Ignite Creation Date:
2024-05-05 @ 6:35 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00509535
Status:
COMPLETED
Last Update Posted:
2007-07-31
First Post:
2007-07-30
Brief Title:
Prospective Randomized Double Blind Comparative Study on the Use of Two Creams in Xerosis Atopic Probands
Sponsor:
LOreal
Organization:
LOreal
Study Overview
Official Title:
Prospective Randomized Double Blind Comparative Study on the Use of Two Creams in Xerosis Atopic Probands Biomedical Findings With Vitreoscilla Filiformis
Status:
COMPLETED
Status Verified Date:
2007-07
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:
Atopic dermatitis AD a chronic and relapsing inflammatory skin disease is associated with elevated IgE levels and Th2 responses It is currently believed that non-pathogenic bacteria modulate intestinal immune responses avoiding the development of allergic diseases However effects of oral probiotics on AD could not be reproduced in all studies and direct immuno-modulation of the skin associated immune response by non-pathogenic bacteria has not been investigated so far We therefore performed a double blind placebo controlled clinical study on the effects of an ointment containing 5 extracts of the non-pathogenic bacteria Vitreoscilla filiformis on AD Seventy-five AD patients 6-70 years of age were randomized to receive either Vitreoscilla filiformis ointment 5 or vehicle ointment daily for 30 days Efficacy evaluations including the Score of Atopic Dermatitis SCORAD transepidermal water loss assessement of microflora and the patient assessment of itch and loss of sleep occurred at baseline day 15 and day 29
Detailed Description:
Atopic dermatitis AD is a chronically relapsing inflammatory skin disease and often coexists with other atopic diseases such as allergic rhinitis conjunctivitis and asthma Biedermann and Röcken 1999 Biedermann et al 2001 2004 2006 Leung et al 2000 2003a 2003b Even though the immune pathology of AD is not precisely understood today the new concept of atopic dermatitis pathology is based on a large set of data In most patients with AD dry skin and dysfunction of the epidermal barrier is found As an important prove of concept the loss of function mutation of the epidermal protein filaggrin impairing skin barrier function was found and can be detected in about 15 of kaukasian AD patients Palmer et al 2006 As a consequence patients with AD are predisposed to develop sensitizations dominated by a Th2 immune phenotype Hudson 2006
Independently of the filaggrin study it was demonstrated earlier that a disrupted barrier function of the stratum corneum is present in atopics not only in involved skin but also in uninvolved dry skin facilitating permeation of various environmental substances into the skin Berardesca et al 1990 Werner et al 1985 Watanabe et al 1991 Loden et al 1992 As a biomarker an increased level of transepidermal water loss TEWL can be demonstrated Tagami et al 1985 Ghadially et al 1996 Various functional and morphological studies on atopic xerosis that clinically appeared without inflammation demonstrated that cellular inflammation is already present in atopic skin and a key and initial step in the development of atopic dermatitis Watanabe et al 1991 Uehara et al 1984 In fact barrier dysfunction atopic immune dysregulation and atopic dermatitis pathogenesis are not independent events but closely linked Biedermann 2006 Hudson 2006 Th2 lymphocytes dominate the atopic immune phenotype and are the underlying cell type responsible for the induction if IgE antibodies Biedermann et al 1999 2004 Barrier dysfunction predisposes for the development of Th2 lymphocytes and Th2 cells are the first cell type invading atopic skin initiating inflammation and the inflammatory vicious circle of inflammation Biedermann 2002 2004 Lametschwandtner et al 2004 Günther et al 2005 Next to Th2 lymphocytes in atopic dermatitis skin lesions infiltrates of eosinophils and cells of the mononuclear phagocyte lineage are found
The altered skin structure of people with atopic predisposition allows increased penetration of allergens and irritative substances Roll et al 2004 Hudson 2006 Many studies have shown that the extent of S aureus colonization correlates with AD disease activity Cho et al 2001 Biedermann 2006 In more than 90 of AD patients a massive skin colonization with S aureus up to 107cfucm2 of lesional skin can be found Matsui et al 2000 A prerequisite for bacterial colonisation are the genuine barrier dysfunction mechanical disruption of the barrier and trigger of inflammation scratching alkaline pH decreased IgA secretion through sweat production predominant Th2 cells inhibiting anti-infectious immune responses and reduced antimicrobial peptides all representing important pathophysiological features leading to the disruption of the primary skin defense system Biedermann et al 2001 BiedermannRöcken 2001 Biedermann et al 2002 Biedermann 2006 Howell 2005 Rieg 2005
Among several microbes colonising the skin the bacterium Staphylococcus aureus S aureus may play the most important role in the pathogenesis of dermatitis of atopic people Biedermann 2006 This colonization is observed not only in the involved inflammatory skin but also in the non involved dry skin The ratio Staphylococcus aureus Staphylococcus epidermidis is inverse in comparison to healthy skin Many studies have shown that the extent of S aureus colonization correlates with AD disease intensity Cho et al 2001
