Back to resultsA Study on the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics (MK-0000-175)
Primary Purpose
Asthma
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Prednisone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring Nasal Allergen Challenge, Inhaled Allergen Challenge, Asthma
Eligibility Criteria
Inclusion Criteria:
- Has a clinical history of mild to moderate asthma for at least 6 months, but otherwise is in good health
- Participant with allergic rhinitis and asthma has a history of nonseasonal airway symptoms in response to aeroallergens OR has seasonal symptoms but can be evaluated out-of-season
- Is clinically stable and free of respiratory infection or change in allergen exposure for at least 4 weeks prior to start of study
Exclusion Criteria:
- Has intolerance to the study drug, inhaled salbutamol, antihistamines, or any other potential asthma/anaphylaxis rescue medication
- Has intolerance to lidocaine/lignocaine, sedatives, atropine or glycopyrrolate, or any other medication associated with bronchoscopy
- Has taken oral parenteral corticosteroids within 8 weeks or inhaled corticosteroids/nasal corticosteroids within 5 weeks of screening and/or during the study
- Has recent (4 weeks) or ongoing upper or lower respiratory tract infection
- Has active allergic rhinitis at screening
- Has received a vaccination within 3 weeks of screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Prednisone, then Placebo
Placebo, then Prednisone
Arm Description
Prednisone in the first crossover treatment period and placebo in the second crossover treatment period
Placebo in the first crossover treatment period and prednisone in the second crossover treatment period
Outcomes
Primary Outcome Measures
Geometric Mean Fold Change From Baseline in Interleukin-5 (IL-5) Concentration From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, nasal exudates (NE) and sputum (SP) were collected, then the concentrations of IL-5 were determined from NE and SP collected after 7 hours and previously at baseline (BL), to derive the fold change (FC) from BL for each participant. The geometric mean (GM) was determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Interleukin-13 (IL-13) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-13 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Secondary Outcome Measures
Geometric Mean Fold Change From Baseline in Thymus and Activation Regulated Chemokine (TARC) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of TARC were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Eotaxin-3 From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of Eotaxin-3 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Change in Vibration Response Imaging (VRI) After Metacholine Exposure
One hour before treatment with prednisone/placebo, participants inhaled for 2 minutes a nebulised solution of metacholine (0.13 ml/min); then one hour after prednisone/placebo treatment were challenged with allergens. From 1 to 7 hours after allergen challenge, ventilatory heterogeneity was assessed by Vibration Response Imaging (VRI) by monitoring the following: inspiration/expiration (I/E) amplitude ratio, I/E duration ratio, synchrony duration, and quantitative lung data.
Geometric Mean Fold Change From Baseline in RNA Expression for Genes Encoding IL-5 and IL-13 From Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, SP were collected, then the RNA expression profiles of IL-5 and IL-13 genes were determined from SP collected after 7 hours and previously at baseline, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Interleukin-17 (IL-17) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-17 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Interleukin-1β (IL-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-1β were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Macrophage Inflammatory Protein-1β (MIP-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of MIP-1β were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Thymic Stromal Lymphopoietin (TSLP) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of TSLP were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Interleukin-23 (IL-23) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-23 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was plan to be determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Cytokines From Bronchoalveolar Lavage Fluid (BALf)
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 23 hours had elapsed, BALf were collected, then the concentrations of IL-5, IL-13, and TARC were determined from BALf collected after 23 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.
Geometric Mean Fold Change From Baseline in Nasal and Bronchial Eicosanoids and Leukotrienes at 7 Hours Post-allergen Challenge.
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then prostaglandin and leukotriene concentrations were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.
