Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2012 by Centre Hospitalier Universitaire de Nice
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT01538342
First received: January 13, 2012
Last updated: August 6, 2012
Last verified: January 2012
  Purpose

Psoriasis is a chronic autoimmune disorder of the skin. In this disease, the inflammatory caspases, cysteine ​​proteases involved in the processing of many proteins, are activated. Transgenic mice expressing the cleaved form of caspases by Lyn, a tyrosine kinase Src family, develop an inflammatory syndrome with the characteristics of human psoriasis.

To clarify the relationship between the cleaved form of Lyn by caspases and psoriasis, the investigators intend to develop a clinical study to analyze the expression, cleavage and activity of Lyn and the activation of caspases from skin biopsies of patients with this disease.

This study will be conducted on a cohort of patients with different forms of psoriasis (plaque, pustular and erythrodermic) and atopic dermatitis, another skin disorder associated with chronic inflammation. Thus, the investigators will evaluate the expression and activity of Lyn from skin lesion (L) and non-lesional (NL) from the same patient in parallel with the level of caspase activation and apoptotic inflammatory.

Thus, the investigators will verify that the cleavage by caspases of Lyn is associated specifically with psoriasis, as the investigators believe, or more generally to the skin inflammation. The investigators work would then define the cleavage by caspases of Lyn as a new potential marker of human psoriasis.


Condition Intervention
Psoriasis
Atopic Dermatitis
Other: 3 Biopsies
Other: 2 biopsies
Other: biopsy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

Primary Outcome Measures:
  • Cleavage of Lyn [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    The cleavage of Lyn will be determined in the different extracts of skin of patients with western blotting using an antibody specific for Lyn recognizing the native form but also the form cleaved by caspases.

  • Expression levels of Lyn [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    The expression levels of Lyn and its cleaved form will be quantified using the software MultiGauge. The investigators will also determine the level of activity of Lyn using an antibody directed against the active form phosphorylated. The level of expression of proteins of interest will be reported at the level of protein expression control (ERK2) whose expression does not vary depending on the samples (load control).

  • Specific activity of apoptotic caspases 3, 6, 7, 8 and 9, and inflammatory caspases 1, 4, and 5 [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    The investigators will determine the specific activity of apoptotic caspases 3, 6, 7, 8 and 9, and inflammatory caspases 1, 4, and 5 test microplate. The principle of this test is based on the use of a specific substrate of caspases coupled to a fluorochrome that fluoresces when it is released after the action of caspase-level target aspartate. The fluorescence emission, which is proportional to the amount of active caspase in the sample is then measured with a fluorometer.


Secondary Outcome Measures:
  • Development of a monoclonal antibodyspecific for the cleaved form of caspases by Lyn [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Development of a monoclonal antibody specific for the form cleaved by caspases of Lyn. Once obtained and validated, this tool will be especially useful for immunohistological analysis of Lyn on skin sections from patients with psoriasis. Then we can also analyze which skin cells express preferentially cleaved form of Lyn.


Estimated Enrollment: 170
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
chronic plaque psoriasis
3 biopsies: 2 lesional and 1 non-lesional
Other: 3 Biopsies
3 biopsies: 2 lesional and 1 non-lesional
pustular psoriasis
3 biopsies: 2 lesional and 1 non-lesional
Other: 3 Biopsies
3 biopsies: 2 lesional and 1 non-lesional
erythrodermic psoriasis
3 biopsies: 2 lesional and 1 non-lesional
Other: 3 Biopsies
3 biopsies: 2 lesional and 1 non-lesional
atopic dermatitis
2 biopsies: 1 lesional and 1 non-lesional
Other: 2 biopsies
Other Name: 1 lesional and 1 non-lesional
healthy patients
1 biopsy of healthy skin.
Other: biopsy
1 biopsy ok healthy skin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Psoriasis arms:

  • Plaque psoriasis and erythrodermic more than 10% of body surface area.
  • Pustular psoriasis of at least 1% of body surface.

    • Atopic dermatitis arm:Patients with atopic dermatitis has been identified and inflammatory lesions on the skin.
    • Healthy arm:People not suffering from any skin disease

Exclusion Criteria:

  • Systemic treatment of psoriasis for at least 4 weeks and / or local treatment for at least 2 weeks at the time of study entry.
  • Patient with significant infection and / or immunocompromised.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01538342

Contacts
Contact: Jean-Paul ORTONNE, PU-PH 04 92 03 64 88 ext +33 ortonne@unice.fr
Contact: Sandrine MARCHETTI, PhD 04 93 37 70 16 ext +33 Sandrine.Marchetti@unice.fr

Locations
France
Assistance Publique - Hôpitaux de Marseille Recruiting
Marseille, France, 13 005
Contact: Marie-Aleth RICHARD, PU-PH    04 91 38 79 91 ext +33    mrichard@ap-hm.fr   
Principal Investigator: Marie-Aleth RICHARD, PU-PH         
University Hospital of Nice Active, not recruiting
Nice, France, 06000
University Hospital of Toulouse Not yet recruiting
Toulouse, France, 31059
Contact: Carle PAUL, PU-PH    05 61 77 76 75 ext +33    paul.c@chu-toulouse.fr   
Principal Investigator: Carle PAUL, PU-PH         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Study Director: Jean-Paul ORTONNE, PU-PH CHU de Nice
Study Chair: Sandrine MARCHETTI, PhD Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator: Marie-Aleth RICHARD, PU-PH AP-HM
Principal Investigator: Carle PAUL, PU-PH University Hospital, Toulouse
  More Information

Additional Information:
No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT01538342     History of Changes
Other Study ID Numbers: 11-API-03
Study First Received: January 13, 2012
Last Updated: August 6, 2012
Health Authority: France: Committee for the Protection of Personnes
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Psoriasis
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Skin Diseases, Papulosquamous

ClinicalTrials.gov processed this record on July 24, 2014