Reduced expression of antimicrobial peptides was demonstrated for AD skin and favours colonization with S aureus Ong et al N Engl J Med 2002 Howell et al Immunity 200624341-8 Rieg et al JI 2006 In addition dry skin may by itself allow colonization with bacteria such as S aureus Decreased levels of sphingosine which has antimicrobial properties and the fact that S aureus itself stimulates the hydrolysis of ceramides by bacterial derived ceramidase in atopic skin add the dysfunction of the immune barrier in AD Arikawa et al 2002 Kita et al 2002 The cell membrane of S aureus contains adhesins for epidermal and dermal laminin and fibronectin allowing attachemment of S aureus to the skin and these docking positions for S aureus are uncovered in lesional skin Cho et al 2001 The precise mechanism by which S aureus gains access to the dermis is unknown but it is suggested that again IL-4 produced by T helper type 2 cells induces fibronectin synthesis which in combination with plasma exsudation of fibrinogen allows S aureus to bind to the skin Moreover S aureus is able to encase itself in a kind of biofilm composed of a hydrated matrix of polysaccharides glycocalix and proteins which supports cell adhesion Akiyama et al 2003 After colonization S aureus contributes to skin inflammation eg by secreting toxins and an array of so called pathogen associated molecular pattern PAMP that bind their pathogen recognition receptors such as Toll- like receptors and directly triggering inflammation Biedermann 2006 Moreover S aureus PAMPs also influence T cell mediated skin inflammation by indirectly regulating skin homing of T cells and orchestrating chronic inflammation in AD skin Biedermann 2006 Biedermann et al 2006
Vitreoscilla filiformis Vf ATCC15551 used in this study is a non-photosynthetic non-fruiting gliding bacteria as defined according to the classification of Bergeys 1989 This filamentous bacterium belongs to the order of Beggiatoales It is a micro-organism found in sodic sulphuretted thermal springs recognized for their local anti-pruriginous and anti-inflammatory properties
The micro-organism Vitreoscilla filiformis Vf was cultivated on a defined and sterile medium expanded and isolated to constitute a biomass called pure extract of thermal plankton The term plankton describes the zooplankton chemiotrope microorganisms in contrast to the phytoplankton phototrope microorganisms At the end of culturing the biomass is concentrated by stabilized centrifugation and autoclaved
The technical preparation is a sterile aqueous suspension of the plankton In vitro studies show that this plankton supports the production of collagen by fibroblasts and reinforces the antioxidants systems it prevents Langerhans cell alterations reconstructed skin or organotypic skin culture exposed to UVB It exhibits non-specific immunomodulatory effects on cellular immunity and in particular on macrophages Patent US 6190671 B1 US 6242229 B1 WO-9402158
Preclinical studies showed that this extract has anti-inflammatory activities decreases ear oedema after acid arachidonic treatment and modulates contact hypersensitivity reaction with oxazolone Moreover this new compound promotes healing of epidermis and dermis scaring following suction blister or following incision in preclinical studies Patent US 6190671 B1 Therefore this new compound promises to alleviate infections usually found on the skin after skin burning protects skin against ultraviolet alterations and displayss moisturizing properties for the skin
Clinical trials showed that the bacterial extract Vitreoscilla filiformis is effective against acne and seborrhoeic dermatitis and promotes moisturization of the skin studies in Seoul Korea and in Nice France and patent FR-2283 223 and has been shown to be beneficial for sensitive skin clinical trial by Dr Desruelle F in Nice France Moreover a randomized double-blind placebo-controlled trial with a formulated 5 extract of Vitreoscilla filiformis on symmetric active lesions of AD according to a split-body design was performed with Prof J F Nicolas in Lyon France
In this study the treatment applied twice daily with the cream containing 5 Vitreoscilla filiformis extract was found to be safe and well tolerated Moreover this extract significantly alleviated AD in older children from 7 years old and adults compared with vehicle treatment p0008 Wilcoxon signed ranks test The therapeutic effects of the extract were observed within the second week of the application and steadily increased thereafter This effect of the cream containing 5 Vitreoscilla filiformis extract appeared to have a rapid onset especially in regard to pruritus as demonstrated using the mEASI index Paired testing confirmed a significant difference in the decrease of pruritus on the 5 Vitreoscilla filiformis extract treated side at day 28 p0046 Wilcoxon exact signed ranks test Gueniche et al 2006
