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Study to Improve Deployment Related Asthma by Using L-Citrulline Supplementation (SEALS)

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: NCT05259904
Recruitment Status : Recruiting
First Posted : March 2, 2022
Last Update Posted : April 6, 2023
National Jewish Health
United States Department of Defense
Information provided by (Responsible Party):
University of Colorado, Denver

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Post Deployment Related Asthma Asthma Drug: L-citrulline Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study to Improve dEployment Related Asthma by Using L-citrulline Supplementation (SEALS)
Actual Study Start Date : March 8, 2023
Estimated Primary Completion Date : October 2028
Estimated Study Completion Date : October 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: L-citrulline
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.
Drug: L-citrulline
7 weeks of treatment with 15 g/day of orally administered (powder form mixed with water) L-citrulline

Placebo Comparator: Matching Placebo
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.
Drug: Placebo
7 weeks of treatment with orally administered matching placebo (to 15 g/day of L-citrulline)

Primary Outcome Measures :
  1. Change in Asthma Control Questionnaire [ Time Frame: Through study completion, up to 22 weeks ]
    To determine L-citrulline efficacy, reduction in questionnaire scores determined

  2. Change in FeNO values [ Time Frame: Through study completion, up to 22 weeks ]
    To determine L-citrulline efficacy, increase in FeNO values determined

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • 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

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): NCT05259904

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Contact: University of Colorado Asthma and Research Education Team 1-844-365-0852 asthmaresearh@ucdenver.edu

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United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: NJH SEALS Team    303-398-1748    DeploymentLungRes@njhealth.org   
Principal Investigator: Cecile Rose, MD, MPH         
Sponsors and Collaborators
University of Colorado, Denver
National Jewish Health
United States Department of Defense
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Principal Investigator: Fernando Holguin, MD, MPH University of Colorado Denver- Anschutz Medical Campus
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT05259904    
Other Study ID Numbers: 21-2804
W81XWH2110677 ( Other Grant/Funding Number: Department of Defense/USAMRAA )
21-2804 ( Other Identifier: COMIRB )
E02466 ( Other Identifier: USAMRDC ORP HRPO )
First Posted: March 2, 2022    Key Record Dates
Last Update Posted: April 6, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases