Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06549270
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-08
Brief Title:
Biochemical Profiling of Migraine Patients
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Unraveling the Spectrum of Migraine Resistant to Treatments Searching for Novel Biological PHEnotypes and theRApeutic Approaches SPHERA Project
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SPHERA_WP1_1
Brief Summary:
Aim of the study was to assess a potential dysfunction of the endocannabidiome system eCBome in migraine patients Migraine patients who will undergo preventive therapy with monoclonal antibodies directed against the calcitonin gene related peptide mAbs will be evaluated through a deep phenotyping of peripheral neurochemical biomarkers eCBome neuropeptides cytokines and kynurenine levels and microRNAs expression
Primary aim is to assess baseline differences among those patients who achieved a reduction of monthly migraine days 50 after three months of tretament namely Responders and those who did not namely Non-responders
Primary aim is to assess baseline differences among those patients who achieved a reduction of monthly migraine days 50 after three months of tretament namely Responders and those who did not namely Non-responders
Detailed Description:
Previous evidence showed that endocannabidiome system eCBome is altered in migraine patients demonstrating i altered gene expression of catabolizing enzymes MAGL and FAAH in patients with episodic and chronic migraine compared to healthy controls ii altered peripheral levels of the endocannabinoid-like lipid palmitoylethanolamide PEA with evidence of increased PEA levels during the acute migraine phase
Despite the high effectiveness and tolerability of mAbs monoclonal antibodies directed against the Calcitonin gene related peptide mAbs evidence from RCTs and real-life studies demonstrates that mAbs fail in 40 of patients These patients may bear a non CGRP- dependent phenotype potentially linked to eCBome dysfunction
Primary aim is to perform a deep phenotyping of the whole cohort of migraine patients comparing the subgroups of those patients who will be Responders to mAbs treatment namely those patients who achieved a reduction of monthly migraine days 50 compared to the Non-Respoder group namely those patients who achieved a reduction of monthly migraine days 50
Neuropeptides microRNAs inflammatory cytokines and kynurenine metabolites will be evaluated These findings will allow the identification of a multibiomarkers panel signature of migraine patients resisting to specifically targeted preventive treatments and potentially unveiling other molecular targets
STUDY DESIGN
This study is part of the SPHERA project with funding from the Italian Ministry of Health GR-2021-12372429 Patients will be enrolled from those attending the outpatient clinic of IRCCS Mondino Institute Pavia and Neurology Department of the University of LAquila Avezzano
Data will be collected before mAbs starting baseline-T0 and after three months T1 of mAbs treatment First Repsonder and Non-responder groups will be identified then a biochemical profiling of the two subgroups will be performed at T0 and T1
METHODS
All patients will undergo a biochemical profiling that will include analysis of
eCBome system mRNS levels of FAAH MAGL DAGL NAPE NAAA in peripheral blood mononuclear cells
plasma levels of AEA 2-AG PEA and OEA CGRP PACAP and VIP IL-1beta TNF-alpha IL-4 and IL-10 kynurenic and quinolinic acids
miR-382-5p miR-34a miR-30a and miR-155 in peripheral blood mononuclear cells
shotgun analysis of microbiota in patients faeces
Biochemical sampling will be collected between 9 and 11 am to avoid circadian rhythm influence All evaluation will be performed in migraine interictal phase
The following collection methods will be adopted
mRNA and microRNA analysis in PBMCs Blood samples will be collected within ethylenediamine tetra-acetic acid tubes with a first isolation of PBMCs and total RNA Ubiquitin C and U6 will act as housekeeping genes for genes coding for the eCBome enzymes and miRNAs
kynurenic acid and quinolinic acid AEA PEA 2-AG and OEA will be determined according to Gao published method Gao 2020 Kinurenine metabolite levels will be measured according to the method described by Fuertig Fuertig 2016
CGRP alpha PACAP-38 and VIP levels will be measured using a commercial enzyme linked immunosorbent assay
IL-1beta TNF-alpha IL-4 IL-10 cytokine will be measured by the Ella Automated Immunoassay System with a Simple Plex assay panel
Microbiome analysis after correct collection and preservation of stool specimens they will be delivered to the Translational Neurovascular Research Unit IRCCS Mondino Foundation for DNA extraction
STATISTICAL ANALYSIS Sample size calculation is defined for primary outcome MAGL expression while a power analysis is performed for the co-primary outcome FAAH expression
