Post Deployment Related AsthmaPhase 2SEALSNCT05259904
Study to Improve Deployment Related Asthma by Using L-Citrulline Supplementation
A Phase 2 study testing L-citrulline in people with Post Deployment Related Asthma and Asthma, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Service men and women returning from deployment are significantly more likely to develop asthma and severe respiratory symptoms from airway obstruction. Why this happens is not well known, but exposure to diesel, burn pits, biomass smoke, and sandstorms are thought to play a role. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Post Deployment Related Asthma, Asthma
- What is being tested?
- L-citrulline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2023to Oct 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adequate completion of informed consent process with written documentation
- Male and female patients, 18 - 70 years old, inclusive
- Meets criteria for deployment related asthma or DRA (New onset of persistent respiratory symptoms of cough, dyspnea, wheezing and/or chest tightness during or after post-9/11/2001 military deployment to Southwest Asia, accompanied by a post-bronchodilator increase in FEV1 ≥ 12% and an increase in FEV1 ≥ 200 milliliters on pulmonary function testing and/or methacholine challenge showing airways hyperresponsiveness with a 20 percent drop in FEV1 (PC[-20] FEV1) ≤ 16 mg/mL. ) Historical results from previous studies or documented in clinical records within the last 24 months are acceptable alternatives
- Able to perform reproducible spirometry according to ATS criteria
- All racial/ethnic backgrounds may participate
- Smoking tobacco history ≤15 pack years and no smoking in the last 3 months
- Suboptimal asthma control at baseline (ACQ ≥ 0.5 or ACT<19)
Who cannot join
- Respiratory tract infection within the 4 weeks prior to Visit 0
- Pulmonary-related ER visit within the 4 weeks prior to Visit 0
- Oral or systemic corticosteroid burst (for any indication) within the 4 weeks prior to Visit 0. One-time doses, such as intra-articular injections into a shoulder or knee joint, require a 2-week washout prior to Visit 0
- Significant concomitant medical illness at the discretion of the PI, including (but not limited to) heart disease, cancer, uncontrolled diabetes, other chronic lung diseases
- Chronic renal failure (creatinine > 2.0) at Visit 0 (Associated with higher ADMA levels)
- Positive urine (or serum) pregnancy test at Visit 0 or at any time during the study
Show all 10Show fewer
- Intolerance or allergy to L-arginine or L-citrulline
- Concomitant use of PDE5 drugs or oral mononitrates
- Unable or unlikely to complete study assessments in the opinion of the Investigator
- Study intervention poses undue risk to patient in the opinion of the Investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
University of Colorado Asthma and Research Education Team contact
United States1 site, 1 recruiting
- Recruiting
National Jewish Health
Denver, Colorado, 80206
NJH SEALS Team, 303-398-1748, DeploymentLungRes@njhealth.org
Cecile Rose, MD, MPH
About this study
Official title: Study to Improve dEployment Related Asthma by Using L-citrulline Supplementation (SEALS)
Service men and women returning from deployment are significantly more likely to develop asthma and severe respiratory symptoms from airway obstruction. Why this happens is not well known, but exposure to diesel, burn pits, biomass smoke, and sandstorms are thought to play a role. Ultimately, patients with deployment related asthma develop a complex airway disease that does not respond well to standard asthma medications. Therefore, it is imperative that safe and affordable treatments that could improve quality of life and symptoms are studied.
It has been previously shown that adult patients with poorly controlled asthma have an abnormal regulation of an amino acid called L-arginine and airway nitric oxide (FeNO), a gaseous molecule normally produced in the airways of healthy people. In healthy people, nitric oxide is present in amounts that help keep the airways open. However, in some patients with asthma, nitric oxide and L-arginine are often low. The investigators' preliminary data in obese asthmatics show that L-citrulline, which is an amino acid that can be metabolized into L-arginine, improved lung function and asthma control, while increasing the levels of FeNO. This is potentially shifting the paradigm in how investigators think of asthma management, as rising FeNO is often thought of being a bad sign. Based on this, the study investigators hypothesize that an L-citrulline-based drug strategy will normalize nitric oxide metabolism, suppress oxidative inflammatory responses and improve airway function in obese patients with asthma. The study proposal presents a clinical trial approach to treat deployment related asthma patients using L-citrulline as an add-on therapy to improve asthma control. If this confirms the investigators' previous study results, the investigators will be in route for developing the only precision-based therapy available to treat this asthma phenotype. These study results will potentially show that L-citrulline is a safe, tolerable medication that can make a significant impact on the respiratory health of a large segment of our active and veteran population at a reasonable cost.
