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Analysis of Response of Subjects With Atopic Dermatitis or Psoriasis to Oral Vitamin D3

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ClinicalTrials.gov Identifier: NCT00789880
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : January 22, 2013
Last Update Posted : April 12, 2017
Sponsor:
Collaborator:
Consortium of Food Allergy Research
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE November 11, 2008
First Posted Date  ICMJE November 13, 2008
Results First Submitted Date  ICMJE December 7, 2012
Results First Posted Date  ICMJE January 22, 2013
Last Update Posted Date April 12, 2017
Study Start Date  ICMJE December 2008
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2013)
  • Change From Baseline on Day 21 in Relative Abundance of CAMP mRNA in Lesional and Non-Lesional Skin for Atopic Dermatitis (AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Cathelicidin (CAMP) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. Cathelicidin amount is clinically significant as it is necessary to resist infection. Cathelicidin amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD.
  • Change From Baseline on Day 21 in Relative Abundance of CAMP mRNA in Non-Lesional Skin for Non-Atopic Dermatitis (Non-AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Cathelicidin (CAMP) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. Non-AD is defined as a healthy volunteer without atopic dermatitis, therefore the lesional skin-type was not measured in this group. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. Cathelicidin amount is clinically significant as it is necessary to resist infection. Cathelicidin amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD.
  • Change From Baseline on Day 21 in Relative Abundance of CAMP mRNA in Lesional and Non-Lesional Skin for Psoriatic Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Cathelicidin (CAMP) messenger ribonucleic acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline, Cathelicidin abundance in psoriasis has been hypothesized to correlate with increased inflammation. No direct clinical correlation is known.
  • Change From Baseline on Day 21 in Relative Abundance of HBD-3 mRNA in Lesional and Non-Lesional Skin for Atopic Dermatitis (AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Human Beta-defensin 3 (HBD-3) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies as measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. HBD-3 amount is clinically significant as it is necessary to resist infection. HBD-3 amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD.
  • Change From Baseline on Day 21 in Relative Abundance of HBD-3 mRNA in Non-Lesional Skin for Non-Atopic Dermatitis (Non-AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Human Beta-defensin 3 (HBD-3) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. Non-AD is defined as a healthy volunteer without atopic dermatitis, therefore the lesional skin-type was not measured in this group. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. HBD-3 amount is clinically significant as it is necessary to resist infection. HBD-3 amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD.
  • Change From Baseline on Day 21 in Relative Abundance of HBD-3 mRNA in Lesional and Non-Lesional Skin for Psoriatic Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Human Beta-defensin 3 (HBD-3) Messenger Ribonucleic acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. There is no known clinical correlation between HBD-3 and psoriasis.
Original Primary Outcome Measures  ICMJE
 (submitted: November 11, 2008)
Difference in change in expression of antimicrobial peptides (hCAP18/LL-37, HBD3) from baseline to study day 21 AD subjects' lesional and non-lesional skin biopsies. compared to change in expression of antimicrobial peptides from baseline to study day 21 [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
Change History Complete list of historical versions of study NCT00789880 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2013)
  • Change From Baseline on Day 21 in Relative Abundance of IL-13 mRNA in Lesional and Non-Lesional Skin for Atopic Dermatitis (AD) Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Cytokine interleukin-13 (IL-13) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. A decrease in IL-13 may be clinically correlated with improvement of AD.
  • Change From Baseline on Day 21 in Relative Abundance of IL-13 mRNA in Non-Lesional Skin for Non-Atopic Dermatitis (Non-AD) Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Cytokine interleukin-13 ( IL-13) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. Non-AD is defined as a healthy volunteer without atopic dermatitis. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. A decrease in IL-13 may be clinically correlated with improvement of AD.
  • Change From Baseline on Day 21 in Relative Abundance of IL-13 mRNA in Lesional and Non-Lesional Skin for Psoriatic Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo [ Time Frame: Baseline to Day 21 ]
    Cytokine interleukin-13 ( IL-13) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. There is no known clinical correlation between IL-13 and psoriasis.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2008)
  • Expression of antimicrobial peptides (hCAP18/LL-37, HBD3) at baseline and study day 21 in AD subjects' lesional and non-lesional skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
  • Expression of antimicrobial peptides (hCAP18/LL-37, HBD3) at baseline and study day 21 in non-AD subjects' skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
  • Change in expression of systemic antimicrobial peptides (hCAP18/LL-37, HBD3) from baseline to study day 21 in AD and non-AD subjects' saliva. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
  • Change in expression of TH2 cytokines IL-13 and IL-4 from baseline and study day 21 in AD subjects' lesional and non-lesional skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
  • Change in expression of TH2 cytokines IL-13 and IL-4 from baseline and study day 21 in non-AD subjects' skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
  • Change in expression of serum total IgE and RAST in AD and non-AD serum. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
  • Change in EASI score from baseline and study day 21 in AD subjects. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ]
  • The proportion of subjects in each arm who experience any Grade 3 or higher adverse events over the duration of follow-up in this trial. [ Time Frame: Throughout study and follow-up ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Analysis of Response of Subjects With Atopic Dermatitis or Psoriasis to Oral Vitamin D3
Official Title  ICMJE Analysis of the Response of Subjects With Atopic Dermatitis to Oral Vitamin D3 by Measurement of Antimicrobial Peptide Expression in Skin and Saliva
Brief Summary This study will examine whether administration of oral Vitamin D3 given over 21 days will change the antimicrobial peptide expression in the skin or saliva of subjects with Atopic Dermatitis (AD). This study will help researchers determine if the lack of the expression of antimicrobial peptides in individuals with AD plays a role in the susceptibility to eczema vaccinatum (EV).
Detailed Description