Full Information
NCT ID
NCT01193049
First Posted
August 30, 2010
Last Updated
September 3, 2015
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01193049
Brief Title
A Study on the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics (MK-0000-175)
Official Title
A Two-Part, Randomized Clinical Trial to Study the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the relationship between upper and lower airway allergen-induced cytokine responses in mild asthmatics by attempting to demonstrate the following: 1) a positive correlation between allergen-induced Type 2 T-helper cell (Th2) cytokines (interleukins 5 and 13) in sputum and nasal exudates; and 2) a positive correlation between effects of prednisone versus placebo on Th2 cytokines in sputum and nasal exudates.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Nasal Allergen Challenge, Inhaled Allergen Challenge, Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prednisone, then Placebo
Arm Type
Experimental
Arm Description
Prednisone in the first crossover treatment period and placebo in the second crossover treatment period
Arm Title
Placebo, then Prednisone
Arm Type
Experimental
Arm Description
Placebo in the first crossover treatment period and prednisone in the second crossover treatment period
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone (25 mg) tablets as a single oral dose on Day 1 of each study period
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo tablets as a single oral dose on Day 1 of each study period
Primary Outcome Measure Information:
Title
Geometric Mean Fold Change From Baseline in Interleukin-5 (IL-5) Concentration From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, nasal exudates (NE) and sputum (SP) were collected, then the concentrations of IL-5 were determined from NE and SP collected after 7 hours and previously at baseline (BL), to derive the fold change (FC) from BL for each participant. The geometric mean (GM) was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Interleukin-13 (IL-13) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-13 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Secondary Outcome Measure Information:
Title
Geometric Mean Fold Change From Baseline in Thymus and Activation Regulated Chemokine (TARC) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of TARC were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Eotaxin-3 From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of Eotaxin-3 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Change in Vibration Response Imaging (VRI) After Metacholine Exposure
Description
One hour before treatment with prednisone/placebo, participants inhaled for 2 minutes a nebulised solution of metacholine (0.13 ml/min); then one hour after prednisone/placebo treatment were challenged with allergens. From 1 to 7 hours after allergen challenge, ventilatory heterogeneity was assessed by Vibration Response Imaging (VRI) by monitoring the following: inspiration/expiration (I/E) amplitude ratio, I/E duration ratio, synchrony duration, and quantitative lung data.
Time Frame
From 1 to 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in RNA Expression for Genes Encoding IL-5 and IL-13 From Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, SP were collected, then the RNA expression profiles of IL-5 and IL-13 genes were determined from SP collected after 7 hours and previously at baseline, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Interleukin-17 (IL-17) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-17 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Interleukin-1β (IL-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-1β were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Macrophage Inflammatory Protein-1β (MIP-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of MIP-1β were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Thymic Stromal Lymphopoietin (TSLP) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of TSLP were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Interleukin-23 (IL-23) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-23 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was plan to be determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Cytokines From Bronchoalveolar Lavage Fluid (BALf)
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 23 hours had elapsed, BALf were collected, then the concentrations of IL-5, IL-13, and TARC were determined from BALf collected after 23 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 23 hours post-allergen challenge
Title
Geometric Mean Fold Change From Baseline in Nasal and Bronchial Eicosanoids and Leukotrienes at 7 Hours Post-allergen Challenge.
Description
Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then prostaglandin and leukotriene concentrations were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.
Time Frame
Baseline and 7 hours post-allergen challenge
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:
Has a clinical history of mild to moderate asthma for at least 6 months, but otherwise is in good health
Participant with allergic rhinitis and asthma has a history of nonseasonal airway symptoms in response to aeroallergens OR has seasonal symptoms but can be evaluated out-of-season
Is clinically stable and free of respiratory infection or change in allergen exposure for at least 4 weeks prior to start of study
Exclusion Criteria:
Has intolerance to the study drug, inhaled salbutamol, antihistamines, or any other potential asthma/anaphylaxis rescue medication
Has intolerance to lidocaine/lignocaine, sedatives, atropine or glycopyrrolate, or any other medication associated with bronchoscopy
Has taken oral parenteral corticosteroids within 8 weeks or inhaled corticosteroids/nasal corticosteroids within 5 weeks of screening and/or during the study
Has recent (4 weeks) or ongoing upper or lower respiratory tract infection
Has active allergic rhinitis at screening
Has received a vaccination within 3 weeks of screening
12. IPD Sharing Statement
Learn more about this trial
A Study on the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics (MK-0000-175)
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