Circadian Rhythm Deregulation in Patients With CAPS

NCT ID: NCT06544018

Last Updated: 2025-06-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-01

Study Completion Date

2028-11-01

Brief Summary

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Circadian rhythms are characterized by the physiology's 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 per1,2 and 3 and cryptochrome (cry1 and cry2), which in turn repress BMAL1/CLOCK1 transcriptional activity.. The BMAL1/CLOCK 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 CINCA/NOMID 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

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Conditions

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Cryopyrin Associated Periodic Syndrome Familial Cold Urticaria Muckle-Wells Syndrome CINCA Syndrome

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Multicenter, prospective, interventional, comparative, open-label, controlled study with 2 parallel arms.
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Patients with cryopyrin-associated periodic syndrome (CAPS)

Confirmed by genetic analysis of NLRP3

Group Type ACTIVE_COMPARATOR

Genetic analysis of NLRP3

Intervention Type GENETIC

Blood test for genetic analysis of NLRP3

Circadian rhythm measurement

Intervention Type DEVICE

Wear a Withings Pulse HR (heart rate) actigraphic watch 24 hours a day for 1 month to define circadian rhythm

Saliva sampling

Intervention Type BIOLOGICAL

Saliva sampling for salivary melatonin determination

Questionnaire

Intervention Type OTHER

Questionnaire to determine chronotype

AIDAI score

Intervention Type OTHER

Disease activity score using AIDAI score (only for patients in the CAPS group) AIDAI : AUTO-INFLAMMATORY DISEASE ACTIVITY INDEX

Blood sampling

Intervention Type BIOLOGICAL

1. Inflammatory cytokines measurement : IL1-beta (Interleukin-1) and IL-18.
2. Molecular characterization of circadian clock signaling pathways

Control group

Healthy participant (absence of CAPS, verified by NLRP3 gene analysis) living in the same household as a CAPS participant included in the protocol

Group Type PLACEBO_COMPARATOR

Genetic analysis of NLRP3

Intervention Type GENETIC

Blood test for genetic analysis of NLRP3

Circadian rhythm measurement

Intervention Type DEVICE

Wear a Withings Pulse HR (heart rate) actigraphic watch 24 hours a day for 1 month to define circadian rhythm

Saliva sampling

Intervention Type BIOLOGICAL

Saliva sampling for salivary melatonin determination

Questionnaire

Intervention Type OTHER

Questionnaire to determine chronotype

Blood sampling

Intervention Type BIOLOGICAL

1. Inflammatory cytokines measurement : IL1-beta (Interleukin-1) and IL-18.
2. Molecular characterization of circadian clock signaling pathways

Interventions

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Genetic analysis of NLRP3

Blood test for genetic analysis of NLRP3

Intervention Type GENETIC

Circadian rhythm measurement

Wear a Withings Pulse HR (heart rate) actigraphic watch 24 hours a day for 1 month to define circadian rhythm

Intervention Type DEVICE

Saliva sampling

Saliva sampling for salivary melatonin determination

Intervention Type BIOLOGICAL

Questionnaire

Questionnaire to determine chronotype

Intervention Type OTHER

AIDAI score

Disease activity score using AIDAI score (only for patients in the CAPS group) AIDAI : AUTO-INFLAMMATORY DISEASE ACTIVITY INDEX

Intervention Type OTHER

Blood sampling

1. Inflammatory cytokines measurement : IL1-beta (Interleukin-1) and IL-18.
2. Molecular characterization of circadian clock signaling pathways

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

Patient with CAPS group :

* Patients aged 6 and over
* Participant with CAPS confirmed by NLRP3 genetic analysis
* Weight greater than or equal to 25 Kg
* Parents/guardians who have been informed of the study and have signed a consent form.
* Patient affiliated to a social security scheme

Control group (healthy participant):

* Participant aged 6 and over
* Weight greater than or equal to 25 Kg
* Participant living in the same household as a subject with CAPS genetically confirmed by NLRP3 analysis and included in the protocol
* Participant with no CAPS (a priori) who consents to NLRP3 genetic analysis
* Parents/guardians who have been informed of the study and have signed a consent form.
* Participant who has been informed of the study and has agreed to take part
* Participant affiliated to a social security scheme

Exclusion Criteria

Patient with CAPS group :

* Patients with chronic sleep disorders (narcolepsy, hypersomnia) requiring medication (sleeping pills, melatonin).
* Patients with sleep apnea syndrome
* Patients working regular night shifts or alternating day and night shifts
* Pregnant or breast-feeding women
* Parents with an infant under 6 months of age
* Patient participating in another interventional drug study
* Deprivation of civil rights (curators, guardianship, safeguard of justice)

Control group (healthy participant):

* Participants with a chronic illness (ALD beneficiaries)
* Participants with chronic sleep disorders (narcolepsy, hypersomnia) requiring medication (sleeping pills, melatonin)
* Participants working regular night shifts or alternating day and night shifts
* Pregnant or breast-feeding women
* Parents with an infant under 6 months of age
* Participant participating in another interventional drug study
* Deprivation of civil rights (curators, guardianship, safeguard of justice)
Minimum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hôpital Femme-Mère-Enfant (HCL)

Bron, , France

Site Status

Hôpital Claude Huriez (CHU de Lille)

Lille, , France

Site Status

Hôpital de la Croix-Rousse (HCL)

Lyon, , France

Site Status

Hôpital Edouard Herriot (HCL)

Lyon, , France

Site Status

Hôpital Tenon (AP-HP)

Paris, , France

Site Status

Hôpital Kremlin-Bicêtre (AP-HP)

Paris, , France

Site Status

Countries

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France

Central Contacts

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Alexandre Alexandre, PR

Role: CONTACT

04 27 85 61 26 ext. 33

Samira Plassart

Role: CONTACT

04 27 85 54 42 ext. 33

Facility Contacts

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Alexandre Belot, MD;PhD

Role: primary

04 27 85 61 26 ext. 33

Éric HACHULLA, MD;PhD

Role: primary

Yvan Jamilloux, MD;PhD

Role: primary

Thomas Barba, MD

Role: primary

Sophie Georgin-Lavialle, MD;PhD

Role: primary

01 56 01 60 77 ext. 33

Isabelle Koné-Paut, MD;PhD

Role: primary

01 45 21 32 46

Other Identifiers

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2023-A01088-37

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL23_0417

Identifier Type: -

Identifier Source: org_study_id

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