Our task was to perform a double blind randomized prospective study comparing 5 Vitreoscilla filiformis extract cream B whith its vehicle cream A including measurements of biometric changes occurring during the use of the two creams
During the study biometrical and clinical measurements including the transepidermal water loss the qualification and quantification of skin microflora and the clinical evaluation of the skin findings before during and after the use of the creams was documented Further the probands experiences with the use of the creams were assessed Biometric variables of the skin are determined before during and after the use of cream A and cream B
The transepidermal water loss as biometrical value was estimated to assess the skin barrier function at all visits
We evaluated if topical application of cream A and cream B influenced the microflora of skin of atopic volunteers Qualification and quantification of several bacteria S aureus S epidermis P acnes Streptococci E coli was performed before during and at the end of the study period
In addition the intensity of pruritus and the clinical aspect of the skin was assessed
At the end of the study each volunteer filled out a questionnaire asking about oiliness distribution consistency and adsorption of the creams
Independently of the filaggrin study it was demonstrated earlier that a disrupted barrier function of the stratum corneum is present in atopics not only in involved skin but also in uninvolved dry skin facilitating permeation of various environmental substances into the skin Berardesca et al 1990 Werner et al 1985 Watanabe et al 1991 Loden et al 1992 As a biomarker an increased level of transepidermal water loss TEWL can be demonstrated Tagami et al 1985 Ghadially et al 1996 Various functional and morphological studies on atopic xerosis that clinically appeared without inflammation demonstrated that cellular inflammation is already present in atopic skin and a key and initial step in the development of atopic dermatitis Watanabe et al 1991 Uehara et al 1984 In fact barrier dysfunction atopic immune dysregulation and atopic dermatitis pathogenesis are not independent events but closely linked Biedermann 2006 Hudson 2006 Th2 lymphocytes dominate the atopic immune phenotype and are the underlying cell type responsible for the induction if IgE antibodies Biedermann et al 1999 2004 Barrier dysfunction predisposes for the development of Th2 lymphocytes and Th2 cells are the first cell type invading atopic skin initiating inflammation and the inflammatory vicious circle of inflammation Biedermann 2002 2004 Lametschwandtner et al 2004 Günther et al 2005 Next to Th2 lymphocytes in atopic dermatitis skin lesions infiltrates of eosinophils and cells of the mononuclear phagocyte lineage are found
The altered skin structure of people with atopic predisposition allows increased penetration of allergens and irritative substances Roll et al 2004 Hudson 2006 Many studies have shown that the extent of S aureus colonization correlates with AD disease activity Cho et al 2001 Biedermann 2006 In more than 90 of AD patients a massive skin colonization with S aureus up to 107cfucm2 of lesional skin can be found Matsui et al 2000 A prerequisite for bacterial colonisation are the genuine barrier dysfunction mechanical disruption of the barrier and trigger of inflammation scratching alkaline pH decreased IgA secretion through sweat production predominant Th2 cells inhibiting anti-infectious immune responses and reduced antimicrobial peptides all representing important pathophysiological features leading to the disruption of the primary skin defense system Biedermann et al 2001 BiedermannRöcken 2001 Biedermann et al 2002 Biedermann 2006 Howell 2005 Rieg 2005
Among several microbes colonising the skin the bacterium Staphylococcus aureus S aureus may play the most important role in the pathogenesis of dermatitis of atopic people Biedermann 2006 This colonization is observed not only in the involved inflammatory skin but also in the non involved dry skin The ratio Staphylococcus aureus Staphylococcus epidermidis is inverse in comparison to healthy skin Many studies have shown that the extent of S aureus colonization correlates with AD disease intensity Cho et al 2001
Reduced expression of antimicrobial peptides was demonstrated for AD skin and favours colonization with S aureus Ong et al N Engl J Med 2002 Howell et al Immunity 200624341-8 Rieg et al JI 2006 In addition dry skin may by itself allow colonization with bacteria such as S aureus Decreased levels of sphingosine which has antimicrobial properties and the fact that S aureus itself stimulates the hydrolysis of ceramides by bacterial derived ceramidase in atopic skin add the dysfunction of the immune barrier in AD Arikawa et al 2002 Kita et al 2002 The cell membrane of S aureus contains adhesins for epidermal and dermal laminin and fibronectin allowing attachemment of S aureus to the skin and these docking positions for S aureus are uncovered in lesional skin Cho et al 2001 The precise mechanism by which S aureus gains access to the dermis is unknown but it is suggested that again IL-4 produced by T helper type 2 cells induces fibronectin synthesis which in combination with plasma exsudation of fibrinogen allows S aureus to bind to the skin Moreover S aureus is able to encase itself in a kind of biofilm composed of a hydrated matrix of polysaccharides glycocalix and proteins which supports cell adhesion Akiyama et al 2003 After colonization S aureus contributes to skin inflammation eg by secreting toxins and an array of so called pathogen associated molecular pattern PAMP that bind their pathogen recognition receptors such as Toll- like receptors and directly triggering inflammation Biedermann 2006 Moreover S aureus PAMPs also influence T cell mediated skin inflammation by indirectly regulating skin homing of T cells and orchestrating chronic inflammation in AD skin Biedermann 2006 Biedermann et al 2006
