Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma

Asthma Clinical Trial

Official title:

Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02703467
• Other study ID #: 13/LO/1453
• Status: Completed
• Start date: August 1, 2015
• Est. completion date: June 30, 2016

Study information

• Verified date: October 2019
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study will be to determine whether there is any role for measuring Hydrogen Sulphide (H2S) in the exhaled breath in terms of management of the patient with asthma.

The investigators will recruit patients with a range of severity of asthma and health volunteers. Levels of Hydrogen Sulphide will be measured in exhaled breath and blood. Also exhaled Nitric Oxide, Spirometry and asthma symptom scores will be measured at each study visit. Participants will attend either 2 or 4 separate visits.

The investigators will determine whether there is a relationship between exhaled Hydrogen Sulphide and asthma severity.

Description:

Objectives:

1. Perform a cross-sectional study in non-asthmatic subjects and asthmatic subjects of varying severities of the levels of Hydrogen Sulphide in exhaled breath in relation to the severity and control of asthma

2. Compare the levels of exhaled Hydrogen Sulphide with exhaled Nitric Oxide.

We will recruit 30 health volunteers and 90 patients with a range of severity of asthma.

Particpants will attend for either 2 or 4 visits. At these visits the following measurements will be taken:

1. Exhaled Hydrogen Sulphide

2. Serum Hydrogen Sulphide

2. Exhaled Nitric Oxide 3. Spirometry 4. Asthma Symptom Score (ACQ)

The investigators will use a Hydrogen Sulphide UV fluorescent machine Model T101 (0-50 ppb to 0-20 ppm) (Cal-Bay Control Inc, USA) to measure directly on line exhaled breath Hydrogen Sulphide. This method has been used previously in normal people, but we will first determine whether there is an exhaled flow-dependence on the measurement of H2S levels. The investigators will use a hand-held Nitric Oxide machine (NO Breath) to measure Nitric Oxide in exhaled breath.

Subjects must have asthma according to one or more of the following criteria documented in the last 12 months:

1. Improvement in FEV1 (forced expiratory volume at one second) ≥ 12% and 200ml predicted after inhalation of 400 mcg salbutamol

2. Airway hyper-responsiveness (PC20 <8mg/ml)

3. Diurnal variation in PEF (peak expiratory flow): amplitude % mean of twice daily PEF > 8%

4. Decrease in pre-bronchodilator FEV1 >12% and >200mls within 4 weeks after tapering treatment with one or more of the following drugs: inhaled corticosteroids, oral corticosteroids, long-acting beta-agonists, long-acting beta-agonists and short-acting beta-agonists.

PLUS A history of wheeze occurring spontaneously or on exertion

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: June 30, 2016
• Est. primary completion date: June 30, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

All patients must be able to give informed consent. The definition of the severity of their asthma will be according to the GINA (Global Initiative for Asthma) guidelines dependent on the amount of therapy needed to control asthma. The investigators will also include at least 45 patients with severe asthma defined on the basis of: Uncontrolled asthma: three or more of the following features present in any week in the previous 4 weeks:

• Daytime symptoms more than twice per week

• Any limitation of activities

• Nocturnal symptoms once or more per week

• Need for reliever treatment more than twice per week

• Pre bronchodilator FEV1 <80% predicted or personal best OR

• Frequent severe exacerbations (=2 per year) OR

• Require prescription of daily or alternate day oral corticosteroids (OCS) to achieve asthma control despite the prescription of high dose inhaled corticosteroids (>1000mcg fluticasone propionate daily or equivalent) or maintenance oral corticosteroids plus a long acting beta agonist or one other controller medication (for example anti-cholinergics, leukotriene receptor antagonists or theophylline).

Diagnosis of asthma for the asthma cohort: Subjects must have asthma according to one or more of the following criteria documented in the last 12 months

• improvement in FEV1 = 12% and 200ml predicted after inhalation of 400 mcg salbutamol

• airway hyper-responsiveness (PC20 <8mg/ml)

• diurnal variation in PEF: amplitude % mean of twice daily PEF > 8%

• decrease in pre bronchodilator FEV1 >12% and >200mls within 4 weeks after tapering treatment with one or more of the following drugs: inhaled corticosteroids, oral corticosteroids, long-acting beta-agonists, long-acting beta-agonists and short-acting beta-agonists.

PLUS a history of wheeze occurring spontaneously or on exertion

Exclusion Criteria:

• Current smoker, or Ex-smoker with a >10 year pack history or having smoked within the past 6 months.

• Significant alternative diagnoses that may mimic or complicate asthma, in particular dysfunctional breathing, panic attacks, and overt psychosocial problems (if these are thought to be the major problem rather than in addition to severe asthma)

• Significant other primary pulmonary disorders in particular pulmonary embolism, pulmonary hypertension, interstitial lung disease and lung cancer

• Subjects with emphysema and bronchiectasis should only be excluded if this is thought to be the major pulmonary disorder rather than in addition to severe asthma

• Diagnosis or current investigation of occupational asthma

• Any subjects currently participating, or having participated within 3 months of the first dose in a study using a new molecular entity, or the first dose in any other study investigating drugs.

Related Conditions & MeSH terms

• Asthma

Locations

Country	Name	City	State
United Kingdom	Royal Brompton Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hydrogen Sulphide in Exhaled Breath	Level of hydrogen sulphide in exhaled breath measured as parts per billion	At baseline visit
Secondary	FEV1	Forced expiratory volume in one second as percent of predicted value (%)	At baseline visit
Secondary	FVC (Forced Vital Capacity)	Forced vital capacity as per cent of predicted	At 4 visits which occur during the study duration, up to 1 year
Secondary	Exhaled Nitric Oxide	Levels of nitric oxide in exhaled breath in parts per billion	At 4 visits which occur during the study duration, up to 1 year
Secondary	Blood Hydrogen Sulpide Level	Hydrogen Sulpide level measurements from blood	At 4 visits which occur during the study duration, up to 1 year