Ignite Creation Date:
2024-05-05 @ 4:51 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00329823
Status:
COMPLETED
Last Update Posted:
2006-05-25
First Post:
2006-05-23
Brief Title:
Etanercept in Hidradenitis Suppurativa
Sponsor:
University of Athens
Organization:
University of Athens
Study Overview
Official Title:
A Phase 2 Study of the Safety and Efficacy of Etanercept for the Therapy of Hydradenitis Suppurativa
Status:
COMPLETED
Status Verified Date:
2006-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug infliximab in separate cases on the grounds of a probable autoimmune predisposition of the disease The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa
Detailed Description:
Hidradenitis suppurativa is a disorder of unknown etiology Various hypotheses have implicated obesity diabetes mellitus genetic predisposition and tight clothing as probable contributing factors Although patients are presenting with suppuration of their lesions typical furuncles are absent 1 Administration of antibiotics offers transient relief of symptoms whereas therapies like androgens isotretinoin and methotrexate have failed to disclose clinical benefit 2
More than thirty out-patients with hidradenitis suppurativa are followed up at the clinic of the Immunology of Infectious Diseases of the ATTIKON University Hospital of Athens None of them is presenting with diabetes mellitus and their CD4 cell counts are within normal limits However their testing for the function of monocytes is often abnormal This test involves the isolation of monocytes and the ex vivo release of pro-inflammatory cytokines both without and after stimulation by bacterial endotoxins and lipoteichoic acid Results have shown an increased baseline secretion and poor response of monocytes after stimulation
Case reports with limited number of patients have disclosed clinical benefit of an other anti-TNF drug infliximab after one or two doses administration in hidradenitis suppurativa These reports involve retrospective results of five patients 3 or single cases 45 The rationale of the administration of etanercept in hidradenitis suppurativa is based on the following data a etanercept has been proven effective for the management of psoriasis that is considered a skin disorder with autoimmune background 6 and b laboratory findings of our patients with hidradenitis suppurativa point towards an altered immune response of their adaptive immunity 7
Tumor necrosis factor TNF is a dominant cytokine in the inflammatory process of rheumatoid arthritis Elevated levels of TNF are also found in the synovium of patients with psoriatic arthritis Etanercept is a competitive inhibitor of TNF-binding to its cell surface receptors and thereby inhibits the biological activity of TNF TNF and lymphotoxin are pro-inflammatory cytokines that bind to two distinct cell surface receptors the 55-kilodalton p55 and 75-kilodalton p75 tumor necrosis factor receptors TNFRs Both TNFRs exist naturally in membrane-bound and soluble forms Soluble TNFRs are thought to regulate TNF biological activity
TNF and lymphotoxin exist predominantly as homotrimers with their biological activity dependent on cross-linking of cell surface TNFRs Dimeric soluble receptors such as etanercept possess a higher affinity for TNF than monomeric receptors and are considerably more potent competitive inhibitors of TNF binding to its cellular receptors In addition use of an immunoglobulin Fc region as a fusion element in the construction of a dimeric receptor imparts a longer serum half-life
OBJECTIVE
The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa
RATIONALE
The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug infliximab in separate cases on the grounds of a probable autoimmune predisposition of the disease
More than thirty out-patients with hidradenitis suppurativa are followed up at the clinic of the Immunology of Infectious Diseases of the ATTIKON University Hospital of Athens None of them is presenting with diabetes mellitus and their CD4 cell counts are within normal limits However their testing for the function of monocytes is often abnormal This test involves the isolation of monocytes and the ex vivo release of pro-inflammatory cytokines both without and after stimulation by bacterial endotoxins and lipoteichoic acid Results have shown an increased baseline secretion and poor response of monocytes after stimulation
Case reports with limited number of patients have disclosed clinical benefit of an other anti-TNF drug infliximab after one or two doses administration in hidradenitis suppurativa These reports involve retrospective results of five patients 3 or single cases 45 The rationale of the administration of etanercept in hidradenitis suppurativa is based on the following data a etanercept has been proven effective for the management of psoriasis that is considered a skin disorder with autoimmune background 6 and b laboratory findings of our patients with hidradenitis suppurativa point towards an altered immune response of their adaptive immunity 7
Tumor necrosis factor TNF is a dominant cytokine in the inflammatory process of rheumatoid arthritis Elevated levels of TNF are also found in the synovium of patients with psoriatic arthritis Etanercept is a competitive inhibitor of TNF-binding to its cell surface receptors and thereby inhibits the biological activity of TNF TNF and lymphotoxin are pro-inflammatory cytokines that bind to two distinct cell surface receptors the 55-kilodalton p55 and 75-kilodalton p75 tumor necrosis factor receptors TNFRs Both TNFRs exist naturally in membrane-bound and soluble forms Soluble TNFRs are thought to regulate TNF biological activity
TNF and lymphotoxin exist predominantly as homotrimers with their biological activity dependent on cross-linking of cell surface TNFRs Dimeric soluble receptors such as etanercept possess a higher affinity for TNF than monomeric receptors and are considerably more potent competitive inhibitors of TNF binding to its cellular receptors In addition use of an immunoglobulin Fc region as a fusion element in the construction of a dimeric receptor imparts a longer serum half-life
OBJECTIVE
The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa
RATIONALE
The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug infliximab in separate cases on the grounds of a probable autoimmune predisposition of the disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None