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Trial record 88 of 1210 for:    HISTAMINE

AMP-BPT and His-BPT for Assessment of Asthma (AMPHis)

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ClinicalTrials.gov Identifier: NCT02318043
Recruitment Status : Completed
First Posted : December 17, 2014
Last Update Posted : December 17, 2014
Sponsor:
Information provided by (Responsible Party):
Jinping Zheng, Guangzhou Institute of Respiratory Disease

Brief Summary:

Adenosine monophosphate (AMP) may reflect airway inflammation and hyperresponsiveness, but relationship between AMP and histamine (His, a conventional stimulus) bronchial provocation test (BPT) in asthma is not fully elucidated.

The investigators aimed to compare both BPTs and determine their usefulness in reflecting changes of asthmatic symptoms.

BPTs were performed in cross-over fashion, at 2-4day intervals. Cumulative doses eliciting 20% FEV1fall (PD20FEV1), diagnostic performance and adverse events were compared. Patients with PD20FEV1 lower than geometric mean were defined as responders, otherwise poor responders. Patients with uncontrolled and partly controlled asthma, who maintained their original inhaled corticosteroids therapy, underwent reassessment of airway responsiveness and asthmatic symptoms 3 and 6 months after.


Condition or disease Intervention/treatment Phase
Asthma Drug: inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg) Not Applicable

Detailed Description:

Airway hyperresponsiveness, the pivotal feature of asthma, can be assessed by bronchial provocation tests (BPTs), which may elicit bronchoconstriction via inhalation of stimuli. Histamine has been a direct stimulus for inducing bronchoconstriction via vasodilation, eosinophil chemotaxis and tissue edema. Clinically, histamine BPT (His-BPT) has gained extensive application for decades owing to the assay sensitivity and feasibility, but could not ideally predict anti-inflammatory treatment outcomes in practice. Additionally, mild adverse events (flushing and hoarseness) and insufficient capacity of identifying exercise-induced asthma have hampered further clinical applications.

Adenosine monophosphate (AMP) is an inflammatory mediator that serves as an indirect bronchial stimulus for detecting airway hyperresponsiveness in asthma. Compared with histamine, AMP may be pathophysiologically more relevant to airway inflammation and hyperresponsiveness and has been linked to presence and magnitude of atopy. However, differences of response to AMP-BPT and His-BPT in different asthma control levels and their associations with asthmatic symptom scores have not been fully elucidated.

We hypothesized that asthmatic patients, regardless of control levels, responded differentially to AMP-BPT and His-BPT, and that greater reduction in airway responsiveness to AMP (esp. responders of AMP-BPT) was associated with significant symptom alleviation. Henceforth, we sought to: 1) compare diagnostic performance and safety of AMP-BPT and His-BPT in different asthma control levels; 2) determine the association between airway responsiveness and asthmatic symptom scores.

Currently, His-BPT is recommended by the Chinese guideline and shares considerable similarity with methacholine (another conventional stimulus) BPT, we therefore did not perform the latter in this study.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Is Adenosine Monophosphate Superior to Histamine for Bronchial Provocation Test in Evaluation of Asthma?
Study Start Date : January 2007
Actual Primary Completion Date : December 2007
Actual Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Budesonide

Arm Intervention/treatment
Active Comparator: AMP-BPT
Methods of AMP-BPT, by applying dosimeters, resembled that reported previously [see references 21-25]. Briefly, dilutions were delivered via nebulizers (output: 160 μl/min) using automated APS pro system (JAEGER, Hochburg, Germany). Inhalation challenge with normal saline served as control step. Challenge steps were proceeded if FEV1 fall <15% and restored to <10% within 1 minute. Subsequent inhalation challenges were performed at 1-minute intervals, and ceased when FEV1 fell by ≥20%. Salbutamol was administered via spacer (Volumatic, Allen & Hanbury's, UK). Spirometry was reexamined at minutes 3, 5, 10 and thereafter, to ensure safety, before discharge.
Drug: inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)
Patients with uncontrolled and partly controlled asthma, following accomplishment of study 1, were invited to participate in observational study (study 2), which sought to determine usefulness of both BPTs in reflecting improvement of asthmatic symptoms following 3 and 6 months of moderate-dose ICSs treatment (400~800μg budesonide or equivalent). Patient continued to administer their original ICS during follow-up. During two follow-up visits (3 months apart), AMP-BPT, His-BPT and Hogg's symptom scores were reassessed.

