Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06544018
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-05-07
Brief Title:
Circadian Rhythm Deregulation in Patients With CAPS
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Identification of Circadian Rhythm Deregulation in Patients With Cryopyrin-associated Periodic Syndrome CAPS
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
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:
ICARUS
Brief Summary:
Circadian rhythms are characterized by the physiologys adaptation to the alternation of day and night enabling to adapt to the environment These rhythms are generated by a molecular clock within each cell At the molecular level the circadian clock is based on a complex system of cell-autonomous transcription loops These exert positive and negative feedback on themselves generating cyclic transcriptional activity
In the main loop the BMAL1 transcription factor links with CLOCK or NPAS2 Neuronal PAS Domain Protein 2 to activate transcription of per12 and 3 and cryptochrome cry1 and cry2 which in turn repress BMAL1CLOCK1 transcriptional activity The BMAL1CLOCK complex also activates transcription of numerous target genes per and cry Rev-erb etc
other secondary loops refine the function of the first
Recent studies suggest that many aspects of innate immunity are controlled by circadian rhythm through inhibition of NLRP3 inflammasome activation Nevertheless the regulation of the NLRP3 inflammasome by the circadian clock has yet to be elucidated Inflammasomes are molecular platforms that control caspase-1 activation and consequently the maturation of precursors of interleukine IL-1β pro-IL-18 a pro-inflammatory cytokine Since its discovery its functions have been widely characterized as part of the innate immune response as a sensor of pathogens and danger signals extracellular ATP Adenosine triphosphate atmospheric pollutants NLRP3 nucleotide-binding domain LRR leucin-rich repeat and pyrin-containing receptor 3 has been described for its genetic association with dominant monogenic hereditary syndromes characterized by recurrent systemic inflammatory episodes in the absence of any infection or autoimmune disease known as CAPS cryopyrin-associated periodic syndrome or cryopyrinopathies which is a continuum of diseases ranging from a moderate to the most severe form of the syndrome familial cold urticaria syndrome Muckle-Wells syndrome MWS and CINCANOMID syndrome
Interestingly patients with Muckle-Wells syndrome show a circadian pattern of symptoms with a recurrent predominantly vesperal fever peak lasting a few hours and extreme fatigue on a daily basis However a molecular link between the circadian clock and CAPS pathology remains to be determined
The aim of this protocol is to identify circadian rhythm dysregulation in patients with CAPS confirmed by genetic analysis of NLRP3 to demonstrate a link between circadian clock and CAPS syndrome and to identify circadian clock regulatory pathways
In the main loop the BMAL1 transcription factor links with CLOCK or NPAS2 Neuronal PAS Domain Protein 2 to activate transcription of per12 and 3 and cryptochrome cry1 and cry2 which in turn repress BMAL1CLOCK1 transcriptional activity The BMAL1CLOCK complex also activates transcription of numerous target genes per and cry Rev-erb etc
other secondary loops refine the function of the first
Recent studies suggest that many aspects of innate immunity are controlled by circadian rhythm through inhibition of NLRP3 inflammasome activation Nevertheless the regulation of the NLRP3 inflammasome by the circadian clock has yet to be elucidated Inflammasomes are molecular platforms that control caspase-1 activation and consequently the maturation of precursors of interleukine IL-1β pro-IL-18 a pro-inflammatory cytokine Since its discovery its functions have been widely characterized as part of the innate immune response as a sensor of pathogens and danger signals extracellular ATP Adenosine triphosphate atmospheric pollutants NLRP3 nucleotide-binding domain LRR leucin-rich repeat and pyrin-containing receptor 3 has been described for its genetic association with dominant monogenic hereditary syndromes characterized by recurrent systemic inflammatory episodes in the absence of any infection or autoimmune disease known as CAPS cryopyrin-associated periodic syndrome or cryopyrinopathies which is a continuum of diseases ranging from a moderate to the most severe form of the syndrome familial cold urticaria syndrome Muckle-Wells syndrome MWS and CINCANOMID syndrome
Interestingly patients with Muckle-Wells syndrome show a circadian pattern of symptoms with a recurrent predominantly vesperal fever peak lasting a few hours and extreme fatigue on a daily basis However a molecular link between the circadian clock and CAPS pathology remains to be determined
The aim of this protocol is to identify circadian rhythm dysregulation in patients with CAPS confirmed by genetic analysis of NLRP3 to demonstrate a link between circadian clock and CAPS syndrome and to identify circadian clock regulatory pathways
Detailed Description:
None
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