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Assessing the Impact of Pioglitazone on Skin Barrier Function in Atopic Dermatitis Patients

Primary Purpose

Atopic Dermatitis

Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pioglitazone
Placebo (for pioglitazone)
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atopic Dermatitis focused on measuring atopic dermatitis, eczema

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • i. Moderate to Severe AD: EASI ≥ 10 ii. Active Atopic Dermatitis: Subjects must have within the last 3 months according to medical records or by medical exam of the investigator:

    • Pruritus
    • Eczema (acute, subacute, chronic)

I. Typical morphology and age-specific patterns - Patterns include (1) facial, neck, and extensor involvement in infants and children, (2) current or prior flexural lesions in any age group, (3) sparing groin and axillary regions.

II. Chronic or relapsing history

iii. Extrinsic they must also meet both of the following: serum total IgE ≥ 1.5 S.D. greater than the age-matched norms and positive multi-allergen RAST (Phadiatop).

Additionally, subjects must have TEWL of nonlesional skin of upper arm that is ≥ 8 gm/m2/h at screening visit. This is to ensure that we are in fact studying the subset of AD subjects who have a skin barrier defect.

Exclusion Criteria:

  • Unwillingness or inability to complete the Informed Consent process
  • Subjects with a history of keloid formation
  • History of lidocaine or Novocain allergy
  • Subjects with a systemic infection requiring a course of systemic antibiotics or antivirals within the last 2 weeks
  • Subjects with MD diagnosed Type 1 or 2 diabetes mellitus
  • Subjects with NYHA class III or IV cardiac status
  • Subjects with a history of liver disease (EtOH, viral hepatitis, drug-induced hepatitis or other)
  • Subjects with evidence of an underlying systemic disease based on history and physical (other than the above diagnostic categories (and associated allergic disorders), or well-controlled hypertension, or hyperlipidemia).
  • History of cancer other than nonmelanomatous skin cancer or cervical dysplasia
  • Participants enrolled while on a systemic treatment for their atopic dermatitis (e.g. cyclosporine, mycophenolate mofetil) must remain on a stable dose for the duration of the study

Sites / Locations

  • University of Rochester Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Pioglitazone

Arm Description

Subjects randomized to placebo will receive opaque size "00" gelatin capsules containing 240mg lactose. As with the intervention group, 1 capsule will be taken by each day throughout the treatment period.

Subjects randomized to pioglitazone will receive opaque size "00" gelatin capsules containing pioglitazone. For the first 3 weeks, capsules will contain 30 mg pioglitazone. For the remaining 9 weeks of the treatment period, capsules will contain 45 mg pioglitazone unless subjects are unable to tolerate this increased dose. One capsule will be taken by each day throughout the treatment period.

Outcomes

Primary Outcome Measures

Noninvasive barrier measurements (TEWL)
Transepidermal Water Loss (TEWL) will be measured at multiple time points throughout the study as a surrogate for skin barrier integrity.
Transepithelial electrical resistance (TEER) and permeability
Skin biopsies will be performed twice during the study. The integrity of the skin barrier will be assessed in the lab by transepithelial electrical resistance (TEER) and permeability of the biopsy specimens.
mRNA
Ex vivo assessment of mRNA expression of key epidermal barrier proteins will also be performed on the biopsy specimens.

Secondary Outcome Measures

Skin Irritancy
The clinical efficacy of PIO will be assessed by quantifying the skin response to a model irritant, sodium lauryl sulphate (SLS) at several time points. Subjects will be exposed for 24 h on the dominant inner arm to SLS at three concentrations (wt/vol in water - 0.125, 0.5 and 2%) (Fluka) using standard patch test reagents (Finn chambers of 18-mm diam, Filter Discs & Scanpor tape). Before application and at several time points after removal, TEWL and erythema will be measured at the exposed site and at a control site. Erythema will be measured using a colorimeter (Minolta CR-200).

