Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00222183
Status:
WITHDRAWN
Last Update Posted:
2018-06-28
First Post:
2005-09-19
Brief Title:
Cutaneous Lupus Erythematosus and Elidel
Sponsor:
University of Leipzig
Organization:
University of Leipzig
Study Overview
Official Title:
Evaluation of the Therapeutic Effect and Local Tolerability of Elidel Cream 1 Pimecrolimus in Chronic Discoid Lupus Erythematosus dLE or Subacute Cutaneous Lupus Erythematosus scLE
Status:
WITHDRAWN
Status Verified Date:
2007-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Head of the study has left the institution Study never started
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This trial evaluates the therapeutic effect of Elidel pimecrolimus in comparison to the corresponding vehicle in patients with chronic discoid lupus erythematosus dLE or subacute cutaneous lupus erythematosus scLE
Detailed Description:
Lupus erythematosus is an autoimmune disease of unknown origin which is classified according to its clinical features the course and laboratory findings A rough classification divides lupus erythematosus into three subgroups
1 discoid lupus erythematosus dLE
2 subacute cutaneous lupus erythematosus scLE and
3 systemic lupus erythematosus sLEsLE
The onset of lupus erythematosus affects women three times more frequently than men with an onset between the 20th and 40th years of life It is often aggravated or triggered by multiple factors like UV-light mainly UV-A hormones thyroid diseases pregnancy oral contraceptives stress or trauma Some medications might also play a role as triggering substances for example antibiotics psychotropic drugs beta blockers procainamide diuretics piroxicam and griseofulvin
The prevalence of systemic lupus erythematosus sLEsLE is 12 to 50100000 population worldwide the incidence is 2 to 8100000 per year Skin disease is one of the most frequent clinical complaints of patients suffering from sLEsLE It has been found to occur in up to 70 of patients during the course of the disease
The interesting subgroups of LE that are part of the study population suffer from discoid lupus erythematosus dLE or subacute cutaneous lupus erythematosus scLE Fritsch 1998
Discoid lupus erythematosus is the most common form of the chronic forms of cutaneous LE It is a very chronic inflammatory disease consisting of fixed indurated erythematous papules and plaques that are often distributed on the head and neck Without intervention dLE lesions may last for many years and are associated with extensive scarring When dLE occurs on the scalp permanent scarring and alopecia may result If the initial work-up of a patient with localized lesion of dLE does not reveal evidence of sLEsLE the risk of developing sLEsLE is low about 5 When dLE lesions are generalized this risk is slightly higher However dLE lesions are not uncommon in patients with an established diagnosis of sLEsLE About 25 of sLEsLE patients will develop lesions of dLE at some time in the course of their disease Fitzpatrick 1996
Subacute cutaneous lupus erythematosus scLE was first described in the late 1970s These patients suffer from cutaneous lesions which have an eruption that is more persistent than that of acute cutaneous lupus erythematosus butterfly rash lasting weeks to months or longer The lesions of scLE consist of scaly superficial inflammatory macules patches papules and plaques that are photodistributed particularly on the upper chest and back lateral neck and dorsal arms and forearms Several different morphologic types of scLE have been described annular lesions and two types of papulosquamous lesions psoriasiform and pityriasiform About 50 of the patients with scLE will fulfil four or more criteria for the classification of sLEsLE though most of the scLE patients do not experience serious renal or CNS involvement of lupus erythematosus Typically they suffer from skin disease photosensitivity and musculoskeletal complaints Dry eyes and a dry mouth are also not uncommon Some patients with scLE experience severe manifestations of SLEsLE and thus all scLE patients should be monitored for systemic disease Fitzpatrick 1996
Frequently cutaneous complaints are of most concern to patients with scLE and dLE and thus dermatologists are generally the physicians managing this disease Broad spectrum sunscreens and sun-protective measures including lifestyle-changes and clothing are perhaps the most important initial measures Some patients respond to potent topical steroids Oral antimalarial therapy is also beneficial in many patients Less commonly used treatments include dapsone gold immunosuppressive drugs retinoids and systemic steroids
Standard treatment with potent topical corticosteroids is very effective but longtime application can provoke atrophy and fragility of the skin as well as telangiectasias erythema perstans perioral dermatitis and steroid acne Systemic resorption depending on the dosage area and way of application resulting in terms of a dysfunction of the hypothalamus-hypophysis axis has been described Korting 1992 Contact allergies are very uncommon but have been reported Lauerma et al 1993
The main concern is the skin atrophy following long-term application of topical corticosteroids Therefore the need for alternatives is evident
Pimecrolimus is an ascomycin and macrolactam derivative acting as a calcineurin inhibitor which binds calcineurin Dissemond et al 2002 The consequence of calcineurin binding is a lack of activation of both T helper cell types 1 and 2 Further effects of these compounds have been suggested on other inflammatory cells such as Langerhans cells and mast cellsbasophils Both entities dLE and scLE are characterized by B-cell activation due to affected T-cell activation and the formation of multiple autoantibodies This results among other symptoms in inflammatory infiltrates especially on the face Pimecrolimus cream is already approved for the treatment of atopic dermatitis Furthermore there have been studies in other indications like psoriasis allergic and irritant dermatitis Pimecrolimus has been developed for the potential treatment of psoriasis allergic irritant and atopic dermatitis Animal studies with tacrolimus ointment cream used for lupus dermatoses have shown to be promising Neckermann et al 2000 Meingassner et al 1997 Bochelen et al 1999 Topical tacrolimus therapy was applied to facial skin lesions in 7 cases of cutaneous lupus erythematosus cLE Three systemic LE and one discoid showed a marked regression of their skin lesions after tacrolimus therapy but three patients with discoid LE were resistant to the therapy A good response was observed for facial erythematosus lesions with edematous or telangiectatic changes in systemic LE Yoshimasu et al 2002 Furukawa et al 2002 In discoid LE with typical discoid lesions tacrolimus brought no improvement Pimecrolimus seems to be more promising than tacrolimus due to the altered skin penetration profile Topical pimecrolimus cream in contrast to corticosteroids does not provoke any skin atrophy Dissemond et al 2002 Queille-Roussel et al 2001 and might be a good alternative to the standard treatment of potent corticosteroids even if only a part of the patient population will respond to Elidel treatment
Topical formulations of pimecrolimus cream have been shown to be effective in atopic dermatitis chronic irritant hand dermatitis allergic contact dermatitis and also in psoriasis but in this case under semi-occlusive conditions Pharmacokinetic studies with pimecrolimus cream 1 indicate a consistently low systemic exposure in infants children and adults with atopic dermatitis regardless of the extent of lesions treated and of the duration of therapy These results support the twice daily administration of pimecrolimus cream in long-term use on an as needed basis with no limitation on the duration of treatment and on the extent of skin surface area treated The pimecrolimus cream 1 and the corresponding vehicle were devoid of significant irritation contact sensitization phototoxic or photoallergic potential in the standard local tolerability studies in healthy volunteers
The treatment will be without occlusion since occlusive treatment is not considered clinically relevant for the areas on the face in lupus erythematosus
Untreated lupus plaques in the same patient show equal expression of the clinical signs of erythema induration and scaling This allows the possibility to design a within-patient study to compare the various formulations of interest for efficacy and local tolerability
Systemic absorption is very low A pharmacokinetic study of patients with atopic dermatitis who applied 1 pimecrolimus cream twice daily for three weeks did not show any absorption in 72 of the cases Side effects were not observed van Leent et al 1998 a and b
In view of the biological profile a clinical hypothesis is formulated claiming that Elidel is well tolerated and effective in the treatment of cutaneous lupus erythematosus scLE and dLE This study is designed to test this hypothesis
1 discoid lupus erythematosus dLE
2 subacute cutaneous lupus erythematosus scLE and
3 systemic lupus erythematosus sLEsLE
The onset of lupus erythematosus affects women three times more frequently than men with an onset between the 20th and 40th years of life It is often aggravated or triggered by multiple factors like UV-light mainly UV-A hormones thyroid diseases pregnancy oral contraceptives stress or trauma Some medications might also play a role as triggering substances for example antibiotics psychotropic drugs beta blockers procainamide diuretics piroxicam and griseofulvin
The prevalence of systemic lupus erythematosus sLEsLE is 12 to 50100000 population worldwide the incidence is 2 to 8100000 per year Skin disease is one of the most frequent clinical complaints of patients suffering from sLEsLE It has been found to occur in up to 70 of patients during the course of the disease
The interesting subgroups of LE that are part of the study population suffer from discoid lupus erythematosus dLE or subacute cutaneous lupus erythematosus scLE Fritsch 1998
Discoid lupus erythematosus is the most common form of the chronic forms of cutaneous LE It is a very chronic inflammatory disease consisting of fixed indurated erythematous papules and plaques that are often distributed on the head and neck Without intervention dLE lesions may last for many years and are associated with extensive scarring When dLE occurs on the scalp permanent scarring and alopecia may result If the initial work-up of a patient with localized lesion of dLE does not reveal evidence of sLEsLE the risk of developing sLEsLE is low about 5 When dLE lesions are generalized this risk is slightly higher However dLE lesions are not uncommon in patients with an established diagnosis of sLEsLE About 25 of sLEsLE patients will develop lesions of dLE at some time in the course of their disease Fitzpatrick 1996