Atopic Dermatitis (AD) is a chronic inflammatory skin disorder in which the skin becomes extremely itchy and is susceptible to recurrent skin infections. AD is thought to occur from a combination of immunological, genetic, and environmental factors. Individuals with AD are at risk for developing a severe and widely disseminated infection called eczema vaccinatum (EV). EV is caused when the live attenuated vaccinia virus in the vaccine reproduces and spreads throughout the body. Individuals with AD lack certain antimicrobial peptides, specifically cathelicidins.

This trial also includes a sub-study with individuals who have psoriasis. Psoriasis is also an immune-mediated skin disease, and is characterized by scaling skin and inflammation (pain, swelling, heat, and redness). Most psoriasis cause patches of thick, red skin with silvery scales. These patches can itch or feel sore. This sub-study will provide additional information on psoriatic responses to oral vitamin D. (Originally listed separately as ADVN-CATH-03-01).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Atopic Dermatitis
  • Psoriasis
Intervention  ICMJE
  • Drug: Vitamin D3
    Administration of oral vitamin D3 at 4000IU
    Other Name: cholecalciferol
  • Drug: Placebo
    Administration of oral Vitamin D3 placebo
    Other Name: vitamin D3 placebo
Study Arms  ICMJE
  • Experimental: Vitamin D3
    Subjects received a 21-day course of oral vitamin D3 (cholecalciferol, 4,000 international units [IU]
    Intervention: Drug: Vitamin D3
  • Placebo Comparator: Placebo
    Subjects received a 21-day course of oral vitamin D3-placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 18, 2013)
82
Original Estimated Enrollment  ICMJE
 (submitted: November 11, 2008)
60
Actual Study Completion Date  ICMJE December 2009
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria (Main Study):

  • Definitive diagnosis of AD for at least 6 months, stringently diagnosed using the ADVN Standard Diagnostic Criteria, and has lesional skin present OR is a non-atopic healthy control subject with no personal or family history of food allergy, AD, asthma, or allergic rhinitis
  • Residing in the US.

Inclusion Criteria (Sub-Study):

  • Definitive diagnosis of typical plaque psoriasis for at least 6 months, stringently diagnosed using the ADVN Standard Diagnostic Criteria; or is an AD or non-atopic healthy control subject participating in the main protocol ADVN CATH 03.
  • Residing in the US.

Exclusion Criteria (Main Study):

