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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01193049
First received: August 30, 2010
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Prednisone
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: From 1 to 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and 23 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline and 7 hours post-allergen challenge ] [ Designated as safety issue: No ]
    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.


Enrollment: 11
Study Start Date: August 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01193049     History of Changes
Other Study ID Numbers: 0000-175, 2010-020518-27
Study First Received: August 30, 2010
Results First Received: June 27, 2012
Last Updated: August 30, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Merck Sharp & Dohme Corp.:
Nasal Allergen Challenge, Inhaled Allergen Challenge, Asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Prednisone
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 24, 2014