Ignite Creation Date:
2024-05-06 @ 6:41 PM
Last Modification Date:
2024-10-26 @ 2:52 PM
Study NCT ID:
NCT05746845
Status:
RECRUITING
Last Update Posted:
2024-06-04
First Post:
2023-01-25
Brief Title:
Implication of 5-HT7 Receptor in Inflammatory Mechanisms in Multiple Sclerosis
Sponsor:
Centre Hospitalier Régional dOrléans
Organization:
Centre Hospitalier Régional dOrléans
Study Overview
Official Title:
RESEPTOR 5-HT7 Interest of the 5-HT7 Serotonin Receptor as a Biomarker in Multiple Sclerosis
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESEPTOR 5-HT7
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
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
Detailed Description:
In a previous translational study 5-HT SEP the expression modulation of 5-HT7 receptor in function of immunological context was investigated in different group of MS patients
Group 1 MS patients with an acute relapse
Group 2 MS stable patients treated with Natalizumab
Group 3 Healthy people from Etablissement Français du Sang From blood cells of different groups of individuals the investigators determined the percentage and intensity of expression of the receptor on circulating lymphocytes by flow cytometry
The investigators demonstrated in this first study that the 5-HT7 receptor is mainly expressed on the surface of B lymphocytes compared to T lymphocytes
Interestingly while the percentage of T lymphocytes CD4 CD8 remained unchanged between the 3 groups the investigators observed that the expression of R5-HT7 on the surface of the T lymphocyte subpopulations Th1 Th2 Th17 and Treg is significantly increased in the blood of MS patients treated with Natalizumab compared to healthy individuals and MS patients in relapse
Considering litterature data and our preliminary results showing the therapeutic potential of 5-HT7R ligand in animal models of MS as well as the upregulation of 5-HT7 expression in NTZ-treated patients 5-HTSEP study the investigators wish to go further with these investigations The main objective of this new translational study is to demonstrate the interest of the 5-HT7 serotonin receptor as a biomarker in the therapeutic monitoring of patients suffering from Multiple Sclerosis
The investigators first want to know if the increase in the expression of R5-HT7 on the surface of lymphocyte populations in stable MS patients is due specifically to Natalizumab treatment or if other treatments would also induce a similar effect To answer this question the investigators will study the expression of the receptor not only on the surface of lymphocyte cells but also on the surface of monocytes NK cells and polymorphonuclear cells cells not investigated in the first 5-HTSEP study in three groups of individuals
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 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
Group 1 healthy volunteers is a control group necessary for the smooth running of the study and the interpretation of the results
For group 2 the Natalizumab treatment has already been investigated during the previous 5-HTSEP study This new study will make it possible to 1 compare the expressionactivity of the receptor in the three groups 2 check the reproducibility of the results compared to the previous study 3 evaluate any variations linked to the temporality of the treatment with 2 blood samples a first before injection of Natalizumab a second 14 days later Indeed unlike the 5-HTSEP study where a single sample 1 month after injection of Natalizumab was analysed the investigators wish to take these two samples in order to carry out a longitudinal study making it possible to observe the evolution of the expression of the 5-HT7 receptor as a function of the temporality of the treatment
Group 3 will assess whether other treatments teriflunomide or fumarate can induce an effect similar to that observed after Natalizumab treatment which is associated with an increase of R5-HT7 expression on the surface of lymphocyte populations in stable MS patients
Group 1 MS patients with an acute relapse
Group 2 MS stable patients treated with Natalizumab
Group 3 Healthy people from Etablissement Français du Sang From blood cells of different groups of individuals the investigators determined the percentage and intensity of expression of the receptor on circulating lymphocytes by flow cytometry
The investigators demonstrated in this first study that the 5-HT7 receptor is mainly expressed on the surface of B lymphocytes compared to T lymphocytes
Interestingly while the percentage of T lymphocytes CD4 CD8 remained unchanged between the 3 groups the investigators observed that the expression of R5-HT7 on the surface of the T lymphocyte subpopulations Th1 Th2 Th17 and Treg is significantly increased in the blood of MS patients treated with Natalizumab compared to healthy individuals and MS patients in relapse
Considering litterature data and our preliminary results showing the therapeutic potential of 5-HT7R ligand in animal models of MS as well as the upregulation of 5-HT7 expression in NTZ-treated patients 5-HTSEP study the investigators wish to go further with these investigations The main objective of this new translational study is to demonstrate the interest of the 5-HT7 serotonin receptor as a biomarker in the therapeutic monitoring of patients suffering from Multiple Sclerosis
The investigators first want to know if the increase in the expression of R5-HT7 on the surface of lymphocyte populations in stable MS patients is due specifically to Natalizumab treatment or if other treatments would also induce a similar effect To answer this question the investigators will study the expression of the receptor not only on the surface of lymphocyte cells but also on the surface of monocytes NK cells and polymorphonuclear cells cells not investigated in the first 5-HTSEP study in three groups of individuals
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 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
Group 1 healthy volunteers is a control group necessary for the smooth running of the study and the interpretation of the results
For group 2 the Natalizumab treatment has already been investigated during the previous 5-HTSEP study This new study will make it possible to 1 compare the expressionactivity of the receptor in the three groups 2 check the reproducibility of the results compared to the previous study 3 evaluate any variations linked to the temporality of the treatment with 2 blood samples a first before injection of Natalizumab a second 14 days later Indeed unlike the 5-HTSEP study where a single sample 1 month after injection of Natalizumab was analysed the investigators wish to take these two samples in order to carry out a longitudinal study making it possible to observe the evolution of the expression of the 5-HT7 receptor as a function of the temporality of the treatment
Group 3 will assess whether other treatments teriflunomide or fumarate can induce an effect similar to that observed after Natalizumab treatment which is associated with an increase of R5-HT7 expression on the surface of lymphocyte populations in stable MS patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None