Inpatient Clinical Trial of NAC (ICON)

The purpose of this study is to determine the beneficial effect of n-acetylcysteine (NAC), an inhaled medication that breaks down mucus, on lung function. NAC is a medication approved by the US Food and Drug Administration (FDA) for the treatment of chronic diseases of the respiratory system, including asthma. With CT lung imaging, the investigators seek to identify a subgroup of patients with asthma with a 'mucus' profile. This is a single-arm study which means all participants will receive the same treatment.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: N-acetylcysteine

Detailed Description

N-acetylcystine (NAC) is a mucolytic medication, meaning that it breaks apart mucus. Investigators know that mucus is a factor in severe asthma attacks. However, mucus may be a factor in chronic severe asthma as well. This role has been hard to prove because of difficulty in showing that mucus occludes the lumen in chronic severe disease. Using a novel approach of scoring mucus occlusion, investigators have used CT imaging to uncover that a majority of people with severe asthma have at least one lung segment with a mucus plug and 27% have more than four lung segments with mucus plugs.

Historically, studies of mucolytics, like NAC, have not shown benefit in other obstructive lung diseases, like COPD. However, utilizing CT mucus scores as a biomarker, investigators believe that mucolytic treatment may prove useful for those with significant mucus impaction.

This is a single-arm study of participants with asthma who also have evidence of mucus in their lungs as determined by CT imaging. Investigators hypothesize that by treating asthmatics, chosen based on the presence of mucus in the airways, with a mucolytic like NAC, will result in an improvement of lung function.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female between the ages of 18 and 80 years of age at Visit 1
2. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
3. Able to perform reproducible spirometry according to ATS criteria
4. Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥ 12% or hyperreactivity to methacholine reflected by a methacholine PC20 ≤ 16 mg/mL)
5. Clinical history of asthma per patient report or medical record
6. Pre-bronchodilator FEV1 > 35% predicted
7. Post-bronchodilator FEV1 > 40% but < 90% predicted
8. Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater
9. CT mucus score > 3

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
2. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
3. Smoking of tobacco or other recreational inhalants in last year and/or >10 pack-year smoking history
4. Current participation in an investigational drug trial
5. Other chronic pulmonary disorders, including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction (that is the sole cause of respiratory symptoms and at the PI's discretion), severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways
6. Unwillingness to follow study procedures
7. History of allergy or intolerance to study drug
8. Any other criteria that places the subject at unnecessary risk according to the judgment of the Principal Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: N-acetylcysteine; This study will look at the effects of a medication, called n-acetylcysteine or NAC, on lung function. NAC is already approved for use in people with chronic airway conditions, including asthma. However, it is not known who this medication works best in. We believe this medication will likely have the most benefit in people with asthma that have mucus in their airways or "mucus plugging." Initial study procedures will include lung function measurements, a low dose CT scan, a blood draw, and a sputum induction. The CT lung imaging will identify asthmatics with mucus plugs.

Drug: N-acetylcysteine; Research participants that meet the study inclusion criteria will be admitted to a medical-surgical ward in Moffitt-Long Hospital (UCSF Medical Center) for 6 days and 5 nights and treated with an inhaled mixture of NAC and albuterol four times per day spaced at 4 to 6 hours apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) Measurement	Post-treatment FEV1 is reported. FEV1 is measured via spirometry.	end of the one week treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Computed Tomography (CT) Scan Mucus Score	Post-treatment CT mucus scores will be compared to pre-treatment CT mucus score	From the start of the one week treatment period to the three month follow-up

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Hays SR, Fahy JV. The role of mucus in fatal asthma. Am J Med. 2003 Jul;115(1):68-9. doi: 10.1016/s0002-9343(03)00260-2. No abstract available.
• DUNNILL MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13(1):27-33. doi: 10.1136/jcp.13.1.27.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2018
• Primary Completion (Actual): July 13, 2018
• Study Completion (Actual): October 6, 2018

Study Registration Dates

• First Submitted: April 12, 2018
• First Submitted That Met QC Criteria: July 6, 2018
• First Posted (Actual): July 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 17-24231; P01HL128191 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No