Subacute cutaneous lupus erythematosus scLE was first described in the late 1970s These patients suffer from cutaneous lesions which have an eruption that is more persistent than that of acute cutaneous lupus erythematosus butterfly rash lasting weeks to months or longer The lesions of scLE consist of scaly superficial inflammatory macules patches papules and plaques that are photodistributed particularly on the upper chest and back lateral neck and dorsal arms and forearms Several different morphologic types of scLE have been described annular lesions and two types of papulosquamous lesions psoriasiform and pityriasiform About 50 of the patients with scLE will fulfil four or more criteria for the classification of sLEsLE though most of the scLE patients do not experience serious renal or CNS involvement of lupus erythematosus Typically they suffer from skin disease photosensitivity and musculoskeletal complaints Dry eyes and a dry mouth are also not uncommon Some patients with scLE experience severe manifestations of SLEsLE and thus all scLE patients should be monitored for systemic disease Fitzpatrick 1996
Frequently cutaneous complaints are of most concern to patients with scLE and dLE and thus dermatologists are generally the physicians managing this disease Broad spectrum sunscreens and sun-protective measures including lifestyle-changes and clothing are perhaps the most important initial measures Some patients respond to potent topical steroids Oral antimalarial therapy is also beneficial in many patients Less commonly used treatments include dapsone gold immunosuppressive drugs retinoids and systemic steroids
Standard treatment with potent topical corticosteroids is very effective but longtime application can provoke atrophy and fragility of the skin as well as telangiectasias erythema perstans perioral dermatitis and steroid acne Systemic resorption depending on the dosage area and way of application resulting in terms of a dysfunction of the hypothalamus-hypophysis axis has been described Korting 1992 Contact allergies are very uncommon but have been reported Lauerma et al 1993
The main concern is the skin atrophy following long-term application of topical corticosteroids Therefore the need for alternatives is evident
Pimecrolimus is an ascomycin and macrolactam derivative acting as a calcineurin inhibitor which binds calcineurin Dissemond et al 2002 The consequence of calcineurin binding is a lack of activation of both T helper cell types 1 and 2 Further effects of these compounds have been suggested on other inflammatory cells such as Langerhans cells and mast cellsbasophils Both entities dLE and scLE are characterized by B-cell activation due to affected T-cell activation and the formation of multiple autoantibodies This results among other symptoms in inflammatory infiltrates especially on the face Pimecrolimus cream is already approved for the treatment of atopic dermatitis Furthermore there have been studies in other indications like psoriasis allergic and irritant dermatitis Pimecrolimus has been developed for the potential treatment of psoriasis allergic irritant and atopic dermatitis Animal studies with tacrolimus ointment cream used for lupus dermatoses have shown to be promising Neckermann et al 2000 Meingassner et al 1997 Bochelen et al 1999 Topical tacrolimus therapy was applied to facial skin lesions in 7 cases of cutaneous lupus erythematosus cLE Three systemic LE and one discoid showed a marked regression of their skin lesions after tacrolimus therapy but three patients with discoid LE were resistant to the therapy A good response was observed for facial erythematosus lesions with edematous or telangiectatic changes in systemic LE Yoshimasu et al 2002 Furukawa et al 2002 In discoid LE with typical discoid lesions tacrolimus brought no improvement Pimecrolimus seems to be more promising than tacrolimus due to the altered skin penetration profile Topical pimecrolimus cream in contrast to corticosteroids does not provoke any skin atrophy Dissemond et al 2002 Queille-Roussel et al 2001 and might be a good alternative to the standard treatment of potent corticosteroids even if only a part of the patient population will respond to Elidel treatment
Topical formulations of pimecrolimus cream have been shown to be effective in atopic dermatitis chronic irritant hand dermatitis allergic contact dermatitis and also in psoriasis but in this case under semi-occlusive conditions Pharmacokinetic studies with pimecrolimus cream 1 indicate a consistently low systemic exposure in infants children and adults with atopic dermatitis regardless of the extent of lesions treated and of the duration of therapy These results support the twice daily administration of pimecrolimus cream in long-term use on an as needed basis with no limitation on the duration of treatment and on the extent of skin surface area treated The pimecrolimus cream 1 and the corresponding vehicle were devoid of significant irritation contact sensitization phototoxic or photoallergic potential in the standard local tolerability studies in healthy volunteers
The treatment will be without occlusion since occlusive treatment is not considered clinically relevant for the areas on the face in lupus erythematosus
Untreated lupus plaques in the same patient show equal expression of the clinical signs of erythema induration and scaling This allows the possibility to design a within-patient study to compare the various formulations of interest for efficacy and local tolerability
Systemic absorption is very low A pharmacokinetic study of patients with atopic dermatitis who applied 1 pimecrolimus cream twice daily for three weeks did not show any absorption in 72 of the cases Side effects were not observed van Leent et al 1998 a and b
In view of the biological profile a clinical hypothesis is formulated claiming that Elidel is well tolerated and effective in the treatment of cutaneous lupus erythematosus scLE and dLE This study is designed to test this hypothesis
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