Study to Improve Deployment Related Asthma by Using L-Citrulline Supplementation (SEALS)
Primary Purpose
Post Deployment Related Asthma, Asthma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
L-citrulline
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Post Deployment Related Asthma
Eligibility Criteria
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
Sites / Locations
- National Jewish HealthRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
L-citrulline
Matching Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Change in Asthma Control Questionnaire
To determine L-citrulline efficacy, reduction in questionnaire scores determined
Change in FeNO values
To determine L-citrulline efficacy, increase in FeNO values determined
Secondary Outcome Measures
Full Information
NCT ID
NCT05259904
First Posted
February 18, 2022
Last Updated
April 4, 2023
Sponsor
University of Colorado, Denver
Collaborators
National Jewish Health, United States Department of Defense
1. Study Identification
Unique Protocol Identification Number
NCT05259904
Brief Title
Study to Improve Deployment Related Asthma by Using L-Citrulline Supplementation
Acronym
SEALS
Official Title
Study to Improve dEployment Related Asthma by Using L-citrulline Supplementation (SEALS)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 8, 2023 (Actual)
Primary Completion Date
October 2028 (Anticipated)
Study Completion Date
October 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Jewish Health, United States Department of Defense
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Deployment Related Asthma, Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
75 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
L-citrulline
Arm Type
Experimental
Arm Description
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.
Arm Title
Matching Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
L-citrulline
Intervention Description
7 weeks of treatment with 15 g/day of orally administered (powder form mixed with water) L-citrulline
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
7 weeks of treatment with orally administered matching placebo (to 15 g/day of L-citrulline)
Primary Outcome Measure Information:
Title
Change in Asthma Control Questionnaire
Description
To determine L-citrulline efficacy, reduction in questionnaire scores determined
Time Frame
Through study completion, up to 22 weeks
Title
Change in FeNO values
Description
To determine L-citrulline efficacy, increase in FeNO values determined
Time Frame
Through study completion, up to 22 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
University of Colorado Asthma and Research Education Team
Phone
1-844-365-0852
Email
asthmaresearh@ucdenver.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando Holguin, MD, MPH
Organizational Affiliation
University of Colorado Denver- Anschutz Medical Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
NJH SEALS Team
Phone
303-398-1748
Email
DeploymentLungRes@njhealth.org
First Name & Middle Initial & Last Name & Degree
Cecile Rose, MD, MPH
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Improve Deployment Related Asthma by Using L-Citrulline Supplementation
We'll reach out to this number within 24 hrs