  • Presence of atopy without stringent AD features, allowing only a presumptive diagnosis of AD
  • Presence of AD with exfoliative erythroderma
  • Presence of psoriasis
  • Pregnant or lactating females
  • Existence of ongoing dental disease (e.g., gingivitis)
  • History of bleeding disorders
  • Presence of severe AD that would be exacerbated by withholding of topical corticosteroids, oral or topical antibiotics, topical or systemic antihistamines, oral antivirals, immune enhancers (e.g., imiquimod), or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and throughout the course of the trial
  • Receiving systemic immunosuppressives, chemotherapeutic agents, anti-inflammatory biologics (e.g., alefacept, etanercept), systemic, oral, injectable or inhaled steroids, vitamin D supplements (more than 400 IU daily) or oral calcineurin inhibitors 30 days prior to the Study Visit 2 (Baseline) or anytime during the course of the trial
  • Using topical corticosteroids, oral or topical antibiotics, oral antivirals, immune enhancers (e.g., imiquimod), topical or systemic antihistamines, or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and during the course of the trial
  • Receiving phototherapy (e.g., UVB, psoralen plus ultraviolet light A [PUVA]) within 30 days of Study Visit 2 (Baseline) and during the course of the trial
  • Having autoimmune or immunodeficiency disease
  • Presence of active systemic fungal (excluding nail fungus), bacterial, or viral infections
  • History of or presence of active systemic malignancy, excluding uncomplicated non-melanoma skin cancer
  • Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
  • Inability or unwillingness of a participant to give written informed consent
  • Diabetes
  • Certain screening laboratory values not within normal limits, which would include calcium, serum PTH, and serum creatinine
  • History of kidney disease or kidney stones
  • Currently taking barbiturates such as phenobarbital (Luminal)
  • Currently taking carbamazine (Tegretol), digoxin, phenytoin (Dilantin) or fosphenytoin (cerebyx)
  • Currently taking diuretics such as thiazide diuretics, calcium channel blockers, or beta-blockers
  • Currently taking magnesium-containing antacids, mineral oil, cholestyramine (Questran), colestipol(Colestid), orlistat (xenical), the fat substitute Olestra, cod liver oil, fish oil, or omega 3 fatty acids
  • Currently taking oral antifungals such as ketoconazole
  • History of serious or life-threatening anaphylactic reaction to tape or adhesives
  • Lidocaine allergy
  • History of or active hyperparathyroidism, sarcoid, tuberculosis or lymphoma.

Exclusion Criteria (Sub-Study):

  • Presence of AD with exfoliative erythroderma
  • Presence of psoriasis with exfoliative erythroderma or presence of guttate psoriasis, primary palmoplantar psoriasis, or pustular psoriasis
  • Pregnant or lactating females
  • Existence of ongoing dental disease (e.g., gingivitis)
  • History of bleeding disorders
  • Presence of psoriasis that would be severely exacerbated by withholding topical corticosteroids, oral or topical antibiotics, topical or systemic antihistamines, oral antivirals, immune enhancers (e.g.,imiquimod), or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and throughout the course of the trial
  • Receiving systemic immunosuppressives, chemotherapeutic agents, anti-inflammatory biologics (e.g., alefacept, etanercept), systemic, oral, injectable, or inhaled steroids, vitamin D supplements (more than 400 IU daily), or oral calcineurin inhibitors, 30 days prior to the Study Visit 2 (Baseline) or anytime during the course of the trial
  • Using topical corticosteroids, oral or topical antibiotics, oral antivirals, immune enhancers (e.g., imiquimod), topical or systemic antihistamines, or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and during the course of the trial
  • Receiving phototherapy (e.g., UVB, psoralen plus ultraviolet light A [PUVA]) within 30 days of Study Visit 2 (Baseline) and during the course of the trial
  • Having autoimmune or immunodeficiency disease
  • Presence of active systemic fungal (excluding nail fungus), bacterial, or viral infections
  • History of or presence of active systemic malignancy, excluding uncomplicated non-melanoma skin cancer
  • Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
  • Inability or unwillingness of a participant to give written informed consent
  • Diabetes
  • Screening laboratory values not within normal limits, which would include calcium, serum PTH, and serum creatinine
  • History of kidney disease or kidney stones
  • Currently taking barbiturates such as phenobarbital (Luminal)
  • Currently taking carbamazepine (Tegretol), digoxin, phenytoin (Dilantin) or fosphenytoin (cerebyx)
  • Currently taking diuretics such as thiazide diuretics, calcium channel blockers, or beta-blockers
  • Currently taking magnesium-containing antacids, mineral oil, cholestyramine (Questran), colestipol (Colestid), orlistat (xenical), the fat substitute Olestra, cod liver oil, fish oil, or omega 3 fatty acids
  • Currently taking oral antifungals such as ketoconazole
  • History of serious or life-threatening anaphylactic reaction to tape or adhesives
  • Lidocaine allergy
  • History of or active hyperparathyroidism, sarcoid, tuberculosis or lymphoma.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00789880
Other Study ID Numbers  ICMJE DAIT ADVN CATH 03
DAIT-ADVN-CATH-03-01 Sub-study ( Other Identifier: DAIT, NIAID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Consortium of Food Allergy Research
Investigators  ICMJE
Study Chair: Richard Gallo, MD, PhD University of California, San Diego
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP