Cytokines in Blister Fluids of Bullous Pemphigoid (BP)

NCT03856840 | Completed

• 1 other identifier: 2018/0181
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

This study investigates the differences of Eosinophil Cationic Protein, Tumor Necrosis Factor-alpha and Anti-BP180-NC16A IgG levels of blister fluids in Bullous Pemphigoid patients which appeared before and under treatment subsequently. These molecules will also be measured in blood serum before and under treatment. Changes of titers in serum and differences between blister fluids will be compared to observe whether correlation exists between them. These measures will also be compared between groups of responders and non-responders to the first-line treatment options to analyze correlation with treatment success.

Conditions

Pemphigoid, Bullous

Keywords

Pemphigoid, Bullous; Bullous Pemphigoid; Blister Fluid; Eosinophil Cationic Protein; Tumor Necrosis Factor-alpha; Anti-BP180; Disease activity; Disease severity

Outcome Measures

Primary Outcomes (3)

• Titers of Eosinophil Cationic Protein in blister fluid and blood serum

  Calculated of measurements of Eosinophil Cationic Protein (pg/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.

  14 Days

• Titers of Tumor Necrosis Factor-alpha in blister fluid and blood serum

  Calculated of measurements of Tumor Necrosis Factor-alpha (pg/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.

  14 Days

• Titers of Anti-BP180-NC18A IgG in blister fluid and blood serum

  Calculated of measurements of Anti-BP180-NC18A IgG (U/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.

  14 Days

Secondary Outcomes (8)

• Time to control of disease activity

  Up to 4 weeks

• Consolidation phase of Outcome Measures for Bullous Pemphigoid

  14 days

• Treatment Failure

  4 week

• Relapse/Flare

  Up to one year

• Bullous Pemphigoid disease severity assessment

  One day

Study Arms (1)

Bullous Pemphigoid Patients

Bullae and blood serum, which are obtained before and under treatment, will be compared in each other regardless of any condition.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All Bullous Pemphigoid patients presented to concerning clinics who accept the terms and definitions and sign consent form.

You may qualify if:

• All patiens presented to clinics who is diagnosed with Bullous Pemphigoid by findings of clinical, histopathological, Direct Immunoflorescent evaluation.
• All relapsed/flared Bullous Pemphigoid patients.
• Patients who accept the terms and conditions and sign consent form.

You may not qualify if:

• Patients who are received treatment before presenting clinics where the study is conducted.
• Patients who reject to join to study and the terms and condition
• Patients who leave the study by own decision

Sponsors & Collaborators

• Mahmut Can Koska: lead

Study Sites (2)

Istanbul Medeniyet University Goztepe Training and Research Hospital

Istanbul, Kadikoy, 37722, Turkey (Türkiye)

Location

Istanbul Training and Research Hospital

Istanbul, Samatya, 34098, Turkey (Türkiye)

Location

Related Publications (19)

• Bernard P, Antonicelli F. Bullous Pemphigoid: A Review of its Diagnosis, Associations and Treatment. Am J Clin Dermatol. 2017 Aug;18(4):513-528. doi: 10.1007/s40257-017-0264-2.

  PMID: 28247089 BACKGROUND

• Bagci IS, Horvath ON, Ruzicka T, Sardy M. Bullous pemphigoid. Autoimmun Rev. 2017 May;16(5):445-455. doi: 10.1016/j.autrev.2017.03.010. Epub 2017 Mar 8.

  PMID: 28286109 BACKGROUND

• Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013 Jan 26;381(9863):320-32. doi: 10.1016/S0140-6736(12)61140-4. Epub 2012 Dec 11.

  PMID: 23237497 BACKGROUND

• Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin. 2011 Jul;29(3):427-38, viii-ix. doi: 10.1016/j.det.2011.03.010.

  PMID: 21605808 BACKGROUND

• Marzano AV, Tedeschi A, Fanoni D, Bonanni E, Venegoni L, Berti E, Cugno M. Activation of blood coagulation in bullous pemphigoid: role of eosinophils, and local and systemic implications. Br J Dermatol. 2009 Feb;160(2):266-72. doi: 10.1111/j.1365-2133.2008.08880.x. Epub 2008 Oct 20.

  PMID: 18945300 BACKGROUND

• Engineer L, Bhol K, Kumari S, Razzaque Ahmed A. Bullous pemphigoid: interaction of interleukin 5, anti-basement membrane zone antibodies and eosinophils. A preliminary observation. Cytokine. 2001 Jan 7;13(1):32-38. doi: 10.1006/cyto.2000.0791.

  PMID: 11145840 BACKGROUND

• Provost TT, Tomasi TB Jr. Immunopathology of bullous pemphigoid. Basement membrane deposition of IgE, alternate pathway components and fibrin. Clin Exp Immunol. 1974 Oct;18(2):193-200.

  PMID: 4619597 BACKGROUND

• D'Auria L, Pimpinelli F, Ferraro C, D'Ambrogio G, Giacalone B, Bellocci M, Ameglio F. Relationship between theoretical molecular weight and blister fluid/serum ratio of cytokines and five other molecules evaluated in patients with bullous pemphigoid. J Biol Regul Homeost Agents. 1998 Jul-Sep;12(3):76-80.

  PMID: 9795835 BACKGROUND

• Giusti D, Gatouillat G, Le Jan S, Plee J, Bernard P, Antonicelli F, Pham BN. Eosinophil Cationic Protein (ECP), a predictive marker of bullous pemphigoid severity and outcome. Sci Rep. 2017 Jul 6;7(1):4833. doi: 10.1038/s41598-017-04687-5.

