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Trial record 55 of 1729 for:    Recruiting, Not yet recruiting, Available Studies | Autoimmunity

Prospective Analysis of the Th17 Cellular Response in Pemphigus Vulgaris Patients

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ClinicalTrials.gov Identifier: NCT04096222
Recruitment Status : Recruiting
First Posted : September 19, 2019
Last Update Posted : September 19, 2019
Sponsor:
Collaborators:
Hospital General de Mexico
Hospital General Dr. Manuel Gea González
Information provided by (Responsible Party):
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Brief Summary:
This study will evaluate the pattern of Th17 immune response throughout pemphigus treatment. Skin and serum samples will be taken at the moment of enrollment and at the moment the subject reaches a 75% improvement on disease activity.

Condition or disease
Pemphigus Vulgaris Bullous Dermatoses Autoimmune Diseases

Detailed Description:

Pemphigus is an autoimmune disease characterized by production of autoantibodies against desmogleins 1 and 3, which are part of the epidermis desmosomes. The first line of treatment are corticosteroids with or without the use of adjuvants (e.g. azathioprine, mycophenolate or rituximab). T lymphocytes are responsible for the initiation and maturation of the humoral response and the B cell activation required for the production of autoantibodies. In the last decade, the Th17 immune response has been implicated in the pathogenesis of pemphigus. Recently, the existence of tertiary lymphoid organ-like structures within the skin lesions was suggested. This structures contain T lymphocytes, B lymphocytes and plasma cells; these cells interact and create a local microenvironment for the production of autoantibodies. Most of the T cells in this structures are T helper CD4+ and express IL-21, and half of them produce IL-17.

In this study the investigators aim to evaluate prospectively the Th17 and T regulatory immune response in the lesional skin and serum of active pemphigus subjects that are treated with corticosteroids with or without adjuvants. The investigators will study skin and serum due to the difference of lymphocytes and cytokines in both tissues. The primary hypothesis is: "the subjects who receive corticosteroids with or without adjuvants and who reach a 75% of improvement (measured by the pemphigus disease area index) in comparison to the enrollment visit will have a decrease in Th17 immune response (IL-23).

The investigators will use descriptive statistics, association and correlation test of hypothesis.


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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Prospective Analysis of the Th17 Cellular Response in Pemphigus Vulgaris Patients Treated With Corticosteroids and Optional Adjuvants
Estimated Study Start Date : September 15, 2019
Estimated Primary Completion Date : March 28, 2023
Estimated Study Completion Date : March 28, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus

Group/Cohort
Pemphigus subjects
Subjects with the diagnosis of pemphigus and with active disease in the skin will be invited to participate. After informed consent, at the enrollment visit the following interventions will be done: 1) two 4 mm punch biopsies in a target lesion, 2) A 10 ml blood sample will be taken, 3) photographs of the subject, 4) demographic, disease, comorbidity and treatment data will be documented, 5) PDAI and ABSIS,6) Morisky medication adherence measure with 8 items (MMAS-8). The subject will come to follow-up visits every 6 weeks +- 2 weeks. In these visits we will take photographs, perform activity scales, document treatment and MMAS-8. The termination visit will take place when the subject reaches a 75% in PDAI scale or after one year of follow up and the following interventions will be done: 1) two 4 mm punch biopsies in the same target lesion, 2) A 10 ml blood sample will be taken, 3) photographs of the subject, 4) treatment data will be documented, 5) PDAI and ABSIS, and 6) MMAS-8



Primary Outcome Measures :
  1. percentage change of IL-23 level in skin lesions [ Time Frame: variable, 1 month to 1 year ]
    The level of IL-23 mRNA from skin biopsies at the time of enrollment and when the subject reaches 75% of PDAI improvement or after a year of follow-up (termination visit). The percentage of change in these two determinations will be calculated.


Other Outcome Measures:
  1. Pemphigus Disease Area Index (PDAI) [ Time Frame: variable, 1 month to 1 year ]
    PDAI has a total of 0-263 points, 250 are related to activity and 13 to damage. Disease severity is considered as follows: 1) moderate <= 14 points; b) significative 15-44 points; and c) extensive >=45

  2. Disease activity [ Time Frame: variable, 1 month to 1 year ]
    Measured with Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). PDAI has a total of 0-263 points, 250 are related to activity and 13 to damage. ABSIS has a total score of 0-206.

  3. Treatment [ Time Frame: variable, 1 month to 1 year ]
    The medications and doses used since the diagnosis and during the study

  4. percentage change of TH17 cytokines levels [ Time Frame: variable, 1 month to 1 year ]
    The level of IL-17a, IL-21, IL-22 and IL-23 mRNA from skin biopsies and luminometry determination of serum levels at the time of enrollment and when the subject reaches 75% of PDAI improvement or after a year of follow-up (termination visit). The percentage of change in these two determinations will be calculated.

  5. percentage change of Th17 chemokines levels [ Time Frame: variable, 1 month to 1 year ]
    The level of CCL20 and CXCL8 mRNA from skin biopsies and luminometry determination of serum levels at the time of enrollment and when the subject reaches 75% of PDAI improvement or after a year of follow-up (termination visit). The percentage of change in these two determinations will be calculated.

  6. Proportion of Th17 and Treg populations on skin biopsies [ Time Frame: variable, 1 month to 1 year ]
    Enrollment and termination biopsies will be processed for immunohistochemistry for TH17 subsets (CD+IL17a+) and Treg subset (CD25+Foxp3+). The proportion of both subsets will be quantified with specialized software.

