Atopic dermatitis is a chronic relapsing disease with acute flares. The standard therapy is to treat acute flares using topical medications. The two most common classes of topical medications for atopic dermatitis are topical corticosteroids and topical calcineurin inhibitors.

Pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance.

The hypothesis of this trial is that the combination of the two agents will lead to faster clearance than the single agent of topical corticosteroids.

Condition	Intervention	Phase
Atopic Dermatitis	Drug: Combination of pimecrolimus and fluticasone	Phase IV

Further Study Details: 

Primary Outcomes: The primary efficacy variable will be change from baseline in the m-EASI (eczema area severity index) score.
Secondary Outcomes: · The time to clearance of the disease; (defined as the first day when m-EASI is scored by the investigator as 2 or less); · The percentage of target areas reaching a l-IGA or 0 or 1; · The percentage of target areas improved (i.e., decrease in l-IGA score from baseline); · The percentage of target areas reaching a m-EASI score of 2 or less; · Change from baseline in Patients’ Self Assessment of Disease Severity (PSA) of target areas
Expected Total Enrollment:  45

This trial is a double-blind controlled trial of fluticasone cream daily and pimecrolimus cream BID versus fluticasone cream daily and placebo cream BID for the treatment of acute flares of atopic dermatitis.

While pimecrolimus cream 1% has been proven to be effective in mild and moderate AD, there is a need for a fast control of severe skin lesions. On the other hand, reducing the duration of the topical corticosteroid treatment is a reasonable approach to minimize the occurrence of adverse effects.

Because pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance.

In vitro data have demonstrated that a combination of steroids and tacrolimus has synergistic effects on in vitro human lymphocyte proliferation. In addition, it has previously been reported, in a pilot investigation in two subjects, that a combination regimen of pimecrolimus 1% twice a day and fluticasone propionate cream 0.05% once daily was superior to fluticasone propionate cream 0.05% once daily in the acute treatment of AD.

This study is conducted to validate these findings in a larger number of patients.

Ages Eligible for Study:  2 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Age 2 to 65 years
• Clinical diagnosis of AD according to the AAD Consensus Conference (2001)
• At least two lesions of AD on symmetrical part of the body (same location for each side of the body), of severe intensity (m-EASI is at least 7 on each site, with erythema of at least 3 (severe) and papulation/infiltration of at least 3 (severe)) and similar severity (m-EASI does not differ from more than 2 points on both sides)
• Signed written informed consent
• Willingness and ability to comply with the study requirements
• Female is able to enter and participate in this study if she is of: · Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or · Childbearing potential, has a negative pregnancy test (urine) at the screen visit and agrees to an adequate method of birth control throughout the study (which may, at the investigator’s discretion, include abstinence)

Exclusion Criteria:

• History of immune deficiencies or history of malignant disease
• Patients with moderate to severe lichenification at the target areas (i.e. score 2 or 3)
• Active cutaneous bacterial, viral or fungal infections in target areas
• History of other skin disorders, including Netherton syndrome, that could interfere with the evaluations
• Use of any topical treatment known or suspected to have an effect on atopic dermatitis within one week prior to the screen visit (except for calcineurin inhibitors, for which the washout is 2 weeks)
• Use of any systemic treatment (including phototherapy) known or suspected to have an effect on AD within four weeks prior to the screen visit [(patients on a stable and low dose of inhaled steroids, on a stable dose of anti histamines, on stable dose of leukotriene antagonists, or receiving occasional short-acting b2-agonists for the treatment of asthma and topical corticosteroids (nasal spray) for the treatment of allergic rhinitis may participate). High-dose inhaled corticosteroids (> 440 mcg of fluticasone a day) and anti-IgE products are not permitted].
• Known sensitivity to pimecrolimus or vehicle (placebo) or fluticasone propionate cream or any of their ingredients
• Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
• Use of any other investigational agent in the last 30 days

Please refer to this study by ClinicalTrials.gov identifier  NCT00119158

Jonathan M Spergel, MD, PhD      215 590 6992    spergel@email.chop.edu
Kathy Pinzone, RN      215 590 9959    pinzone@email.chop.edu

Colorado
      National Jewish Research Medical Center, Denver,  Colorado,  80206,  United States; No longer recruiting
Illinois
      Northwestern University School of Medicine, Chicago,  Illinois,  60611,  United States; Recruiting
Texas
      University of Texas at Houston Medical School, Houston,  Texas,  77030,  United States; Recruiting

Study chairs or principal investigators

Jonathan M Spergel, MD, PhD,  Principal Investigator,  Children''''s Hospital of Philadelphia   

Study ID Numbers:  CHOP 2004-10-3975
Record last reviewed:  June 2005
Last Updated:  July 25, 2005
Record first received:  July 12, 2005
ClinicalTrials.gov Identifier:  NCT00119158
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-07-26