Ignite Creation Date:
2024-05-06 @ 7:11 PM
Last Modification Date:
2024-10-26 @ 3:02 PM
Study NCT ID:
NCT05925790
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2023-05-28
Brief Title:
Clinical Phenotypes in Pericarditis IL-1RA Antibodies and suPAR Levels
Sponsor:
ASST Fatebenefratelli Sacco
Organization:
ASST Fatebenefratelli Sacco
Study Overview
Official Title:
Observational Study on Anti-interleukin-1 Receptor Antagonist Antibodies and Soluble Urokinase Plasminogen Activator Receptor suPAR in Pericarditis PERIPLO PERicarditis IL-1 RA Antibodies and suPAR Levels Observational Study
Status:
RECRUITING
Status Verified Date:
2024-07
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:
PERIPLO
Brief Summary:
This study aims to investigate the pathophysiology of recurrent pericarditis RP by testing for neutralizing autoantibodies against interleukin-1 receptor antagonist IL-1RA and measuring soluble urokinase plasminogen activator receptor suPAR levels The hypothesis is that these tests will provide insights into both the inflammatory and non-inflammatory phenotypes of RP shedding light on the underlying mechanisms The study will assess the correlation between antibody levels suPAR levels and markers of cardiac damage and inflammation Longitudinal testing during acute episodes and intercritical phases is also planned The results may guide the use of anakinra an IL-1 receptor antagonist in specific clinical scenarios and optimize treatment strategies for RP
Detailed Description:
Recurrent pericarditis RP is a complex challenging condition which significantly impacts patients quality of life both from the physical and emotional point of view and can lead to dangerous complications such as cardiac tamponade and constrictive pericarditis Moreover patients experiencing several recurrences also tend to need substantial healthcare resources without necessarily experiencing clinical improvement Understanding more into details the pathophysiology underlying RP is certainly of pivotal importance for optimizing workup strategies and treatment protocols It is now recognized that pericarditis stems from a bidirectional cross-talk between environmental triggers and the innate and adaptive immune systems in a genetically susceptible host with a central role of the pro-inflammatory agonistic molecule IL-1 IL-1α and IL-1β and the so-called inflammasome
Neutralizing autoantibodies have been identified targeting the endogenous interleukin-1 receptor antagonist IL-1RA in conditions characterized by severe systemic inflammation such as myocarditis after Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2 vaccination Coronavirus Disease COVID-19 and Multisystem Inflammatory Syndrome MIS-C Therefore it is possible to hypothesize that testing patients with RP for these antibodies might add significant insights into the knowledge of the pathophysiology of this condition This may help uncover different underlying mechanisms with similar clinical presentations New mechanisms involving hyperphosphorylation of IL-1RA precede peripheral immune tolerance breakdown which may also contribute to certain pericarditis phenotypes
Therefore it is possible to hypothesize that IL-1RA antibody testing could provide important information to better profile RP patients with an inflammatory phenotype as indicated by common biochemical markers like CRP and those with a complicated clinical course These patients often exhibit marked activation of the IL-1 signaling pathway and IL-1RA antibody testing may help uncover underlying mechanisms and improve their characterization Given the negative correlation between neutralizing antibodies against IL-1RA and low circulating levels of IL-1RA and markers of cardiac damage and inflammation testing these antibodies in RP might be of value High titers of IL-1RA antibodies in RP may indicate uncontrolled activation of the IL-1 pathway shedding light on why some patients experience recurrences when tapering treatment with the naturally occurring IL-1 receptor antagonist anakinra Testing these IL-1RA antibodies in other types of pericarditis could also help explore their correlation with clinical phenotypes including presentation clinical course and response to treatment strategies Key exclusion criteria include pericarditis secondary to specific etiologies except post-cardiac injury history of immunosuppression and any clinical conditions that may influence the results
Additionally suPAR testing can complementarily highlight chronic low-grade inflammation which may underlie certain pericarditis cases that do not exhibit an overt inflammatory phenotype eg normal CRP but are challenging to manage
Longitudinal testing of patients during acute episodes and intercritical phases is planned if feasible
In both IL-1RA antibody and suPAR testing this study aims to provide more accurate markers compared to commonly used markers for the inflammatory phenotype and potentially uncover unknown pathophysiological mechanisms Currently there is a lack of literature on this topic
The results of this study may provide a rationale for the selective use of anakinra in specific clinical scenarios andor guide the evaluation of its dosing with an individualized approach
Neutralizing autoantibodies have been identified targeting the endogenous interleukin-1 receptor antagonist IL-1RA in conditions characterized by severe systemic inflammation such as myocarditis after Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2 vaccination Coronavirus Disease COVID-19 and Multisystem Inflammatory Syndrome MIS-C Therefore it is possible to hypothesize that testing patients with RP for these antibodies might add significant insights into the knowledge of the pathophysiology of this condition This may help uncover different underlying mechanisms with similar clinical presentations New mechanisms involving hyperphosphorylation of IL-1RA precede peripheral immune tolerance breakdown which may also contribute to certain pericarditis phenotypes
Therefore it is possible to hypothesize that IL-1RA antibody testing could provide important information to better profile RP patients with an inflammatory phenotype as indicated by common biochemical markers like CRP and those with a complicated clinical course These patients often exhibit marked activation of the IL-1 signaling pathway and IL-1RA antibody testing may help uncover underlying mechanisms and improve their characterization Given the negative correlation between neutralizing antibodies against IL-1RA and low circulating levels of IL-1RA and markers of cardiac damage and inflammation testing these antibodies in RP might be of value High titers of IL-1RA antibodies in RP may indicate uncontrolled activation of the IL-1 pathway shedding light on why some patients experience recurrences when tapering treatment with the naturally occurring IL-1 receptor antagonist anakinra Testing these IL-1RA antibodies in other types of pericarditis could also help explore their correlation with clinical phenotypes including presentation clinical course and response to treatment strategies Key exclusion criteria include pericarditis secondary to specific etiologies except post-cardiac injury history of immunosuppression and any clinical conditions that may influence the results
Additionally suPAR testing can complementarily highlight chronic low-grade inflammation which may underlie certain pericarditis cases that do not exhibit an overt inflammatory phenotype eg normal CRP but are challenging to manage
Longitudinal testing of patients during acute episodes and intercritical phases is planned if feasible
In both IL-1RA antibody and suPAR testing this study aims to provide more accurate markers compared to commonly used markers for the inflammatory phenotype and potentially uncover unknown pathophysiological mechanisms Currently there is a lack of literature on this topic
The results of this study may provide a rationale for the selective use of anakinra in specific clinical scenarios andor guide the evaluation of its dosing with an individualized approach
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