.

  PMID: 30107202 BACKGROUND

• English KB, Wang ZZ, Stayner N, Stensaas LJ, Martin H, Tuckett RP. Serotonin-like immunoreactivity in Merkel cells and their afferent neurons in touch domes from the hairy skin of rats. Anat Rec. 1992 Jan;232(1):112-20. doi: 10.1002/ar.1092320112.

  PMID: 1536455 BACKGROUND

• Johansson O, Liu PY, Bondesson L, Nordlind K, Olsson MJ, Lontz W, Verhofstad A, Liang Y, Gangi S. A serotonin-like immunoreactivity is present in human cutaneous melanocytes. J Invest Dermatol. 1998 Dec;111(6):1010-4. doi: 10.1046/j.1523-1747.1998.00460.x.

  PMID: 9856809 BACKGROUND

• Lee HJ, Park MK, Kim SY, Park Choo HY, Lee AY, Lee CH. Serotonin induces melanogenesis via serotonin receptor 2A. Br J Dermatol. 2011 Dec;165(6):1344-8. doi: 10.1111/j.1365-2133.2011.10490.x. Epub 2011 Oct 17.

  PMID: 21711335 BACKGROUND

• Slominski A, Pisarchik A, Semak I, Sweatman T, Wortsman J, Szczesniewski A, Slugocki G, McNulty J, Kauser S, Tobin DJ, Jing C, Johansson O. Serotoninergic and melatoninergic systems are fully expressed in human skin. FASEB J. 2002 Jun;16(8):896-8. doi: 10.1096/fj.01-0952fje. Epub 2002 Apr 23.

  PMID: 12039872 BACKGROUND

• Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J. Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol. 2003 Jul;196(1):144-53. doi: 10.1002/jcp.10287.

  PMID: 12767050 BACKGROUND

• Zhou L, Cai M, Ren Y, Wu H, Liu M, Chen H, Shang J. The different roles of 5-HT1A/2A receptors in fluoxetine ameliorated pigmentation of C57BL/6 mouse skin in response to stress. J Dermatol Sci. 2018 Dec;92(3):222-229. doi: 10.1016/j.jdermsci.2018.10.002. Epub 2018 Oct 25.

  PMID: 30527375 BACKGROUND

• Liu L, Fu M, Pei S, Zhou L, Shang J. R-Fluoxetine Increases Melanin Synthesis Through a 5-HT1A/2A Receptor and p38 MAPK Signaling Pathways. Int J Mol Sci. 2018 Dec 25;20(1):80. doi: 10.3390/ijms20010080.

  PMID: 30585252 BACKGROUND

• Enkhtaivan E, Lee CH. Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication. Int J Mol Sci. 2021 Jul 28;22(15):8071. doi: 10.3390/ijms22158071.

  PMID: 34360837 BACKGROUND

• Schallreuter KU, Salem MA, Gibbons NC, Martinez A, Slominski R, Ludemann J, Rokos H. Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: Epidermal H2O2/ONOO(-)-mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low serotonin and melatonin levels. FASEB J. 2012 Jun;26(6):2457-70. doi: 10.1096/fj.11-197137. Epub 2012 Mar 13.

  PMID: 22415302 BACKGROUND

• Maurer-Spurej E, Dyker K, Gahl WA, Devine DV. A novel immunocytochemical assay for the detection of serotonin in platelets. Br J Haematol. 2002 Mar;116(3):604-11. doi: 10.1046/j.0007-1048.2001.03302.x.

  PMID: 11849219 BACKGROUND

• Thompson JH. Iron absorption and serotonin (5-hydroxytryptamine) antagonism. Arch Int Pharmacodyn Ther. 1965 Aug;156(2):249-54. No abstract available.

  PMID: 5868935 BACKGROUND

• Amireault P, Hatia S, Bayard E, Bernex F, Collet C, Callebert J, Launay JM, Hermine O, Schneider E, Mallet J, Dy M, Cote F. Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice. Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13141-6. doi: 10.1073/pnas.1103964108. Epub 2011 Jul 25.

  PMID: 21788492 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood serum

MeSH Terms

Conditions

Albinism, Oculocutaneous; Anemia; Iron Deficiencies

Condition Hierarchy (Ancestors)

Albinism; Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders

Study Officials

• Smail HADJ-RABIA, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Guillemette FOUQUET, MD

  Centre Hospitalier Sud Francilien (CHSF) and Cochin Institute, INSERM U1016, Team Iron and Immunity

  STUDY DIRECTOR

Central Study Contacts

Smail HADJ-RABIA, MD, PhD

CONTACT

1 44 49 46 62; smail.hadjrabia@aphp.fr

Hélène Morel

CONTACT

1 44 38 16 53; helene.morel@aphp.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 18, 2023
• Study Start: February 6, 2024
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)