Mild AsthmaGlutozNCT00287365
Genetic Susceptibility to Ozone in Mild Asthmatic Volunteers
A study testing ozone in people with Mild Asthma, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Recent reports have shown that people with asthma who have a particular gene, known as the GSTM1 null gene, are more susceptible to the effect of air pollutants. The purpose of this research study is to learn if volunteers who have asthma and have a GSTM1 null gene have increased response (change in lung function and… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Mild Asthma
- What is being tested?
- ozone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Nov 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- healthy volunteers with mild asthma
- Normal lung function,
- Oxygen saturation of > 94 %
- Normal blood pressure
Who cannot join
- A history of significant chronic illnesses
- Allergy to any medications which may be used or prescribed in the course of this study (albuterol, acetaminophen, aspirin or non-steroidal anti-inflammatory agents, corticosteroids, lactose, polyethylene glycol)
- Positive pregnancy test within 48 hours of the time of challenge
- Subjects currently taking medications which may impact the results of the ozone challenge, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) or suggest an ongoing illness (such as antibiotics).
- Mega doses of vitamins and supplements, homeopathic/naturopathic medicines
- Any acute, non-chronic, medical conditions occurring in the prior two weeks. Such illnesses must be totally resolved symptomatically for 2 weeks and documentation of normal lung function must be obtained.
Show all 18Show fewer
- Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with ozone inhalation challenge, will be a basis for exclusion.
- Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
- Use of systemic steroid therapy within the preceding 12 months.
- > 0.5 pack year history of tobacco use
- Use of inhaled steroids, cromolyn or leukotriene inhibitors initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy.
- Use of daily theophylline within the past month.
- Pregnancy or nursing a baby.
- Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- Exacerbation of asthma more than 2x/week which would be characteristic of a person with moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
- Dosing level of an inhaled steroid must be consistent with mild episodic asthma as outlined by the NHLBI NAEPP guidelines. Use of inhaled steroid at doses typically used for moderate or severe asthma will result in exclusion of that individual from the protocol.
- Students or staff members who work directly for the PI, Dr David Peden, are excluded from study participation
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Environmental Medicine, Asthma and Lung Biology
Chapel Hill, North Carolina, 27599
About this study
Official title: Glutathione S Transferase M1 (GSTM1) Genotype Associated Susceptibility to Airway Response to Ozone in Mild Asthmatic Volunteers.
Recent reports have shown that people with asthma who have a particular gene, known as the GSTM1 null gene, are more susceptible to the effect of air pollutants. The purpose of this research study is to learn if volunteers who have asthma and have a GSTM1 null gene have increased response (change in lung function and increase in lung cells collected from sputum) compared to volunteers with asthma who have the GSTM1 sufficient gene when challenged with 0.4 ppm ozone during intermittent exercise. The principal purpose of this study is to identify hyper-responsive, responsive and non-responsive groups of human subjects with mild asthma based on their airway neutrophilic response to ozone exposure, and to perform analyses on DNA from airway cells to explore possible differences in genetic profiles between the three groups. An additional pilot aim is to compare expression of a small number of specific genes of interest in a subset of ozone-responsive and ozone-non-responsive subjects with mild asthma.
Read the detailed description
Fifty volunteers with mild asthma will be recruited to undergo ozone challenge in the controlled exposure facility of the US EPA Human Studies Division (104 Mason Farm Road, Chapel Hill, NC) with 0.4ppm for 2 hours with moderate exercise alternating with rest. Endpoints will include genetic analysis for the GSTM1 genotype, sputum and spirometry changes pre and post exposure, and blood endpoints pre and post exposure.
TRAINING DAY: (at least 3 days prior to the ozone challenge) Eligible subjects will report to the research lab for a 3 hour training session.
- All female volunteers will undergo a urine pregnancy test.
- After informed consent is obtained, Measurement of orally exhaled nitric oxide will be obtained
- Subjects will perform spirometry.
- Subjects will exercise on a treadmill to determine the workload for the actual exposure.
- Finally the subject will undergo sputum induction following pretreatment with albuterol.
The sputum will be assessed for quality to determine continued eligibility. If a subject has provided an acceptable sputum sample within the prior 6 months this may be used as inclusion criteria rather than repeating the induction at this point. After subjects have demonstrated production of an adequate sputum sample, they will be scheduled for the ozone exposure visit.
24 HOURS PRIOR to the exposure day (Day 1): Subjects will be asked to refrain from smoking as well as drinking alcohol for 24 hours prior to Day 1 until after completion of Day 3.
- Subjects will have vital signs and oxygen saturation checked, including the symptom questionnaire.
- They will also undergo a physical examination of the ears, nose, throat and chest (lung sounds).
- Female volunteers will undergo urine pregnancy testing.
- Measurement of orally exhaled nitric oxide will be obtained.
- Spirometry testing will be performed.
- Subjects will have a sputum induction preceded by administration of 2 puffs of albuterol.
EXPOSURE DAY (at least 3 days after the training day):
- Subjects will be asked to arrive at the study site at approximately 8 AM and will undergo assessment of vital signs (temperature, pulse, respiratory rate, blood pressure), oxygen saturation, and symptom score assessment.