Active Comparator: His-BPT
Methods of His-BPT, by applying dosimeters, resembled that reported previously [see references 21-25]. Briefly, dilutions were delivered via nebulizers (output: 160 μl/min) using automated APS pro system (JAEGER, Hochburg, Germany). Inhalation challenge with normal saline served as control step. Challenge steps were proceeded if FEV1 fall <15% and restored to <10% within 1 minute. Subsequent inhalation challenges were performed at 1-minute intervals, and ceased when FEV1 fell by ≥20%. Salbutamol was administered via spacer (Volumatic, Allen & Hanbury's, UK). Spirometry was reexamined at minutes 3, 5, 10 and thereafter, to ensure safety, before discharge.
Drug: inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)
Patients with uncontrolled and partly controlled asthma, following accomplishment of study 1, were invited to participate in observational study (study 2), which sought to determine usefulness of both BPTs in reflecting improvement of asthmatic symptoms following 3 and 6 months of moderate-dose ICSs treatment (400~800μg budesonide or equivalent). Patient continued to administer their original ICS during follow-up. During two follow-up visits (3 months apart), AMP-BPT, His-BPT and Hogg's symptom scores were reassessed.




Primary Outcome Measures :
  1. Cumulative dose eliciting 20% fall in FEV1 (PD20FEV1) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    Cumulative dose eliciting 20% fall in FEV1 (PD20FEV1), reported as

  2. Asthma symptom score as proposed by Hoggs et al [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    Asthma symptom score recorded within 1 week, with the highest possible score of 42 for the whole week


Secondary Outcome Measures :
  1. Baseline spirometry (FVC, FEV1, FEV1/FVC, MMEF, PEF) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    FVC, FEV1, FEV1/FVC, MMEF, PEF

  2. Maximal decrease in FVC following bronchial provocation (expressed as percentage) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    Maximal decrease in FVC following bronchial provocation, expressed as percentage as compared with baseline levels

  3. Maximal decrease in FEV1 following bronchial provocation (expressed as percentage) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    Maximal decrease in FEV1 following bronchial provocation, expressed as percentage as compared with baseline levels

  4. Maximal decrease in MMEF following bronchial provocation (expressed as percentage) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    Maximal decrease in MMEF following bronchial provocation, expressed as percentage as compared with baseline levels

  5. Maximal decrease in PEF following bronchial provocation (expressed as percentage) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    Maximal decrease in PEF following bronchial provocation, expressed as percentage as compared with baseline levels

  6. Assay positivity of AMP-BPT and His-BPT (expressed as percentage) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    Assay positivity of AMP-BPT and His-BPT, expressed as percentage

  7. Diagnostic performance of AMP-BPT and His-BPT (area under the receiver operation characteristic curve, sensitivity, specificity, Youden index) [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    area under the receiver operation characteristic curve, sensitivity, specificity, Youden index

  8. Changes in post-treatment asthma symptom scores [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    post-treatment minus pre-treatment asthma symptom score

  9. Changes in post-treatment PD20FEV1 [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    post-treatment minus pre-treatment PD20FEV1


Other Outcome Measures:
  1. incidence of adverse events of both BPTs [ Time Frame: up to 12 months (Jan 2007 to Dec 2007) ]
    adverse events of AMP-BPT and His-BPT



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. aged 18~65 years;
  2. nil respiratory infection within 3 weeks;
  3. normal chest radiography;
  4. baseline FEV1>60% predicted;
  5. withdrawn from, if any, oral leukotriene modifiers, corticosteroid or anti-histamine for 5 days, oral xanthenes or long-acting bronchodilators for 2 days, inhaled corticosteroids (ICSs) for 24 hours, and salbutamol for 6 hours

Exclusion Criteria:

  1. FEV1 fall ≥20% following saline inhalation;
  2. other chronic lower respiratory diseases (i.e. COPD);
  3. severe systemic diseases (i.e. uncontrolled hypertension, malignancy);
  4. limited understanding.

For healthy subjects, they had to be aged 18~65 years and had nil respiratory infection within 3 weeks, systemic diseases and had normal lung function.


Publications:
Ali S, Mustafa SJ, Driver AG, Metzger WJ. Release of adenosine in bronchoalveolar lavage fluid following allergen bronchial provocation in allergic rabbits. Am Rev Respir Dis 1991;143:A417
The Respiratory Society of the Chinese Medical Association. Guidelines for lung function testing (Part 3): Histamine and methacholine bronchial provocation test. Zhonghua Jie He He Hu Xi Za Zhi 2014; 37:566-71
O'Byrne P, Bateman ED, Bousquet JD. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Updated 2006. Available at http://www.ginasthma.org/Guidelines/guidelines-resources.html Latest accessed: Sep 20, 2014

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Responsible Party: Jinping Zheng, Professor, Guangzhou Institute of Respiratory Disease
ClinicalTrials.gov Identifier: NCT02318043     History of Changes
Other Study ID Numbers: GWJ
First Posted: December 17, 2014    Key Record Dates
Last Update Posted: December 17, 2014
Last Verified: December 2014
Keywords provided by Jinping Zheng, Guangzhou Institute of Respiratory Disease:
adenosine monophosphate
histamine
bronchial provocation test
asthma symptom score
asthma control
Additional relevant MeSH terms:
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Histamine
Histamine Agonists
Histamine Agents
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Budesonide
Adenosine
Salmeterol Xinafoate
Fluticasone-Salmeterol Drug Combination
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Adrenergic beta-2 Receptor Agonists