  7. Level of Th17 cytokines [ Time Frame: variable, 1 month to 1 year ]
    Determinations at the moment of enrollment and at the termination visit in skin (RT-PCR) and serum (luminometry)

  8. Level of Treg cytokines [ Time Frame: variable, 1 month to 1 year ]
    Determinations at the moment of enrollment and at the termination visit in skin (RT-PCR) and serum (luminometry)

  9. Morisky scale of medication adherence [ Time Frame: variable, 1 month to 1 year ]
    On every visit the patient will answer the Morisky scale of medication adherence with 8 items. Every item has a value of one. The degree of adherence is considered as follows: a) low 0-5 points; b) moderate 6-7 points; c) high 8 points.

  10. P-glycoprotein transporter activity in mononuclear peripheral cells [ Time Frame: variable, 1 month to 1 year ]
    The activity will be a measure of the percentage of efflux of daunorubicin ar 37°C. It will be measured at the moment of enrollment and at the termination visit

  11. Percentage of Th17 peripheral cells with expression of P-glycoprotein on the surface [ Time Frame: variable, 1 month to 1 year ]
    Cells with the phenotype IL-17a+CCR6+CXR3hiCCR4loCCR10-CD161+PGP+ will be measured with flow cytometry at the moment of enrollment and at the termination visit

  12. Levels of anti-desmogleins 1 and 3 [ Time Frame: variable, 1 month to 1 year ]
    Levels will be measures with an ELISA assay at the moment of enrollment and at the termination visit

  13. Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) [ Time Frame: variable, 1 month to 1 year ]
    ABSIS has a total score of 0-206. Disease severity is considered as follows: 1) moderate <= 16 points; b) significative 17-52 points; and c) extensive >=53

  14. Level of Treg chemokines [ Time Frame: variable, 1 month to 1 year ]
    Determinations at the moment of enrollment and at the termination visit in skin (RT-PCR) and serum (luminometry)

  15. Level of Th17 chemokines [ Time Frame: variable, 1 month to 1 year ]
    Determinations at the moment of enrollment and at the termination visit in skin (RT-PCR) and serum (luminometry)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects with the diagnosis of pemphigus who are 18 or older and who have curent skin activity and will receive treatment with corticosteroids with or without adjuvants. At the moment of enrollment subjects shoould not be pregnant, have concurrent autoimmune diseases with skin lesions (eg cutaneous lupus), cancer or infectious diseases.
Criteria

Inclusion Criteria:

  1. Current cutaneous activity of pemphigus
  2. Subjects will be treated with corticosteroids with or without adjuvants
  3. Accept and sign the informed consent

Exclusion Criteria:

  1. Pregnancy
  2. Concurrent autoimmune diseases with skin lesions
  3. Concurrent diagnosis of cancer
  4. Concurrent active infectious disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04096222


Contacts
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Contact: Luis Guillermo Llorente Peters, MD 525554870900 ext 2603 luisllorentepeters57@gmail.com
Contact: Alba Cicero Casarrubias, MD 525554870900 ext 2604 albcicero@gmail.com

Locations
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Mexico
Hospital General de Mexico Not yet recruiting
Mexico City, Mexico, 06720
Hospital General Dr. Manuel Gea González Not yet recruiting
Mexico City, Mexico, 14080
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Recruiting
Mexico City, Mexico, 14080
Contact: Luis Guillermo Llorente Peters, MD    525554870900 ext 2603    luisllorentepeters57@gmail.com   
Contact: Alba Cicero Casarrubias, MD    525554870900 ext 2604    albcicero@gmail.com   
Sponsors and Collaborators
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Hospital General de Mexico
Hospital General Dr. Manuel Gea González
Investigators
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Principal Investigator: Luis Guillermo Llorente Peters, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications:
Murrell DF, Peña S, Joly P, Marinovic B, Hashimoto T, Diaz LA, Sinha AA, Payne AS, Daneshpazhooh M, Eming R, Jonkman MF, Mimouni D, Borradori L, Kim SC, Yamagami J, Lehman JS, Saleh MA, Culton DA, Czernik A, Zone JJ, Fivenson D, Ujiie H, Wozniak K, Akman-Karakaş A, Bernard P, Korman NJ, Caux F, Drenovska K, Prost-Squarcioni C, Vassileva S, Feldman RJ, Cardones AR, Bauer J, Ioannides D, Jedlickova H, Palisson F, Patsatsi A, Uzun S, Yayli S, Zillikens D, Amagai M, Hertl M, Schmidt E, Aoki V, Grando SA, Shimizu H, Baum S, Cianchini G, Feliciani C, Iranzo P, Mascaró JM Jr, Kowalewski C, Hall R, Groves R, Harman KE, Marinkovich MP, Maverakis E, Werth VP. Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts. J Am Acad Dermatol. 2018 Feb 10. pii: S0190-9622(18)30207-X. doi: 10.1016/j.jaad.2018.02.021. [Epub ahead of print]

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Responsible Party: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
ClinicalTrials.gov Identifier: NCT04096222     History of Changes
Other Study ID Numbers: 3012
First Posted: September 19, 2019    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:
pemphigus
Th17
IL-23
IL-17
autoimmune bullous disease
Additional relevant MeSH terms:
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Pemphigus
Skin Diseases
Skin Diseases, Vesiculobullous
Autoimmune Diseases
Immune System Diseases