Full Information

First Posted
September 26, 2012
Last Updated
December 1, 2014
Sponsor
University of Rochester
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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1. Study Identification

Unique Protocol Identification Number
NCT01695707
Brief Title
Assessing the Impact of Pioglitazone on Skin Barrier Function in Atopic Dermatitis Patients
Official Title
Assessing the Impact of Pioglitazone on Skin Barrier Function in Atopic Dermatitis Patients
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Withdrawn
Why Stopped
Insufficient Funding.
Study Start Date
March 2013 (undefined)
Primary Completion Date
January 2014 (Anticipated)
Study Completion Date
June 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Many patients with eczema (atopic dermatitis) have an inherent defect in their skin barrier as demonstrated by high water loss. In laboratory conditions, studies have shown that pioglitazone restores the skin barrier function in skin from eczema patients. The purpose of this study is to determine if taking pioglitazone improves the skin barrier function in people with eczema.
Detailed Description
Enrolled patients will be randomized to either placebo or pioglitazone. Each randomized subject will have a skin biopsy and skin irritancy assay performed prior to treatment and at the end of 12 weeks of treatment. Noninvasive barrier measurements including transepidermal water loss will be recorded at all study visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
Keywords
atopic dermatitis, eczema

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to placebo will receive opaque size "00" gelatin capsules containing 240mg lactose. As with the intervention group, 1 capsule will be taken by each day throughout the treatment period.
Arm Title
Pioglitazone
Arm Type
Experimental
Arm Description
Subjects randomized to pioglitazone will receive opaque size "00" gelatin capsules containing pioglitazone. For the first 3 weeks, capsules will contain 30 mg pioglitazone. For the remaining 9 weeks of the treatment period, capsules will contain 45 mg pioglitazone unless subjects are unable to tolerate this increased dose. One capsule will be taken by each day throughout the treatment period.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
see Arm Description
Intervention Type
Drug
Intervention Name(s)
Placebo (for pioglitazone)
Intervention Description
see Arm Description
Primary Outcome Measure Information:
Title
Noninvasive barrier measurements (TEWL)
Description
Transepidermal Water Loss (TEWL) will be measured at multiple time points throughout the study as a surrogate for skin barrier integrity.
Title
Transepithelial electrical resistance (TEER) and permeability
Description
Skin biopsies will be performed twice during the study. The integrity of the skin barrier will be assessed in the lab by transepithelial electrical resistance (TEER) and permeability of the biopsy specimens.
Title
mRNA
Description
Ex vivo assessment of mRNA expression of key epidermal barrier proteins will also be performed on the biopsy specimens.
Secondary Outcome Measure Information:
Title
Skin Irritancy
Description
The clinical efficacy of PIO will be assessed by quantifying the skin response to a model irritant, sodium lauryl sulphate (SLS) at several time points. Subjects will be exposed for 24 h on the dominant inner arm to SLS at three concentrations (wt/vol in water - 0.125, 0.5 and 2%) (Fluka) using standard patch test reagents (Finn chambers of 18-mm diam, Filter Discs & Scanpor tape). Before application and at several time points after removal, TEWL and erythema will be measured at the exposed site and at a control site. Erythema will be measured using a colorimeter (Minolta CR-200).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: i. Moderate to Severe AD: EASI ≥ 10 ii. Active Atopic Dermatitis: Subjects must have within the last 3 months according to medical records or by medical exam of the investigator: Pruritus Eczema (acute, subacute, chronic) I. Typical morphology and age-specific patterns - Patterns include (1) facial, neck, and extensor involvement in infants and children, (2) current or prior flexural lesions in any age group, (3) sparing groin and axillary regions. II. Chronic or relapsing history iii. Extrinsic they must also meet both of the following: serum total IgE ≥ 1.5 S.D. greater than the age-matched norms and positive multi-allergen RAST (Phadiatop). Additionally, subjects must have TEWL of nonlesional skin of upper arm that is ≥ 8 gm/m2/h at screening visit. This is to ensure that we are in fact studying the subset of AD subjects who have a skin barrier defect. Exclusion Criteria: Unwillingness or inability to complete the Informed Consent process Subjects with a history of keloid formation History of lidocaine or Novocain allergy Subjects with a systemic infection requiring a course of systemic antibiotics or antivirals within the last 2 weeks Subjects with MD diagnosed Type 1 or 2 diabetes mellitus Subjects with NYHA class III or IV cardiac status Subjects with a history of liver disease (EtOH, viral hepatitis, drug-induced hepatitis or other) Subjects with evidence of an underlying systemic disease based on history and physical (other than the above diagnostic categories (and associated allergic disorders), or well-controlled hypertension, or hyperlipidemia). History of cancer other than nonmelanomatous skin cancer or cervical dysplasia Participants enrolled while on a systemic treatment for their atopic dermatitis (e.g. cyclosporine, mycophenolate mofetil) must remain on a stable dose for the duration of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa A Beck, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States

12. IPD Sharing Statement

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Assessing the Impact of Pioglitazone on Skin Barrier Function in Atopic Dermatitis Patients

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