Trial Outcomes & Findings for GSNOR Phenotyping/GSNO Challenge in Severe Asthma (NCT NCT03926741)

Last Updated: 2026-05-20

Results Overview

The Fractional expired Nitric Oxide, FeNO, is measured by exhaling into a tube connected to the monitoring device. Nitric oxide is one of the breakdown products of GSNO so measuring it in the breath indicates how fast GSNO is metabolized by the lung

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

48 participants

Primary outcome timeframe

Approximately 70-80 minutes with measurements taken before and at 10 min intervals up to 1 h after GSNO inhalation

Results posted on

2026-05-20

Participant Flow

Recruitment involved screening hospital clinic lists, partnering with Clinical Research Centers, advertising in social media, and study personnel participating in community health events.

The study had 3 visits: Visit 1 Health Screen. Consented subjects were removed (withdrawn/not completed) from study based on inability to perform lung function testing, loss of asthma symptoms, or safety concerns. Visit 2 Bronchoscopy. Visit 3 GSNO administration and respiratory testing. Note: 3 individuals with asthma were exempted from Visit 2 as a result of pandemic-era restrictions on conducting Research Bronchoscopies.

Participant milestones

Participant milestones
Measure	GSNO Challenge - Healthy Subjects determined to have normal lung function and no chronic disease condition. Each individual, used a nebulizer to inhale a GSNO solution. Drug exposure was followed by repeated measurements of airway function.	GSNO Challenge - Asthma Subjects determined to have Stable Asthma defined by GINA criteria. Each individual, used a nebulizer to inhale a GSNO solution. Drug exposure was followed by repeated measurements of airway function.
Overall Study STARTED	10	38
Overall Study COMPLETED	10	19
Overall Study NOT COMPLETED	0	19

Reasons for withdrawal

Reasons for withdrawal
Measure	GSNO Challenge - Healthy Subjects determined to have normal lung function and no chronic disease condition. Each individual, used a nebulizer to inhale a GSNO solution. Drug exposure was followed by repeated measurements of airway function.	GSNO Challenge - Asthma Subjects determined to have Stable Asthma defined by GINA criteria. Each individual, used a nebulizer to inhale a GSNO solution. Drug exposure was followed by repeated measurements of airway function.
Overall Study Failed screening visit	0	10
Overall Study Change in health status	0	6
Overall Study Withdrawal by Subject	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	0	1

Baseline Characteristics

GSNOR Phenotyping/GSNO Challenge in Severe Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSNO Challenge - Healthy n=10 Participants Subjects determined to have normal lung function and no chronic disease condition	GSNO Challenge - Asthma n=19 Participants Subjects determined to have Stable Asthma defined by GINA criteria	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=30 Participants	0 Participants n=30 Participants	0 Participants n=60 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=30 Participants	19 Participants n=30 Participants	29 Participants n=60 Participants
Age, Categorical >=65 years	0 Participants n=30 Participants	0 Participants n=30 Participants	0 Participants n=60 Participants
Sex: Female, Male Female	7 Participants n=30 Participants	12 Participants n=30 Participants	19 Participants n=60 Participants
Sex: Female, Male Male	3 Participants n=30 Participants	7 Participants n=30 Participants	10 Participants n=60 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=30 Participants	1 Participants n=30 Participants	1 Participants n=60 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=30 Participants	18 Participants n=30 Participants	28 Participants n=60 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=30 Participants	0 Participants n=30 Participants	0 Participants n=60 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=30 Participants	0 Participants n=30 Participants	0 Participants n=60 Participants
Race (NIH/OMB) Asian	1 Participants n=30 Participants	1 Participants n=30 Participants	2 Participants n=60 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=30 Participants	0 Participants n=30 Participants	0 Participants n=60 Participants
Race (NIH/OMB) Black or African American	0 Participants n=30 Participants	3 Participants n=30 Participants	3 Participants n=60 Participants
Race (NIH/OMB) White	9 Participants n=30 Participants	14 Participants n=30 Participants	23 Participants n=60 Participants
Race (NIH/OMB) More than one race	0 Participants n=30 Participants	1 Participants n=30 Participants	1 Participants n=60 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=30 Participants	0 Participants n=30 Participants	0 Participants n=60 Participants
Region of Enrollment United States · Subjects completed enrollment at Ohio Site	10 Participants n=30 Participants	1 Participants n=30 Participants	11 Participants n=60 Participants
Region of Enrollment United States · Subjects completed enrollment at Indiana Site	0 Participants n=30 Participants	18 Participants n=30 Participants	18 Participants n=60 Participants
Disease status: Healthy/Disease Healthy	10 Participants n=30 Participants	0 Participants n=30 Participants	10 Participants n=60 Participants
Disease status: Healthy/Disease Asthma	0 Participants n=30 Participants	19 Participants n=30 Participants	19 Participants n=60 Participants

PRIMARY outcome

Timeframe: Approximately 70-80 minutes with measurements taken before and at 10 min intervals up to 1 h after GSNO inhalation