Vitreoscilla filiformis Vf ATCC15551 used in this study is a non-photosynthetic non-fruiting gliding bacteria as defined according to the classification of Bergeys 1989 This filamentous bacterium belongs to the order of Beggiatoales It is a micro-organism found in sodic sulphuretted thermal springs recognized for their local anti-pruriginous and anti-inflammatory properties
The micro-organism Vitreoscilla filiformis Vf was cultivated on a defined and sterile medium expanded and isolated to constitute a biomass called pure extract of thermal plankton The term plankton describes the zooplankton chemiotrope microorganisms in contrast to the phytoplankton phototrope microorganisms At the end of culturing the biomass is concentrated by stabilized centrifugation and autoclaved
The technical preparation is a sterile aqueous suspension of the plankton In vitro studies show that this plankton supports the production of collagen by fibroblasts and reinforces the antioxidants systems it prevents Langerhans cell alterations reconstructed skin or organotypic skin culture exposed to UVB It exhibits non-specific immunomodulatory effects on cellular immunity and in particular on macrophages Patent US 6190671 B1 US 6242229 B1 WO-9402158
Preclinical studies showed that this extract has anti-inflammatory activities decreases ear oedema after acid arachidonic treatment and modulates contact hypersensitivity reaction with oxazolone Moreover this new compound promotes healing of epidermis and dermis scaring following suction blister or following incision in preclinical studies Patent US 6190671 B1 Therefore this new compound promises to alleviate infections usually found on the skin after skin burning protects skin against ultraviolet alterations and displayss moisturizing properties for the skin
Clinical trials showed that the bacterial extract Vitreoscilla filiformis is effective against acne and seborrhoeic dermatitis and promotes moisturization of the skin studies in Seoul Korea and in Nice France and patent FR-2283 223 and has been shown to be beneficial for sensitive skin clinical trial by Dr Desruelle F in Nice France Moreover a randomized double-blind placebo-controlled trial with a formulated 5 extract of Vitreoscilla filiformis on symmetric active lesions of AD according to a split-body design was performed with Prof J F Nicolas in Lyon France
In this study the treatment applied twice daily with the cream containing 5 Vitreoscilla filiformis extract was found to be safe and well tolerated Moreover this extract significantly alleviated AD in older children from 7 years old and adults compared with vehicle treatment p0008 Wilcoxon signed ranks test The therapeutic effects of the extract were observed within the second week of the application and steadily increased thereafter This effect of the cream containing 5 Vitreoscilla filiformis extract appeared to have a rapid onset especially in regard to pruritus as demonstrated using the mEASI index Paired testing confirmed a significant difference in the decrease of pruritus on the 5 Vitreoscilla filiformis extract treated side at day 28 p0046 Wilcoxon exact signed ranks test Gueniche et al 2006
Our task was to perform a double blind randomized prospective study comparing 5 Vitreoscilla filiformis extract cream B whith its vehicle cream A including measurements of biometric changes occurring during the use of the two creams
During the study biometrical and clinical measurements including the transepidermal water loss the qualification and quantification of skin microflora and the clinical evaluation of the skin findings before during and after the use of the creams was documented Further the probands experiences with the use of the creams were assessed Biometric variables of the skin are determined before during and after the use of cream A and cream B
The transepidermal water loss as biometrical value was estimated to assess the skin barrier function at all visits
We evaluated if topical application of cream A and cream B influenced the microflora of skin of atopic volunteers Qualification and quantification of several bacteria S aureus S epidermis P acnes Streptococci E coli was performed before during and at the end of the study period
In addition the intensity of pruritus and the clinical aspect of the skin was assessed
At the end of the study each volunteer filled out a questionnaire asking about oiliness distribution consistency and adsorption of the creams
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