  PMID: 28684769 BACKGROUND

• Tedeschi A, Marzano AV, Lorini M, Balice Y, Cugno M. Eosinophil cationic protein levels parallel coagulation activation in the blister fluid of patients with bullous pemphigoid. J Eur Acad Dermatol Venereol. 2015 Apr;29(4):813-7. doi: 10.1111/jdv.12464. Epub 2014 Mar 20.

  PMID: 24650303 BACKGROUND

• D'Auria L, Pietravalle M, Mastroianni A, Ferraro C, Mussi A, Bonifati C, Giacalone B, Ameglio F. IL-5 levels in the serum and blister fluid of patients with bullous pemphigoid: correlations with eosinophil cationic protein, RANTES, IgE and disease severity. Arch Dermatol Res. 1998 Jan-Feb;290(1-2):25-7. doi: 10.1007/s004030050272. No abstract available.

  PMID: 9522998 BACKGROUND

• Dierksmeier U, Frosch PJ, Czarnetzki BM. Eosinophil chemotactic factor (ECF) in blister fluid of dermatological diseases. Br J Dermatol. 1980 Jan;102(1):43-8. doi: 10.1111/j.1365-2133.1980.tb05670.x.

  PMID: 6990957 BACKGROUND

• Ameglio F, D'Auria L, Cordiali-Fei P, Mussi A, Valenzano L, D'Agosto G, Ferraro C, Bonifati C, Giacalone B. Bullous pemphigoid and pemphigus vulgaris: correlated behaviour of serum VEGF, sE-selectin and TNF-alpha levels. J Biol Regul Homeost Agents. 1997 Oct-Dec;11(4):148-53.

  PMID: 9582615 BACKGROUND

• Murrell DF, Daniel BS, Joly P, Borradori L, Amagai M, Hashimoto T, Caux F, Marinovic B, Sinha AA, Hertl M, Bernard P, Sirois D, Cianchini G, Fairley JA, Jonkman MF, Pandya AG, Rubenstein D, Zillikens D, Payne AS, Woodley D, Zambruno G, Aoki V, Pincelli C, Diaz L, Hall RP, Meurer M, Mascaro JM Jr, Schmidt E, Shimizu H, Zone J, Swerlick R, Mimouni D, Culton D, Lipozencic J, Bince B, Grando SA, Bystryn JC, Werth VP. Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts. J Am Acad Dermatol. 2012 Mar;66(3):479-85. doi: 10.1016/j.jaad.2011.06.032. Epub 2011 Nov 5.

  PMID: 22056920 BACKGROUND

• Eming R, Sticherling M, Hofmann SC, Hunzelmann N, Kern JS, Kramer H, Pfeiffer C, Schuster V, Zillikens D, Goebeler M, Hertl M, Nast A, Orzechowski HD, Sardy M, Schmidt E, Sitaru C, Sporbeck B, Worm M. S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid. J Dtsch Dermatol Ges. 2015 Aug;13(8):833-44. doi: 10.1111/ddg.12606. No abstract available.

  PMID: 26213827 BACKGROUND

• Zhao CY, Murrell DF. Advances in understanding and managing bullous pemphigoid. F1000Res. 2015 Nov 20;4:F1000 Faculty Rev-1313. doi: 10.12688/f1000research.6896.1. eCollection 2015.

  PMID: 26918143 BACKGROUND

• Levy-Sitbon C, Barbe C, Plee J, Goeldel AL, Antonicelli F, Reguiai Z, Jolly D, Grange F, Bernard P. Assessment of bullous pemphigoid disease area index during treatment: a prospective study of 30 patients. Dermatology. 2014;229(2):116-22. doi: 10.1159/000362717. Epub 2014 Jul 5.

  PMID: 25011586 BACKGROUND

• Joly P, Roujeau JC, Benichou J, Delaporte E, D'Incan M, Dreno B, Bedane C, Sparsa A, Gorin I, Picard C, Tancrede-Bohin E, Sassolas B, Lok C, Guillaume JC, Doutre MS, Richard MA, Caux F, Prost C, Plantin P, Chosidow O, Pauwels C, Maillard H, Saiag P, Descamps V, Chevrant-Breton J, Dereure O, Hellot MF, Esteve E, Bernard P. A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study. J Invest Dermatol. 2009 Jul;129(7):1681-7. doi: 10.1038/jid.2008.412. Epub 2009 Jan 29.

  PMID: 19177141 BACKGROUND

• Feliciani C, Joly P, Jonkman MF, Zambruno G, Zillikens D, Ioannides D, Kowalewski C, Jedlickova H, Karpati S, Marinovic B, Mimouni D, Uzun S, Yayli S, Hertl M, Borradori L. Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology. Br J Dermatol. 2015 Apr;172(4):867-77. doi: 10.1111/bjd.13717.

  PMID: 25827742 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blister Fluid: Blister fluids will be obtained from all enrolled patients in specific three intervals: Before treatment, 4-7. and 8-14. days of treatment in 24 hours after they appear. Bullae of only one individual day will be selected for each interval to study if they appeared. Blood Serum: Blood serum will be obtained from all enrolled patients before treatment, seventh day of treatment and fourteen day of treatment. Obtaining blood serum from patients was added to study afterward. New ethical committee approval was received for that modification in recruitment status at May 17, 2018. Thus blood serum weren't obtained patients who were recruited before that approval. But other specimens obtained from these patients will be included study.

MeSH Terms

Conditions

Pemphigoid, Bullous

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Mehmet Salih Gurel, Professor

  Istanbul Medeniyet University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Doctor

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 27, 2019
• Study Start: January 29, 2018
• Primary Completion: May 23, 2019
• Study Completion: August 27, 2019
• Last Updated: October 4, 2019

Record last verified: 2019-10

Locations

TU (2)