Effect of Pimecrolimus Cream on Cathelicidin Levels in Subjects With Eczema

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT00946478
• Collaborator: Novartis (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 19
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effect of topical pimecrolimus on the immune system by assessing the levels of antimicrobial peptides in the skin of patients with eczema. It is hypothesized that pimecrolimus applied topically will repair the body's immune system in patients with eczema by increasing antimicrobial peptides.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: Pimecrolimus; Other: Vehicle cream	N/A

Detailed Description

Patients with atopic dermatitis (AD) have higher rates of skin infections from viruses and bacteria. They also have an impaired innate immune system. Antimicrobial peptides are a component of the innate immune system which are decreased in atopics. In vitro, pimecrolimus has demonstrated its ability to increase antimicrobial peptides. This study will examine the ability of pimecrolimus to increase antimicrobial peptides in vivo in AD patients. Thus, the study will yield a better understanding of the role of pimecrolimus in regulating the immune system in atopics.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Three-week, Double-blind, Randomized Study to Evaluate the Effect of Pimecrolimus Cream 1% on Cathelicidin Expression in the Skin of Subjects With Atopic Dermatitis
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pimecrolimus	Drug: Pimecrolimus; 20 AD patients will be given pimecrolimus 1% to apply twice daily for up to three weeks on each lesional site predetermined at baseline. Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).; Other Names: Elidel CASM 981
Sham Comparator: Vehicle cream	Other: Vehicle cream; 20 AD patients will be treated with vehicle cream twice daily for up to 3 weeks on each lesional site predetermined at baseline. Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).

Outcome Measures

Primary Outcome Measures

1. Cathelicidin mRNA Expression Levels in Adult Skin From Patients With AD [3 weeks]

   Delta-delta CT values were measured using RT-PCR of cathelicidin mRNA in human biopsy samples at baseline, and then 3 weeks after treatment with either pimecrolimus or placebo

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 18-70 years

2. Target lesion IGA ≥2

3. Target IGA=0 (for non-lesional site)

4. Male or female of any race and ethnicity

5. Chronic AD for more than one year duration

6. Subject of child-bearing potential must be willing to practice effective birth control during the study

7. Subject agrees to comply with study requirements and attend all required visits.

Exclusion Criteria:

1. Patients ≥ 18 years of age with only AD of the face

2. Women of childbearing potential not using the contraception method(s) specified in this study (abstinence, IUD, diaphragm, oral contraceptives)

3. Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study

4. Hypersensitivity to pimecrolimus cream or any excipient of the cream

5. Subject has a skin disorder in addition to dermatitis in the areas to be treated

6. Subject has Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier

7. Pregnant or nursing females

8. Immunocompromised patient (e.g., lymphoma, HIV/AIDS, Wiskott-Aldrich Syndrome), or with a history of active or malignant disease (excluding non-melanoma skin cancer)

9. History of psychiatric disease or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol

10. Patients known to be non-compliant with a medication regimen

11. Subjects with significant concurrent medical condition(s) at screening that in the view of the investigator prohibits participation in the study (e.g., severe concurrent allergic disease, condition associated with malignancy, and condition associated with immunosuppression)

12. Active viral or fungal skin infections at the target areas

13. Previous participation in this study

14. Ongoing participation in another investigational trial

15. Use of any oral or topical antibiotic during the study and up to one week prior to entering the study

16. Use of any local therapy for AD less than one week prior to screening

17. Use of any systemic immunosuppressive therapy for AD less than four weeks prior to screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego - Dept of Dermatology	La Jolla	California	United States	92037

Sponsors and Collaborators

• University of California, San Diego
• Novartis

Investigators

• Principal Investigator: Richard Gallo, MD, PhD, University of California, San Diego

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Richard Gallo, Chair, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00946478
• Other Study ID Numbers: UCSDMED
• First Posted: Jul 27, 2009
• Last Update Posted: Mar 10, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Richard Gallo, Chair, University of California, San Diego: atopic dermatitis; elidel; pimecrolimus; CASM981; immunity; cathelicidin; antimicrobial peptide; eczema
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema; Pimecrolimus

Study Results

Participant Flow

Arm/Group Title	Pimecrolimus	Vehicle Cream
Arm/Group Description	Pimecrolimus: 20 AD patients will be given pimecrolimus 1% to apply twice daily for up to three weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).	Vehicle cream: 20 AD patients will be treated with vehicle cream twice daily for up to 3 weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease9. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pimecrolimus	Vehicle Cream	Total
Arm/Group Description	Pimecrolimus: 20 AD patients will be given pimecrolimus 1% to apply twice daily for up to three weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).	Vehicle cream: 20 AD patients will be treated with vehicle cream twice daily for up to 3 weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease9. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.2 (8.4)	28.6 (9.5)	27.4 (9)
Sex/Gender, Customized (participants) [Number]
Male	9 45%	6 30%	15 37.5%
Female	7 35%	7 35%	14 35%
Unknown	4 20%	7 35%	11 27.5%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Cathelicidin mRNA Expression Levels in Adult Skin From Patients With AD
Description	Delta-delta CT values were measured using RT-PCR of cathelicidin mRNA in human biopsy samples at baseline, and then 3 weeks after treatment with either pimecrolimus or placebo
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pimecrolimus	Vehicle Cream
Arm/Group Description	Pimecrolimus: 20 AD patients will be given pimecrolimus 1% to apply twice daily for up to three weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).	Vehicle cream: 20 AD patients will be treated with vehicle cream twice daily for up to 3 weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease9. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).
Measure Participants	20	20
Mean (Standard Error) [delta-delta ct units on PCR]	.0016 (.002)	.0024 (.004)

Adverse Events

Arm/Group Title	Pimecrolimus		Vehicle Cream
Arm/Group Description	Pimecrolimus: 20 AD patients will be given pimecrolimus 1% to apply twice daily for up to three weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).		Vehicle cream: 20 AD patients will be treated with vehicle cream twice daily for up to 3 weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease9. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).
All Cause Mortality
	Pimecrolimus		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pimecrolimus		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Pimecrolimus		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.