Implication of 5-HT7 Receptor in Inflammatory Mechanisms in Multiple Sclerosis

NCT05746845 | Completed

• 1 other identifier: CHRO-2021-07
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple Sclerosis is a chronic autoimmune disease associated with inflammatory response harmful for the Central Nervous System. Immunological imbalance is involved with Th1 and Th17 cells in correlation with a disturbance of regulators mechanisms as Treg cells. Despite years of research, the mechanisms involved remain unclear. Serotonin (5-HT) seems to be play an essential role in developing CNS inflammatory diseases and in particular in MS. Indeed, several studies have shown the anti-inflammatory potential of this neurotransmitter and also its vulnerability in inflammatory context. Moreover, a recent study has shown that 5-HT can reduced CD4 T cells proliferation and pro-inflammatory cytokines released in vitro. Interestingly, treatment, treatment with SSRIs (selective serotonin reuptake inhibitor) in an animal model of MS, on Experimental Autoimmune Encephalomyelitis, was shown to improve the clinical score and promote remission of the disease. Among serotonin receptors, the 5-HT7 receptor, can be considered as an interesting target to treat neurological disorders associated with inflammatory context. Present in humans and mice, this receptor is expressed on the surface of a large number of cells, such as T-lymphocytes, macrophages, dendritic cells as well as on cells of CNS such as neurons, astrocytes and microglia. Given the importance of the positive cells for 5-HT7 receptor, in the inflammatory context observed in multiple sclerosis, the investigators propose to study the receptor expression in blood samples from multiple sclerosis patient.

Conditions

Healthy; Multiple Sclerosis

Keywords

Multiple sclerosis; Serotonin; 5-HT7 receptor; Inflammation; Lymphocytes; Monocytes; Cytokines

Outcome Measures

Primary Outcomes (1)

• 5-HT7 receptor expression on circulating cells

  using the flow cytometry technique, on whole blood, we will perform immunophenotyping in order to determine the fluorescence intensity of cells positive for the receptor (5-HT7+ cells) (B, T and NK lymphocytes, monocytes, and polynuclear cells) in the different groups of individuals.

  Day 1

Secondary Outcomes (5)

• Expression of the 5-HT7 receptor after positive selection of different cell populations from PBMC

  Day 15

• Expression of the different isoforms of the 5-HT7 receptor on PBMC

  Day 15

• Functional activity of the 5-HT7 receptor on PBMC: protein studies

  Day 15

• Functional activity of the 5-HT7 receptor on PBMC: mRNA expression studies

  Day 15

• Relationship between Multiple sclerosis treatment on inflammation and serotonin production in serum

  Day 15

Study Arms (3)

Healthy individuals

Group 1: Healthy individuals, so-called "control" donors whose blood samples will be collected from the EFS (French Blood Establishment)

Biological: Blood sample

Stable MS patients treated with high efficacy treatment

Group 2: Stable MS patients without inflammatory activity of the disease treated with high efficacy treatment (Natalizumab or Ocrelizumab)

Biological: Blood sample

Stable MS patients treated with moderately effective treatment

Group 3: Stable MS patients without inflammatory disease activity treated with moderately effective treatment (Teriflunomide or Fumarate)

Biological: Blood sample

Interventions

Blood sample BIOLOGICAL

Blood sampling will be done on three groups: Group 1: Healthy volunteers, so-called "control" donors whose blood samples will be ordered from the EFS (French Blood Establishment) Group 2: Stable MS patients without inflammatory activity of the disease treated with high efficacy treatment (Natalizumab or Ocrelizumab) Group 3: Stable MS patients without inflammatory disease activity treated with moderately effective treatment (Teriflunomide or Fumarate)

Healthy individuals; Stable MS patients treated with high efficacy treatment; Stable MS patients treated with moderately effective treatment

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Group 1: Healthy individuals, so-called "control" donors whose blood samples will be collected from the EFS (French Blood Establishment) Group 2: Stable MS patients without inflammatory activity of the disease under high efficacy treatment (Natalizumab or Ocrelizumab) Group 3: Stable MS patients without inflammatory disease activity under moderately effective treatment (Teriflunomide or Fumarate)

You may qualify if:

• Men and women
• Aged between 18 and 50 years old,
• With multiple sclerosis already diagnosed and fulfilling the modified Mc Donald criteria
• Stable (no relapse in the last 6 months and MRI less than a year old, with no new lesions) and with at least 1 year of treatment with Natalizumab, Ocrelizumab, Teriflunomide or Fumarate
• Subject medically fit to give a maximum of 50 ml of extra whole blood
• Patient having given their consent to participate in the study

You may not qualify if:

• HIV serology known or discovered during the present episode
• Demented patient
• Patient treated with corticosteroids in the last month
• Non-affiliated person or non-beneficiary of a social security scheme
• Uncooperative patient
• Patient under legal protection, guardianship or curatorship
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Centre Hospitalier Régional d'Orléans: lead

Study Sites (1)

CHU Orléans

Orléans, 45067, France

Location

Related Publications (2)

• Sacramento PM, Monteiro C, Dias ASO, Kasahara TM, Ferreira TB, Hygino J, Wing AC, Andrade RM, Rueda F, Sales MC, Vasconcelos CC, Bento CAM. Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4+ T-cell subsets in multiple sclerosis patients. Eur J Immunol. 2018 Aug;48(8):1376-1388. doi: 10.1002/eji.201847525. Epub 2018 Jun 6.

  PMID: 29719048 RESULT

• Yuan XQ, Qiu G, Liu XJ, Liu S, Wu Y, Wang X, Lu T. Fluoxetine promotes remission in acute experimental autoimmune encephalomyelitis in rats. Neuroimmunomodulation. 2012;19(4):201-8. doi: 10.1159/000334095. Epub 2012 Mar 21.

  PMID: 22441536 RESULT

MeSH Terms

Conditions

Multiple Sclerosis; Inflammation

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Maud PALLIX-GUYOT, Dr

  CHU Orleans

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: February 28, 2023
• Study Start: March 6, 2023
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

FR (1)