A Study on the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics (MK-0000-175)

A Two-Part, Randomized Clinical Trial to Study the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Prednisone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisone, then Placebo; Prednisone in the first crossover treatment period and placebo in the second crossover treatment period	Drug: Prednisone; Prednisone (25 mg) tablets as a single oral dose on Day 1 of each study period; Drug: Placebo; Matching placebo tablets as a single oral dose on Day 1 of each study period
Experimental: Placebo, then Prednisone; Placebo in the first crossover treatment period and prednisone in the second crossover treatment period	Drug: Prednisone; Prednisone (25 mg) tablets as a single oral dose on Day 1 of each study period; Drug: Placebo; Matching placebo tablets as a single oral dose on Day 1 of each study period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge
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.	From 1 to 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge
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.	Baseline and 23 hours post-allergen challenge
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.	Baseline and 7 hours post-allergen challenge

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: August 30, 2010
• First Posted (Estimate): September 1, 2010

Study Record Updates

• Last Update Posted (Estimate): September 4, 2015
• Last Update Submitted That Met QC Criteria: September 3, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Nasal Allergen Challenge, Inhaled Allergen Challenge, Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 0000-175; 2010-020518-27 (EudraCT Number: From the European Union Drug Regulatory Authorities Clinical Trial System)