- A telemetry unit will be placed for cardiac monitoring during the exposure.
- Measurement of orally exhaled nitric oxide will be obtained prior to exposure and 4 hours after the end of the exposure
- Spirometry testing to rule out acute illness prior to the exposure.
- They will also undergo a physical examination of the ears, nose, throat and chest.
- Exposure sessions: The 0.4 ppm ozone exposure will be conducted in an ozone exposure chamber. Each subject will be exposed to 0.4 ppm ozone for 2 hours. During exposures, subjects will perform four 15 minute bouts of moderate exercise (minute ventilation or VE = 30 40 L/min) on a treadmill, each separated by 15 minutes of seated rest. Minute ventilation is measured for 2 to 3 minutes after about 4 minutes of exercise during the first exercise period, and again at about 12 minutes of exercise. It is then measured at about 12 minutes into each exercise period. Two subjects may be exposed simultaneously, in which case the exercise/rest periods will be alternated.
- Immediately post exposure and 4 hours after completion of exposure, subjects will have an assessment of vital signs, oxygen saturation, symptom score assessment and undergo spirometry evaluation.
- Venipuncture: 20 ml of blood will be collected for a CBC/ differential, assessment of blood monocyte phagocytic function and cell surface markers just prior to the exposure and 4 hours after the end of exposure. A portion of the sample will be used for genotyping.
- Induced sputum will be collected 6 hours after initiation of exposure after subjects have been premedicated with albuterol. The subjects will be observed at the study site until sputum induction is complete. Subjects will not be discharged home following the post-exposure sputum induction until FEV1 is within 90% of baseline values and vital signs are normal. Subjects not meeting safety criteria at the end of the exposure day will be admitted to the GCRC for overnight observation. 24 HOURS POST EXPOSURE (Day 3): The following morning, approximately 24 hours after exposure, the volunteer subject will be assessed directly at the study site. The subject will undergo spirometry, vital sign monitoring and symptom scoring.
STUDY DISCONTINUATION VISIT (5-10 days after exposure): The volunteer subject will again be assessed directly at the study site. The subject will undergo spirometry, vital sign monitoring and symptom scoring.
- Conditions
- Mild Asthma
- Being tested
- ozone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ozoneDrug
Also called O3
2 hour exposure to 0.4 ppm ozone
| Study group | Role | What they receive |
|---|---|---|
| 1-ozone | Experimental | Mildly asthmatic subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects Receives: Drug: ozone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post Ozone Change in Lung Function (FEV1) Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
Measured: 6 hours post exposure
Secondary outcomes (2)
Secondary Endpoints Include Post Ozone Airway PMN Influx Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
Measured: 6 hours post exposure
% Decrease in FVC in Asthmatics Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
Measured: 6 hours post exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2006 (estimated)
- Study startJan 2006
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mild AsthmaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Environmental Protection Agency (EPA)
- Responsible party
- Sponsor
- Investigators
- David B. Peden, MD, Principal investigator, University of NC Center for Environmental Medicine, Asthma and Lung Biology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00287365
- Sponsor's protocol ID
- GCRC-2371
- Other IDs
- NCCAM 1PO1AT002620
- Acronym
- Glutoz
- Status last verified
- Sep 2017
- First submitted
- 3 Feb 2006
- Last updated
- 13 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutathione S Transferase M1 (GSTM1) Genotype Associated Susceptibility to Airway Response to Ozone in Mild Asthmatic Volunteers.
- ClinicalTrials.gov ID
- NCT00287365
- Acronym / sponsor ID
- Glutoz / GCRC-2371
- Conditions
- Mild Asthma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Environmental Protection Agency (EPA)
- Study start
- Jan 2006
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 6 Feb 2006 (estimated)
- Results
- Posted 15 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent reports have shown that people with asthma who have a particular gene, known as the GSTM1 null gene, are more susceptible to the effect of air pollutants. The purpose of this research study is to learn if volunteers who have asthma and have a GSTM1 null gene have increased response (change in lung function and increase in lung cells collected from sputum) compared to volunteers with asthma who have the GSTM1 sufficient gene when challenged with 0.4 ppm ozone during intermittent exercise. The principal purpose of this study is to identify hyper-responsive, responsive and non-responsive groups of human subjects with mild asthma based on their airway neutrophilic response to ozone exposure, and to perform analyses on DNA from airway cells to explore possible differences in genetic profiles between the three groups. An additional pilot aim is to compare expression of a small number of specific genes of interest in a subset of ozone-responsive and ozone-non-responsive subjects with mild asthma.
Detailed description
Fifty volunteers with mild asthma will be recruited to undergo ozone challenge in the controlled exposure facility of the US EPA Human Studies Division (104 Mason Farm Road, Chapel Hill, NC) with 0.4ppm for 2 hours with moderate exercise alternating with rest. Endpoints will include genetic analysis for the GSTM1 genotype, sputum and spirometry changes pre and post exposure, and blood endpoints pre and post exposure.
TRAINING DAY: (at least 3 days prior to the ozone challenge) Eligible subjects will report to the research lab for a 3 hour training session.