- Conditions
- Post Deployment Related Asthma, Asthma
- Being tested
- L-citrulline, Placebo
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDrug
7 weeks of treatment with 15 g/day of orally administered (powder form mixed with water) L-citrulline
PlaceboDrug
7 weeks of treatment with orally administered matching placebo (to 15 g/day of L-citrulline)
| Study group | Role | What they receive |
|---|---|---|
| L-citrulline | Experimental | L-citrulline with a dose of 15 g/day will be administered in powder form that is mixed with water and taken orally, continuously and daily for at least 7 weeks. Dispensed at Visits 0a/1. Washout period of 4 to 6 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. Receives: Drug: L-citrulline |
| Matching Placebo | Placebo comparator | Administered in powder form that is mixed with water and taken orally, continuously, and daily for at least 7 weeks. Dispensed at Visits 0a/. Washout period of 4 to 6 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Asthma Control Questionnaire
To determine L-citrulline efficacy, reduction in questionnaire scores determined
Measured: Through study completion, up to 22 weeks
Change in FeNO values
To determine L-citrulline efficacy, increase in FeNO values determined
Measured: Through study completion, up to 22 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study start8 Mar 2023
- Primary completionOct 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Deployment Related AsthmaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Jewish Health, United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Fernando Holguin, MD, MPH, Principal investigator, University of Colorado Denver- Anschutz Medical Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05259904
- Sponsor's protocol ID
- 21-2804
- Other IDs
- W81XWH2110677, 21-2804, E02466
- Acronym
- SEALS
- Status last verified
- Apr 2023
- First submitted
- 18 Feb 2022
- Last updated
- 6 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Improve dEployment Related Asthma by Using L-citrulline Supplementation (SEALS)
- ClinicalTrials.gov ID
- NCT05259904
- Acronym / sponsor ID
- SEALS / 21-2804
- Conditions
- Post Deployment Related Asthma, Asthma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Jewish Health, United States Department of Defense
- Study start
- 8 Mar 2023 (actual)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 2 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Service men and women returning from deployment are significantly more likely to develop asthma and severe respiratory symptoms from airway obstruction. Why this happens is not well known, but exposure to diesel, burn pits, biomass smoke, and sandstorms are thought to play a role. Ultimately, patients with deployment related asthma develop a complex airway disease that does not respond well to standard asthma medications. Therefore, it is imperative that safe and affordable treatments that could improve quality of life and symptoms are studied.
It has been previously shown that adult patients with poorly controlled asthma have an abnormal regulation of an amino acid called L-arginine and airway nitric oxide (FeNO), a gaseous molecule normally produced in the airways of healthy people. In healthy people, nitric oxide is present in amounts that help keep the airways open. However, in some patients with asthma, nitric oxide and L-arginine are often low. The investigators' preliminary data in obese asthmatics show that L-citrulline, which is an amino acid that can be metabolized into L-arginine, improved lung function and asthma control, while increasing the levels of FeNO. This is potentially shifting the paradigm in how investigators think of asthma management, as rising FeNO is often thought of being a bad sign. Based on this, the study investigators hypothesize that an L-citrulline-based drug strategy will normalize nitric oxide metabolism, suppress oxidative inflammatory responses and improve airway function in obese patients with asthma. The study proposal presents a clinical trial approach to treat deployment related asthma patients using L-citrulline as an add-on therapy to improve asthma control. If this confirms the investigators' previous study results, the investigators will be in route for developing the only precision-based therapy available to treat this asthma phenotype. These study results will potentially show that L-citrulline is a safe, tolerable medication that can make a significant impact on the respiratory health of a large segment of our active and veteran population at a reasonable cost.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-citrulline | Experimental | Drug: L-citrullineL-citrulline with a dose of 15 g/day will be administered in powder form that is mixed with water and taken orally, continuously and daily for at least 7 weeks. Dispensed at Visits 0a/1. Washout period of 4 to 6 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. |
| Matching Placebo | Placebo comparator | Drug: PlaceboAdministered in powder form that is mixed with water and taken orally, continuously, and daily for at least 7 weeks. Dispensed at Visits 0a/. Washout period of 4 to 6 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adequate completion of informed consent process with written documentation
- Male and female patients, 18 - 70 years old, inclusive
- Meets criteria for deployment related asthma or DRA (New onset of persistent respiratory symptoms of cough, dyspnea, wheezing and/or chest tightness during or after post-9/11/2001 military deployment to Southwest Asia, accompanied by a post-bronchodilator increase in FEV1 ≥ 12% and an increase in FEV1 ≥ 200 milliliters on pulmonary function testing and/or methacholine challenge showing airways hyperresponsiveness with a 20 percent drop in FEV1 (PC[-20] FEV1) ≤ 16 mg/mL. ) Historical results from previous studies or documented in clinical records within the last 24 months are acceptable alternatives
- Able to perform reproducible spirometry according to ATS criteria
- All racial/ethnic backgrounds may participate
Key exclusion criteria (10 listed)
- Respiratory tract infection within the 4 weeks prior to Visit 0
- Pulmonary-related ER visit within the 4 weeks prior to Visit 0
- Oral or systemic corticosteroid burst (for any indication) within the 4 weeks prior to Visit 0. One-time doses, such as intra-articular injections into a shoulder or knee joint, require a 2-week washout prior to Visit 0
- Significant concomitant medical illness at the discretion of the PI, including (but not limited to) heart disease, cancer, uncontrolled diabetes, other chronic lung diseases
- Chronic renal failure (creatinine > 2.0) at Visit 0 (Associated with higher ADMA levels)
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 |
|---|---|---|
| L-citrulline7 weeks of treatment with 15 g/day of orally administered (powder form mixed with water) L-citrulline | Drug | L-citrulline |
| Placebo7 weeks of treatment with orally administered matching placebo (to 15 g/day of L-citrulline) | Drug | Matching Placebo |
Primary outcome
Change in Asthma Control Questionnaire
Time frame: Through study completion, up to 22 weeks
To determine L-citrulline efficacy, reduction in questionnaire scores determined
Change in FeNO values
Time frame: Through study completion, up to 22 weeks
To determine L-citrulline efficacy, increase in FeNO values determined
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2023.
- Individual participant dataSharing planned: No
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.
University of Colorado Asthma and Research Education Team contact
Fernando Holguin, MD, MPH principal investigator
University of Colorado Denver- Anschutz Medical Campus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-citrulline in people with Post Deployment Related Asthma and Asthma, run by University of Colorado, Denver 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 7 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 6 Apr 2023. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact University of Colorado Asthma and Research Education Team (1-844-365-0852, asthmaresearh@ucdenver.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Asthma Control Questionnaire (time frame: Through study completion, up to 22 weeks). The study lists 2 primary outcomes in all. 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 6 Apr 2023.