Role of Chemokine and Chemokine Receptor in Psoriasis

NCT ID: NCT03302390

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-04-17
• Study Completion Date: 2018-04-13

Brief Summary

This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that chemokine and chemokine receptor play important roles in psoriasis and establishment of human skin xenograft mouse model provide excellent platform to test the hypothesis.

Detailed Description

Chemokines belongs to a large group of small chemotactic proteins (8-11 kilodaltons in size). Upon engagement of chemokine, chemokine receptor can activate downstream intracellular signaling pathways and results in diverse cellular processing such as cytoskeleton reorganization and cell locomotion. Chemokines are chemoattractant factors and can stimulate directional migration of all classes of leukocytes such as T cells. Epidermal keratinocytes in the skin are able to express multiple chemokines that can attract certain leukocytes, such as T cells or dendritic cells (DCs), to migrate to the epidermis. Psoriasis is a type of skin inflammatory diseases that results in misregulated immune system including immune cell infiltration. Keratinocyte secreted chemokine and chemokine receptor on leukocytes have been known to involve in the pathogenesis of psoriasis. However, it is not very clear how chemokines are regulated in keratinocytes and the binding of chemokine to receptor on leukocytes controls the pathogenesis of psoriasis. To better understand the immune regulation of chemokine and chemokine receptor in the molecular mechanism and pathogenesis of psoriasis, the investigators plan to establish human psoriasis skin xenograft mouse model that involves graft of human skin onto immune deficient mice. The human skin, including lesional and non-lesional skins, has been proven to be acceptable to the SCID mice and the phenotype can maintain for a number of months. The advantage of the xenograft model is to that it can preserve the full complexity of human diseases and thus resembles the pathogenesis of human diseases. This model has also been shown with constant efficacy of anti-psoriasis drug in comparison with clinical practice. Thus, this mouse model has great value to help the investigators understand how chemokine and immune cells are regulated in psoriasis. Of particular note is that this model can be used to test therapeutic drug before introduce them into clinical trial.

Conditions

Psoriasis

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Biopsy of Skin with Psoriasis

Shave biopsy of psoriasis lesion

Shave Biopsy of Psoriasis Lesion

Intervention Type: PROCEDURE

The investigator will take about 0.5x0.5 inch square section of skin from the psoriasis lesion. To numb the skin, the subject will receive a small injection of 0.5% lidocaine HCl 5mg/mL with 1:200,000 mcg/mL epinephrine solution as per standard shave biopsy protocol. The shaving instrument has a blade that will shave off a superficial piece of skin that is less than \<3mm in thickness. After 14 days, the subject will return to make sure that the skin biopsy site has healed properly. The piece of skin that is removed will be grafted onto the back of an immunocompromised SCID mouse. An approved IACUC protocol covering this procedure will be in place prior to engraftment.

Interventions

Shave Biopsy of Psoriasis Lesion

The investigator will take about 0.5x0.5 inch square section of skin from the psoriasis lesion. To numb the skin, the subject will receive a small injection of 0.5% lidocaine HCl 5mg/mL with 1:200,000 mcg/mL epinephrine solution as per standard shave biopsy protocol. The shaving instrument has a blade that will shave off a superficial piece of skin that is less than \<3mm in thickness. After 14 days, the subject will return to make sure that the skin biopsy site has healed properly. The piece of skin that is removed will be grafted onto the back of an immunocompromised SCID mouse. An approved IACUC protocol covering this procedure will be in place prior to engraftment.

Intervention Type: PROCEDURE

Other Intervention Names

shave biopsy; biopsy; injection, lidocaine HCl with epinephrine

Eligibility Criteria

Inclusion Criteria

• Subjects 18 years of age or greater
• Subjects need to fulfill the diagnostic evidence of psoriasis with or without psoriatic arthritis
• Subject may take the following medicines: NSAID, hydroxychloroquine, sulfasalazine, prednisone (<10 mg/day), Methotrexate (10 mg/week)
• Subject needs to stop topical skin preparations other than emollients in one small plaque of psoriasis for 3-4 wks from where the shave biopsy will be taken
• Willing and able to provide informed consent in English

Exclusion Criteria

• Subjects less than 18 years old
• no clinical evidence of psoriatic skin
• Subjects with contraindications for biopsy, and patients receiving anticoagulants
• Subjects with active hepatitis B or Hepatitis C infection
• Subjects with concomitant inflammatory diseases such as inflammatory bowel disease, gout
• Subjects who are taking the following systemic biological therapies for psoriasis: cyclosporine, methotrexate, prednisone, acitretin, sulfasalazine, certolizumab, etanercept, adalimumab, infliximab, golimumab, secukinumab, ustekinumab, and apremilast. Other systemic medications may exclude the subject from the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel Hwang, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

UC Davis

Sacramento, California, United States

Countries

United States

Other Identifiers

5R01AR063091

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1015909

Identifier Type: -

Identifier Source: org_study_id