Outcome measures

Outcome measures
Measure	GSNO Challenge - Healthy n=10 Participants Subjects determined to have normal lung function and no chronic disease condition	GSNO Challenge - Asthma n=19 Participants Subjects determined to have Stable Asthma defined by GINA criteria
FeNO Baseline FeNO	14.3 parts per billion Standard Deviation 9.1	34.3 parts per billion Standard Deviation 37.6
FeNO 30 min post GSNO	36.0 parts per billion Standard Deviation 21.4	49 parts per billion Standard Deviation 34.7
FeNO 60 min post GSNO	25 parts per billion Standard Deviation 18.3	42 parts per billion Standard Deviation 34.8

PRIMARY outcome

Timeframe: Approximately 1-2 minutes for each test with testing conducted before and after GSNO administration

The Forced expiratory Volume 1, is the volume of air expired (exhaled) in one second. It is recorded before and after GSNO administration. Subjects breathe through a tube to inhale and then blast exhale. The FeV1 is a standard measure of lung function.

Outcome measures

Outcome measures
Measure	GSNO Challenge - Healthy n=10 Participants Subjects determined to have normal lung function and no chronic disease condition	GSNO Challenge - Asthma n=19 Participants Subjects determined to have Stable Asthma defined by GINA criteria
Change in FeV1 Baseline	3.55 liters Standard Deviation 1.20	3.21 liters Standard Deviation 1.01
Change in FeV1 post GSNO	3.57 liters Standard Deviation 1.19	3.27 liters Standard Deviation 0.99

SECONDARY outcome

Timeframe: Lung biopsies were obtained during bronchoscopy

Population: Analyzable tissue not available from all subjects

Endobronchial biopsies from subjects who received GSNO were analyzed by Visium HD spatial transcriptomics. Batch analyses were conducted at the the end of the study. The measuments focused on 3 specific enzymes, AKR1A1, ADH5 and CBR1, involved in the breakdown of GSNO. This assessment was hampered by a low number of usable specimens.

Outcome measures

Outcome measures
Measure	GSNO Challenge - Healthy n=3 Participants Subjects determined to have normal lung function and no chronic disease condition	GSNO Challenge - Asthma n=6 Participants Subjects determined to have Stable Asthma defined by GINA criteria
Expression of GSNO Metabolic Enzymes in Human Airways AKR1A1 expression	938 relative flouresence units (RFU) Standard Deviation 568	1062 relative flouresence units (RFU) Standard Deviation 1429
Expression of GSNO Metabolic Enzymes in Human Airways ADH5 expression	96 relative flouresence units (RFU) Standard Deviation 84	115 relative flouresence units (RFU) Standard Deviation 119
Expression of GSNO Metabolic Enzymes in Human Airways CBR1	376 relative flouresence units (RFU) Standard Deviation 263	308 relative flouresence units (RFU) Standard Deviation 279

Adverse Events

GSNO Challenge - Healthy

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

GSNO Challenge - Asthma

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	GSNO Challenge - Healthy n=10 participants at risk Subjects determined to have normal lung function and no chronic disease condition. Adverse events were recorded during/after Visits 2 and 3 10 subjects completed Visit 2 and Visit 3 Therefore, Total at Risk subjects in this arm = 10	GSNO Challenge - Asthma n=21 participants at risk Subjects determined to have Stable Asthma defined by GINA criteria. Adverse events were recorded during/after Visits 2 and 3. The number of subjects at risk varies between Visit 2 and 3 because: 1. there were 2 subjects that completed Visit 2 but did not complete Visit 3 2. there were 16 subjects that completed Visit 2 and Visit 3 3. there were 3 subjects that completed Visit 3 Therefore, the Total at Risk subjects in this arm = 21 with 18 At Risk during Visit 2 and 19 At Risk during Visit 3.
Respiratory, thoracic and mediastinal disorders Visit 2 Airway/Chest	10.0% 1/10 • Number of events 2 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.	77.8% 14/18 • Number of events 42 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.
Nervous system disorders Visit 2 CNS	10.0% 1/10 • Number of events 1 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.	22.2% 4/18 • Number of events 4 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.
General disorders Visit 2 Systemic/Non-Specific	10.0% 1/10 • Number of events 1 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.	38.9% 7/18 • Number of events 8 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.
Respiratory, thoracic and mediastinal disorders Visit 3 Airway/Chest	10.0% 1/10 • Number of events 1 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.	47.4% 9/19 • Number of events 15 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.
Nervous system disorders Visit 3 CNS	10.0% 1/10 • Number of events 1 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.	0.00% 0/19 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.
General disorders Visit 3 Systemic/Non-Specific	0.00% 0/10 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.	47.4% 9/19 • Number of events 13 • The data collection period was 2 months. Adverse event data were collected up to 7 days after Visit 2 (bronchoscopy) and 24 h after Visit 3 (GSNO administration). There was a maximum interval of 56 days between Visit 2 and Visit 3.

Additional Information

Dr. James D. Reynolds

Case Western Reserve University

Phone: 216-368-5727

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place