GSNOR Phenotyping/GSNO Challenge in Severe Asthma

NCT03926741 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 12-17-115P01HL158507
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

Brief Summary

Asthma is caused by or worsened by different things in different people. It is because of these differences that not all people with asthma respond the same to all treatments and medicines. If the investigators can better identify the changes in the airways or breathing pipes in patients with asthma, the investigators may be able to help patients make better choices about the medicines or treatments that are most likely to work best for each patient. This research study is about one specific factor that is known to affect asthma in some patients. It involves an increase in the activity of an enzyme that is in people's airways. An enzyme is something that helps a chemical reaction to occur. The enzyme the investigators are studying in this research study is called GSNOR (S-nitrosoglutathione reductase) , and when the activity of this enzyme is increased, the result is that there is less GSNO (S-nitrosoglutathione) . GSNO is a chemical that protects people's airways. The initials stand for S-nitrosoglutathione, (pronounced s-nahy-troh-soh-gloo-tuh-thahy-ohn), and it is naturally produced by the body. It has an important role in regulating respiratory function (breathing) and preventing inflammation (swelling) in the respiratory tract (throat, airways, and lungs). The amount of GSNO found in the body is controlled by the enzyme GSNOR (S-nitrosoglutathione reductase). GSNOR breaks down GSNO. Too much GSNOR leads to low levels of GSNO, and that can cause inflammation (swelling) and loss of airway function in some asthma patients. The only way to measure GSNOR levels currently is with a bronchoscopy procedure where a scope is inserted into the patient's airways, often under sedation. This research study is being done to test the accuracy of another type of test that can be done in the doctor's office, rather than in a procedure area. This non-invasive diagnostic test, called a GSNO Challenge test, may be able to identify which asthma patients have increased activity of the airway enzyme GSNOR. The investigators are also studying the phenotypes (observable traits) in asthma patients with increased levels of GSNOR. If this research study is successful, in the future (after this research study is done). The investigators may be able to offer a cost-effective and non-invasive way to identify patients who have higher GSNOR activity levels and offer personalized treatments. The GSNO Challenge test includes giving an investigational drug to breathe in (inhale). The investigational drug is GSNO. "Investigational" means the drug is not approved by any regulatory agencies including the Food and Drug Administration (FDA), and is still being tested for safety and effectiveness. The research is registered with the FDA, but again the GSNO treatment in this study (administered during the GSNO challenge testing) is not an approved treatment or diagnostic test for asthma.

Conditions

Asthma; Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• Airway GSNOR comparison

  Airway GSNOR will be compared among the two different groups (Asthma and Healthy Volunteers).

  Baseline

• Airway GSNOR comparison

  Airway GSNOR will be compared among the two different groups (Asthma and Healthy Volunteers).

  3 months

Secondary Outcomes (2)

• Fractional Exhaled Nitric Oxide (FeNO) levels changes

  Baseline

• Fractional Exhaled Nitric Oxide (FeNO) levels changes

  3 months

Study Arms (1)

GSNOR Challenge testing

EXPERIMENTAL

patient will use a nebulizer to inhale (breathe in) a solution of GSNO followed by repeated measurements of airway function (breathing tests)

Drug: GSNO

Interventions

GSNO DRUG

patient will use a nebulizer to inhale (breathe in) a solution of GSNO followed by repeated measurements of airway function (breathing tests)

GSNOR Challenge testing

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For subjects with Asthma
• Adult males or females age ≥ 18 and ≤ 50 years at the time of enrollment
• Non-smoker
• Physician diagnosis of asthma for at least one year
• FEV1 bronchodilator reversibility \> 12% or methacholine PC20 \< 16 mg/ml (historical methacholine data from previous NIH trials including SARP and AsthmaNet will be allowed)
• Baseline post maximal bronchodilator FEV1 \>55% predicted
• Healthy Volunteers
• Adult males or females age ≥ 18 and ≤ 50 years at time of enrollment
• Non-smoker
• No history of asthma, chronic obstructive pulmonary disease (COPD), or other chronic lung disease
• No history of severe allergic/atopic disease requiring immunotherapy or immunomodulators

You may not qualify if:

• \> 5 pack year smoking history
• Body mass index (BMI) \> 45
• Unable to perform repeatable consistent efforts in pulmonary function testing
• Individuals with prior diagnosis of vocal cord dysfunction or an anatomic anomaly that would increase the risks associated with the bronchoscopy procedure
• Prior diagnosis of cystic fibrosis, COPD, or other additional lung disease that in the investigator's opinion would make participant unsuitable for study participation
• History of premature birth before 35 weeks gestation
• Planning to relocate away from the clinical center (Cleveland, Ohio or central Indiana) area before study completion
• Lack of reliable communications channel (hard-wire phone, cell phone, email for follow-up contacts after bronchoscopy)
• Allergic to anesthetic medication(s) that would prevent participation in the study's bronchoscopy
• Blood pressure parameters outside the normal range of 90-180 mm Hg systolic and 50-100 mm Hg diastolic at time of screening
• Individuals with diabetes mellitus (type 1 or type 2)
• Individuals with renal failure or creatinine \> 1.8 mg/dl at time of screening
• Individuals who are pregnant, breastfeeding, or are unwilling to use a medically acceptable method of birth control (as indicated on the Birth Control Methods Reference Card) from the time of consent until the end of the study to avoid pregnancy
• Individuals who report additional chronic diseases requiring medication of the heart, lungs, kidney, liver, brain, etc., or afflicted with any acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study such as coronary artery disease
• Asthma exacerbation requiring oral corticosteroids within the previous 30 days (can be rescreened)

Sponsors & Collaborators

• James Reynolds: lead
• University Hospitals Cleveland Medical Center: collaborator
• Case Western Reserve University: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

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MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Kristie Ross, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Anesthesiology & Perioperative Medicine

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: April 24, 2019
• Study Start: April 30, 2019
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR
• Time Frame: Available Immediately following publication. No end date
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

US (2)