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

This study has been withdrawn prior to enrollment.
(Insufficient Funding.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Rochester
ClinicalTrials.gov Identifier:
NCT01695707
First received: September 26, 2012
Last updated: November 8, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention
Atopic Dermatitis
Drug: Pioglitazone
Drug: Placebo (for pioglitazone)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Assessing the Impact of Pioglitazone on Skin Barrier Function in Atopic Dermatitis Patients

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Noninvasive barrier measurements (TEWL) [ Designated as safety issue: No ]
    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 [ Designated as safety issue: No ]
    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 [ Designated as safety issue: No ]
    Ex vivo assessment of mRNA expression of key epidermal barrier proteins will also be performed on the biopsy specimens.


Secondary Outcome Measures:
  • Skin Irritancy [ Designated as safety issue: No ]
    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).


Enrollment: 0
Study Start Date: March 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
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.
Drug: Placebo (for pioglitazone)
see Arm Description
Experimental: Pioglitazone

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.

Drug: Pioglitazone
see Arm Description
Other Name: Actos

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01695707

Locations
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Lisa A Beck, MD University of Rochester
  More Information

No publications provided

Responsible Party: University of Rochester
ClinicalTrials.gov Identifier: NCT01695707     History of Changes
Other Study ID Numbers: RSRB00041078, 1R21AR062357
Study First Received: September 26, 2012
Last Updated: November 8, 2013
Health Authority: KAI Research has appointed an independent safety officer, Gil Yosipovitch, MD to oversee this trial.

Keywords provided by University of Rochester:
atopic dermatitis
eczema

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014