Role of Parasympathetic Activity in Mild to Severe Asthma With Fixed Airway Obstruction (PARASMA Study)

Not Applicable

Recruiting

• Conditions: Asthma; Airway Remodeling; Airway Obstruction; Parasympathetic Nervous System Diseases
• Interventions: Other: Placebo; Drug: Salbutamol plus Ipratropium Bromide; Drug: Salbutamol; Drug: Ipratropium Bromide

• Registration Number: NCT05550402
• Lead Sponsor: Hat Yai Medical Education Center

Brief Summary

In asthma, the significant role of pathogenesis is chronic airway inflammation, bronchial hyperresponsiveness, and variable airflow obstruction. Asthma with irreversible or fixed airflow obstruction (FAO) is a clinical phenotype resulting from chronic airway inflammation with having longer disease duration, suggesting that airway remodeling contributes to the decline in lung function seen in individuals with asthma. Although this condition frequently occurs in patients with severe asthma, there are pieces of evidence occurring in those with mild to moderate asthma. According to previous research, low lung function, FEV1 less than 60% predicted, is a robust independent predictor of subsequent asthma attacks and other asthma outcomes, including asthma control and SABA use. In a recent study, the patients with mild to moderate asthma who received mild to medium dosed inhaled corticosteroid plus long-acting beta-2 agonist with or without asthma control showed evidence of FAO with or without bronchodilator reversibility. Therefore parasympathetic activity may be affected by FAO in those patients. The autonomic nervous system plays an essential role in asthma, especially from the parasympathetic, promoting bronchoconstriction and regulating airway inflammation and remodeling. This study hypothesizes that a cholinergic mechanism may play a significant role in FAO across patients with mild, moderate, and severe asthma. This might increase the fundamental evidence leading to early-step treatment with anti-cholinergic medication in early asthma severity driven by FAO.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-19
• Study First Submitted QC: 2022-09-19
• Study First Posted: 2022-09-22
• Status Verified: 2024-02
• Study Start: 2024-02-17
• Last Update Submitted: 2024-02-17
• Last Update Posted: 2024-02-20
• Primary Completion: 2024-06-01
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Asthmatic patients classified by severity Mild (achieved control with using low-dose ICS or as-needed ICS-formoterol) or Moderate (achieved controlled with using low-dose ICS/LABA or Severe ((achieved controlled with using medium to high dose ICS/LABA)
• Post-bronchodilator (Salbutamol) FEV1/FVC ratio less than 0.75 or below the Lower Limit of Normal (LLN) and Post-bronchodilator (Salbutamol) FEV1 predicted < 80% with or without bronchodilator response
• History of smoking less than 10 pack-years or current smoking
• Patients who able to do spirometry without contraindication
• asthma control was defined by ACQ6 < 1.5

Exclusion Criteria

• Contraindication for spirometry
• Chest x-ray suggested any chronic lung diseased
• Contraindication for anticholinergic drug
• History of asthma exacerbation within 12 weeks before visit 1
• History of taking LAMA within 6 months before visit 1

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Visit 3, After predosed spirometry is done, the patients will be received 4 puffs of a placebo, and they will do spirometry at 30 minutes, 1 and 2 hours (Placebo arm).
Salbutamol plus ipratropium	Salbutamol plus Ipratropium Bromide	Visit 3, After predosed spirometry is done, the patients will be received 4 puffs of a placebo, and they will do spirometry at 30 minutes, 1 and 2 hours (Placebo arm). Then, the patients requested to be administered 4 puffs of ipratropium and 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours (Salbutamol plus ipratropium)
Salbutamol then ipratropium	Salbutamol	Visit 1, After predosed spirometry is done, the patients will be received 4 puffs of salbutamol. 30 minutes later, if they meet the criteria of fixed airway obstruction based on ATS criteria, then they will continue to undergo serial spirometry at 1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of ipratropium and do spirometry at 4.5 and 5 hours.
Salbutamol then ipratropium	Ipratropium Bromide	Visit 1, After predosed spirometry is done, the patients will be received 4 puffs of salbutamol. 30 minutes later, if they meet the criteria of fixed airway obstruction based on ATS criteria, then they will continue to undergo serial spirometry at 1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of ipratropium and do spirometry at 4.5 and 5 hours.
Ipratropium then salbutamol	Salbutamol	Visit 2, After predosed spirometry is done, the patients will be received 4 puffs of ipratropium they will continue to undergo serial spirometry at 30 minutes,1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours.
Ipratropium then salbutamol	Ipratropium Bromide	Visit 2, After predosed spirometry is done, the patients will be received 4 puffs of ipratropium they will continue to undergo serial spirometry at 30 minutes,1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours.

Primary Outcome Measures

Name	Time	Method
Average FEV1	6 hour	FEV1 determined from serial spirometry and calculated on the basis of area under the curve

Secondary Outcome Measures

Name	Time	Method
FEV1 at 6 h	6 hour	FEV1 at 6 hours post-dose
Maximum FEV1	6 hour	Maximum FEV1 over the 6-hour serial assessments

Trial Locations

Locations (1)

Hatyai Hospital; 🇹🇭 Hat Yai, Songkhla, Thailand