According to preliminary data from the work of Greco 2021 suggesting a ratio between Non-responders and Responders 23 and MAGL gene expression 810 RQ in Non-responders and 34 RQ in Responders the minimum sample size is of 88 migraine patients 53 Responders and 35 NON-Responders in order to have a confidence interval 95 and power of 80
Normality analysis will be performed to evaluate parametric or non-parametric methods
A univariate analysis will be performed to search for differences in demographic clinical and biochemical parameters between Non-Responder and Responder groups at T0 Main statistical analysis will include a multivariate approach to control for confounders The level of significance will be set at alpha 005 considering correction for multiple comparisons where appropriate
Despite the high effectiveness and tolerability of mAbs monoclonal antibodies directed against the Calcitonin gene related peptide mAbs evidence from RCTs and real-life studies demonstrates that mAbs fail in 40 of patients These patients may bear a non CGRP- dependent phenotype potentially linked to eCBome dysfunction
Primary aim is to perform a deep phenotyping of the whole cohort of migraine patients comparing the subgroups of those patients who will be Responders to mAbs treatment namely those patients who achieved a reduction of monthly migraine days 50 compared to the Non-Respoder group namely those patients who achieved a reduction of monthly migraine days 50
Neuropeptides microRNAs inflammatory cytokines and kynurenine metabolites will be evaluated These findings will allow the identification of a multibiomarkers panel signature of migraine patients resisting to specifically targeted preventive treatments and potentially unveiling other molecular targets
STUDY DESIGN
This study is part of the SPHERA project with funding from the Italian Ministry of Health GR-2021-12372429 Patients will be enrolled from those attending the outpatient clinic of IRCCS Mondino Institute Pavia and Neurology Department of the University of LAquila Avezzano
Data will be collected before mAbs starting baseline-T0 and after three months T1 of mAbs treatment First Repsonder and Non-responder groups will be identified then a biochemical profiling of the two subgroups will be performed at T0 and T1
METHODS
All patients will undergo a biochemical profiling that will include analysis of
eCBome system mRNS levels of FAAH MAGL DAGL NAPE NAAA in peripheral blood mononuclear cells
plasma levels of AEA 2-AG PEA and OEA CGRP PACAP and VIP IL-1beta TNF-alpha IL-4 and IL-10 kynurenic and quinolinic acids
miR-382-5p miR-34a miR-30a and miR-155 in peripheral blood mononuclear cells
shotgun analysis of microbiota in patients faeces
Biochemical sampling will be collected between 9 and 11 am to avoid circadian rhythm influence All evaluation will be performed in migraine interictal phase
The following collection methods will be adopted
mRNA and microRNA analysis in PBMCs Blood samples will be collected within ethylenediamine tetra-acetic acid tubes with a first isolation of PBMCs and total RNA Ubiquitin C and U6 will act as housekeeping genes for genes coding for the eCBome enzymes and miRNAs
kynurenic acid and quinolinic acid AEA PEA 2-AG and OEA will be determined according to Gao published method Gao 2020 Kinurenine metabolite levels will be measured according to the method described by Fuertig Fuertig 2016
CGRP alpha PACAP-38 and VIP levels will be measured using a commercial enzyme linked immunosorbent assay
IL-1beta TNF-alpha IL-4 IL-10 cytokine will be measured by the Ella Automated Immunoassay System with a Simple Plex assay panel
Microbiome analysis after correct collection and preservation of stool specimens they will be delivered to the Translational Neurovascular Research Unit IRCCS Mondino Foundation for DNA extraction
STATISTICAL ANALYSIS Sample size calculation is defined for primary outcome MAGL expression while a power analysis is performed for the co-primary outcome FAAH expression
According to preliminary data from the work of Greco 2021 suggesting a ratio between Non-responders and Responders 23 and MAGL gene expression 810 RQ in Non-responders and 34 RQ in Responders the minimum sample size is of 88 migraine patients 53 Responders and 35 NON-Responders in order to have a confidence interval 95 and power of 80
Normality analysis will be performed to evaluate parametric or non-parametric methods
A univariate analysis will be performed to search for differences in demographic clinical and biochemical parameters between Non-Responder and Responder groups at T0 Main statistical analysis will include a multivariate approach to control for confounders The level of significance will be set at alpha 005 considering correction for multiple comparisons where appropriate
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None