- All female volunteers will undergo a urine pregnancy test.
- After informed consent is obtained, Measurement of orally exhaled nitric oxide will be obtained
- Subjects will perform spirometry.
- Subjects will exercise on a treadmill to determine the workload for the actual exposure.
- Finally the subject will undergo sputum induction following pretreatment with albuterol.
The sputum will be assessed for quality to determine continued eligibility. If a subject has provided an acceptable sputum sample within the prior 6 months this may be used as inclusion criteria rather than repeating the induction at this point. After subjects have demonstrated production of an adequate sputum sample, they will be scheduled for the ozone exposure visit.
24 HOURS PRIOR to the exposure day (Day 1): Subjects will be asked to refrain from smoking as well as drinking alcohol for 24 hours prior to Day 1 until after completion of Day 3.
- Subjects will have vital signs and oxygen saturation checked, including the symptom questionnaire.
- They will also undergo a physical examination of the ears, nose, throat and chest (lung sounds).
- Female volunteers will undergo urine pregnancy testing.
- Measurement of orally exhaled nitric oxide will be obtained.
- Spirometry testing will be performed.
- Subjects will have a sputum induction preceded by administration of 2 puffs of albuterol.
EXPOSURE DAY (at least 3 days after the training day):
- Subjects will be asked to arrive at the study site at approximately 8 AM and will undergo assessment of vital signs (temperature, pulse, respiratory rate, blood pressure), oxygen saturation, and symptom score assessment.
- A telemetry unit will be placed for cardiac monitoring during the exposure.
- Measurement of orally exhaled nitric oxide will be obtained prior to exposure and 4 hours after the end of the exposure
- Spirometry testing to rule out acute illness prior to the exposure.
- They will also undergo a physical examination of the ears, nose, throat and chest.
- Exposure sessions: The 0.4 ppm ozone exposure will be conducted in an ozone exposure chamber. Each subject will be exposed to 0.4 ppm ozone for 2 hours. During exposures, subjects will perform four 15 minute bouts of moderate exercise (minute ventilation or VE = 30 40 L/min) on a treadmill, each separated by 15 minutes of seated rest. Minute ventilation is measured for 2 to 3 minutes after about 4 minutes of exercise during the first exercise period, and again at about 12 minutes of exercise. It is then measured at about 12 minutes into each exercise period. Two subjects may be exposed simultaneously, in which case the exercise/rest periods will be alternated.
- Immediately post exposure and 4 hours after completion of exposure, subjects will have an assessment of vital signs, oxygen saturation, symptom score assessment and undergo spirometry evaluation.
- Venipuncture: 20 ml of blood will be collected for a CBC/ differential, assessment of blood monocyte phagocytic function and cell surface markers just prior to the exposure and 4 hours after the end of exposure. A portion of the sample will be used for genotyping.
- Induced sputum will be collected 6 hours after initiation of exposure after subjects have been premedicated with albuterol. The subjects will be observed at the study site until sputum induction is complete. Subjects will not be discharged home following the post-exposure sputum induction until FEV1 is within 90% of baseline values and vital signs are normal. Subjects not meeting safety criteria at the end of the exposure day will be admitted to the GCRC for overnight observation. 24 HOURS POST EXPOSURE (Day 3): The following morning, approximately 24 hours after exposure, the volunteer subject will be assessed directly at the study site. The subject will undergo spirometry, vital sign monitoring and symptom scoring.
STUDY DISCONTINUATION VISIT (5-10 days after exposure): The volunteer subject will again be assessed directly at the study site. The subject will undergo spirometry, vital sign monitoring and symptom scoring.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1-ozone | Experimental | Drug: ozoneMildly asthmatic subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- healthy volunteers with mild asthma
- Normal lung function,
- Oxygen saturation of > 94 %
- Normal blood pressure
Key exclusion criteria (18 listed)
- A history of significant chronic illnesses
- Allergy to any medications which may be used or prescribed in the course of this study (albuterol, acetaminophen, aspirin or non-steroidal anti-inflammatory agents, corticosteroids, lactose, polyethylene glycol)
- Positive pregnancy test within 48 hours of the time of challenge
- Subjects currently taking medications which may impact the results of the ozone challenge, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) or suggest an ongoing illness (such as antibiotics).
- Mega doses of vitamins and supplements, homeopathic/naturopathic medicines
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ozoneAlso: O32 hour exposure to 0.4 ppm ozone | Drug | 1-ozone |
Primary outcome
Post Ozone Change in Lung Function (FEV1) Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
Time frame: 6 hours post exposure
2 secondary outcomes
Secondary Endpoints Include Post Ozone Airway PMN Influx Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
Time frame: 6 hours post exposure
% Decrease in FVC in Asthmatics Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
Time frame: 6 hours post exposure
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UNC Center for Environmental Medicine, Asthma and Lung BiologyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David B. Peden, MD principal investigator
University of NC Center for Environmental Medicine, Asthma and Lung Biology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ozone in people with Mild Asthma, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post Ozone Change in Lung Function (FEV1) Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects (time frame: 6 hours post exposure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2017.