Ignite Creation Date:
2024-05-05 @ 4:39 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00285779
Status:
TERMINATED
Last Update Posted:
2018-03-21
First Post:
2006-01-31
Brief Title:
Use of Etanercept in the Treatment of Moderate to Severe Lichen Planus
Sponsor:
Stanford University
Organization:
Stanford University
Study Overview
Official Title:
A Double-Blind Randomized Multicenter Pilot Study to Evaluate the Efficacy and Safety of Etanercept 50mg SC Twice Weekly in the Treatment of Moderate to Severe Lichen Planus
Status:
TERMINATED
Status Verified Date:
2018-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Slow recruitment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose is to assess the response of subjects to etanercept as compared to placebo in treating the physical signs of mucosal and cutaneous lichen planus The investigators also wish to assess the effect of etanercept on disease-related itching pain and serious adverse events in patients with lichen planus
Detailed Description:
Lichen planus affects up to 1 of the worldwide population Recent estimates suggest approximately 044 of the US population suffers from this disease Oral or genital involvement occurs in 60-70 of patients and it may be the sole manifestation of disease in 20-30 of patients
Lichen planus is a mucocutaneous disorder that can involve the skin oral or genital mucosa conjunctiva and nails On the skin the disease presents as multiple papules which can be localized or generalized that are often extremely itchy Mucosal disease can consist of either asymptomatic plaques or extremely painful erosive lesions The disease course is unpredictable and typically lasts 1-2 years but can follow a chronic relapsing course Erosive mucosal disease is important to aggressively treat for many reasons First the associated pain can be debilitating for the patient Patients with severe oral lichen planus can become malnourished due to pain associated with eating Vulvar disease can cause dyspareunia burning pain and discharge second the disease tends to be chronic with little chance for self-resolution third erosive disease is associated with an increased risk of squamous cell carcinoma in the affected areas These cancers occur in up to 1 of patients over a 3-year period and they can be aggressive and even-life threatening for the patient if not recognized and treated early
Several lines of evidence suggest that TNF-alpha plays a role in the pathogenesis of lichen planus It has been shown that there are increased levels of TNF-alpha in the serum of these patients In addition skin and mucosal biopsies show increased TNF-alpha produced by the infiltrating lymphocytes as well as the basal keratinocytes It has been suggested that the expression of TNF-alpha receptor on the basal keratinocytes may contribute to apoptosis Also TNFR1 a TNF-alpha receptor is expressed by the infiltrating mononuclear cells as well as the keratinocytes Increased levels of soluble TNF receptors are also found in the serum of patients with lichen planus A recent report also has shown that polymorphisms in the TNF-alpha gene are associated with both oral and cutaneous lichen planus Finally thalidomide which partly functions as a potent inhibitor of TNF-alpha transcription has been shown to be effective in small case series and reports in selected patients for the treatment of oral and genital lichen planus However thalidomide is a potent teratogen and cannot be used in women of childbearing potential In addition thalidomide usage not uncommonly results in neurotoxicity which can be permanent and thus limits use of this drug Despite the evidence for a role of TNF-alpha in LP there are no reports of any TNF inhibitors being used for this disease
This is a double-blind placebo-controlled pilot study to observe the safety and efficacy of etanercept in patients with lichen planus
This study will consist of 3 periods first a double-blind period weeks 0-12 in which subjects will be randomized to etanercept 50 mg twice weekly or placebo second an open-label period weeks 12-24 in which subjects who were randomized to placebo treatment who have not achieved a complete remission will be rolled over to use etanercept at 50 mg twice weekly Subjects who previously received etanercept during weeks 0-12 who have not achieved a complete remission will be continued on etanercept at a lower dosage of 25 mg twice weekly for weeks 12-24 third an 8 week follow-up period for all subjects
Lichen planus is a mucocutaneous disorder that can involve the skin oral or genital mucosa conjunctiva and nails On the skin the disease presents as multiple papules which can be localized or generalized that are often extremely itchy Mucosal disease can consist of either asymptomatic plaques or extremely painful erosive lesions The disease course is unpredictable and typically lasts 1-2 years but can follow a chronic relapsing course Erosive mucosal disease is important to aggressively treat for many reasons First the associated pain can be debilitating for the patient Patients with severe oral lichen planus can become malnourished due to pain associated with eating Vulvar disease can cause dyspareunia burning pain and discharge second the disease tends to be chronic with little chance for self-resolution third erosive disease is associated with an increased risk of squamous cell carcinoma in the affected areas These cancers occur in up to 1 of patients over a 3-year period and they can be aggressive and even-life threatening for the patient if not recognized and treated early
Several lines of evidence suggest that TNF-alpha plays a role in the pathogenesis of lichen planus It has been shown that there are increased levels of TNF-alpha in the serum of these patients In addition skin and mucosal biopsies show increased TNF-alpha produced by the infiltrating lymphocytes as well as the basal keratinocytes It has been suggested that the expression of TNF-alpha receptor on the basal keratinocytes may contribute to apoptosis Also TNFR1 a TNF-alpha receptor is expressed by the infiltrating mononuclear cells as well as the keratinocytes Increased levels of soluble TNF receptors are also found in the serum of patients with lichen planus A recent report also has shown that polymorphisms in the TNF-alpha gene are associated with both oral and cutaneous lichen planus Finally thalidomide which partly functions as a potent inhibitor of TNF-alpha transcription has been shown to be effective in small case series and reports in selected patients for the treatment of oral and genital lichen planus However thalidomide is a potent teratogen and cannot be used in women of childbearing potential In addition thalidomide usage not uncommonly results in neurotoxicity which can be permanent and thus limits use of this drug Despite the evidence for a role of TNF-alpha in LP there are no reports of any TNF inhibitors being used for this disease
This is a double-blind placebo-controlled pilot study to observe the safety and efficacy of etanercept in patients with lichen planus
This study will consist of 3 periods first a double-blind period weeks 0-12 in which subjects will be randomized to etanercept 50 mg twice weekly or placebo second an open-label period weeks 12-24 in which subjects who were randomized to placebo treatment who have not achieved a complete remission will be rolled over to use etanercept at 50 mg twice weekly Subjects who previously received etanercept during weeks 0-12 who have not achieved a complete remission will be continued on etanercept at a lower dosage of 25 mg twice weekly for weeks 12-24 third an 8 week follow-up period for all subjects
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