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

NCT05550402 | Recruiting

• 1 other identifier: 454554
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Airway Obstruction; Airway Remodeling; Parasympathetic Nervous System Diseases

Keywords

asthma; fixed airway obstruction; spirometry; parasympathetic activity; well controlled

Outcome Measures

Primary Outcomes (1)

• Average FEV1

  FEV1 determined from serial spirometry and calculated on the basis of area under the curve

  6 hour

Secondary Outcomes (2)

• FEV1 at 6 h

  6 hour

• Maximum FEV1

  6 hour

Study Arms (4)

Salbutamol then ipratropium

ACTIVE COMPARATOR

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.

Drug: Salbutamol; Drug: Ipratropium Bromide

Ipratropium then salbutamol

ACTIVE COMPARATOR

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.

Drug: Salbutamol; Drug: Ipratropium Bromide

Salbutamol plus ipratropium

ACTIVE COMPARATOR

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)

Drug: Salbutamol plus Ipratropium Bromide

Placebo

PLACEBO COMPARATOR

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).

Other: Placebo

Interventions

Salbutamol DRUG

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.

Also known as: ventolin

Ipratropium then salbutamol; Salbutamol then ipratropium

Ipratropium Bromide DRUG

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.

Also known as: Atrovent

Ipratropium then salbutamol; Salbutamol then ipratropium

Salbutamol plus Ipratropium Bromide DRUG

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 arm)

Salbutamol plus ipratropium

Placebo OTHER

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).

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hat Yai Medical Education Center: lead

Study Sites (1)

Hatyai Hospital

Hat Yai, Changwat Songkhla, 90110, Thailand

RECRUITING

MeSH Terms

Conditions

Asthma; Airway Obstruction; Airway Remodeling; Autonomic Nervous System Diseases

Interventions

Albuterol; Ipratropium

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiratory Insufficiency; Respiration Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Narongwit Nakwan, M.D.

  Hatyai medical Education Center, Hatyai Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Narongwit Nakwan, M.D.

CONTACT

0818984566; naronak@hotmail.com

Pattarawadee Taptawee, R.N.

CONTACT

taptawee@hotmail.co.th

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asst. Prof.

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 22, 2022
• Study Start: February 17, 2024
• Primary Completion: June 1, 2024
• Study Completion: June 30, 2024
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

TH (1)