Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

GSNOR Phenotyping/GSNO Challenge

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03926741
Recruitment Status : Recruiting
First Posted : April 24, 2019
Last Update Posted : May 16, 2019
Sponsor:
Collaborators:
University Hospitals Cleveland Medical Center
Case Western Reserve University
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
James Reynolds, University Hospitals Cleveland Medical Center

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.


Condition or disease Intervention/treatment Phase
Asthma Healthy Volunteers Drug: GSNO Early Phase 1

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Methods to Identify and Treat Severe Asthma Patients Project 1: GSNOR Phenotyping and GSNO Challenge
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : March 2, 2021
Estimated Study Completion Date : March 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: GSNOR Challenge testing
patient will use a nebulizer to inhale (breathe in) a solution of GSNO followed by repeated measurements of airway function (breathing tests)
Drug: GSNO
patient will use a nebulizer to inhale (breathe in) a solution of GSNO followed by repeated measurements of airway function (breathing tests)




Primary Outcome Measures :
  1. Airway GSNOR comparison [ Time Frame: Baseline ]
    Airway GSNOR will be compared among the two different groups (Asthma and Healthy Volunteers).

  2. Airway GSNOR comparison [ Time Frame: 3 months ]
    Airway GSNOR will be compared among the two different groups (Asthma and Healthy Volunteers).


Secondary Outcome Measures :
  1. Fractional Exhaled Nitric Oxide (FeNO) levels changes [ Time Frame: Baseline ]
    FeNO measurements will be compared among the two different groups (Asthma and Healthy Volunteers).

  2. Fractional Exhaled Nitric Oxide (FeNO) levels changes [ Time Frame: 3 months ]
    FeNO measurements will be compared among the two different groups (Asthma and Healthy Volunteers).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For subjects with Asthma

  • Adult males or females age ≥ 18 and ≤ 50 years at the time of enrollment
  • Physician diagnosis of asthma for at least one year
  • FEV1 bronchodilator reversibility > 12% or methacholine PC20 )provocative concentration causing a 20% fall) < 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-smokers
  • 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

Exclusion Criteria: General (applying to all participants)

  • > 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 subject unsuitable for study participation
  • History of premature birth before 35 weeks gestation
  • Planning to relocate away from the clinical center (Cleveland, Ohio) 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)
  • More than 3 exacerbations within the past 6 months
  • Intubated for asthma within the past 12 months
  • Respiratory or other infection requiring systemic antibiotics within the previous 14 days (can be rescreened)
  • Current use of a vitamin K antagonist (warfarin) or other anticoagulant (e.g., heparin, clopidogrel, enoxaparin or dalteparin)
  • Current use of beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates
  • Inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g., sickle cell)
  • Any illness, condition or recent surgeries that may increase the risks associated with the study
  • Participation in any investigational drug study other than the Airway pH ( potential hydrogen) Study within the 4 week period prior to screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03926741


Contacts
Layout table for location contacts
Contact: Marie Abdul-Karim 216-368-8647 mla17@case.edu
Contact: Laurie Logan 216-844-7927 Laurie.Logan@UHhospitals.org

Locations
Layout table for location information
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Marie Abdul-Karim    216-368-8647    mla@case.edu   
Principal Investigator: Kristie Ross, MD         
Sub-Investigator: James Reynolds, PhD         
Sponsors and Collaborators
James Reynolds
University Hospitals Cleveland Medical Center
Case Western Reserve University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Kristie Ross University Hospitals Cleveland Medical Center
Principal Investigator: James Reynolds Case Western Reserve University

Publications:
Jenkins KT. Nitrogen compounds. Hamilton & hardy's industrial toxicology. John Wiley & Sons, Inc.; 2015:363-370.

Layout table for additonal information
Responsible Party: James Reynolds, Professor of Anesthesiology & Perioperative Medicine, University Hospitals Cleveland Medical Center
ClinicalTrials.gov Identifier: NCT03926741     History of Changes
Other Study ID Numbers: 12-17-11
5P01HL128192 ( U.S. NIH Grant/Contract )
First Posted: April 24, 2019    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial, after deidentification and analysis will be shared.
Supporting Materials: Statistical Analysis Plan (SAP)
Clinical Study Report (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.

Layout table for additional information
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

Additional relevant MeSH terms:
Layout table for MeSH terms
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases