AsthmaPhase 2SANDIANCT03885245
Supplementing L-citrulline to Overweight Late Asthma oNset Phenotypes
A Phase 2 study testing L-ctirulline in people with Asthma and Obesity, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Patients with obese late onset (after childhood) asthma can have lower FeNO levels, yet be highly symptomatic and poorly responsive to inhaled steroids. This is a common asthma phenotype, particularly among females. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- What is being tested?
- L-ctirulline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2021to 30 Jun 2026
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adequate completion of informed consent process
- Male and female patients
- Physician diagnosis of asthma
- Able to perform reproducible spirometry according to ATS criteria
- Pre-bronchodilator FEV1 >/= 50% of predicted at Visit 0
- Confirmation of asthma
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- All racial/ethnic backgrounds may participate.
- BMI >/= 30
- Regular treatment with ICS or ICS/LABA or LAMA combination medication for at least 1 month; participants can be on biologics.
- Smoking history </= 10 pack years and no smoking in the last 3 months
- Age of asthma onset (diagnosis) >/= 12 years
- FeNO </= 30 ppb
- ACQ >/= 0.50 or ACT </=19
Who cannot join
- Respiratory tract infection within the 4 weeks prior to Visit 1
- 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 4-week washout prior to Visit 0)
- Asthma-related ER visit within the previous 4 weeks of Visit 0
- History of ICU admission/intubation due to asthma in the past 1 year
- 3 or more asthma exacerbations requiring treatment with systemic corticosteroids for more than three days in the past year consistent with severe asthma
- Asthma exacerbation requiring systemic corticosteroids within the 4 weeks prior to Visit 0.
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- Chronic renal failure
- Positive urine cotinine or THC test on the day of the bronchoscopy visit
- 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
- Untreated sleep apnea
- Participant in an interventional drug study or use of investigative drugs within the past 30 days or plans to enroll in such a trial during the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Duke University (Asthma, Allergy and Airway Center)
Durham, North Carolina, 27705
Antoinette Santoro, MS, BSRT, 919-479-0731, maria.santoro@duke.edu
Catherine Foss, BS, RRT, (919) 613 - 7627, catherine.foss@duke.edu
About this study
Official title: Supplementing L-citrulline to Overweight Late Asthma oNset Phenotypes to Increase Airway L-arginine/ADMA Ratio and Improve Asthma Control
Patients with obese late onset (after childhood) asthma can have lower FeNO levels, yet be highly symptomatic and poorly responsive to inhaled steroids. This is a common asthma phenotype, particularly among females. This reduction of NO occurs through increased arginase activity and uncoupling of NO synthase (NOS), by accumulation of asymmetric di-methyl arginine (ADMA), which further lowers the L-arginine/ADMA ratio, preferentially promoting reactive oxygen species (ROS) formation and inflammation at the expense of NO. Indeed, in patients with obese late onset asthma, lower L-arginine/ADMA plasma ratios are associated with reduced FeNO, increased bronchial hyperreactivity, and greater asthma morbidity. In our pilot studies, the administration of L-citrulline, as an L-arginine donor, to patients with obese late onset asthma increased the L-arginine/ADMA ratio, FeNO levels, and improved asthma control and lung function. Therefore, the objectives of the protocol are to: a) determine the efficacy of L-citrulline, as an add-on treatment to improve the asthma control and lung function in obese late onset asthmatics; b) leverage the use of asthmatic and control cells to further understand obesity-related changes in epithelial airway NO metabolism, and how these changes relate to bronchoconstriction and lung function, c) determine airway epithelial changes in mitochondrial function and bioenergetics in obese late onset asthmatics and how these are modified by L-citrulline. To do this, 54 obese late onset asthmatics with suboptimal control will be blindly randomized, in a cross over study, comparing 15g/day of L-citrulline vs. placebo, in two 8-week treatment periods with a 6-week washout in between. The co-primary study outcomes are asthma control (ACQ, ACT) and FeNO, and secondary endpoints plasma L-arginine/ADMA, FEV1 and PC20 methacholine. Parallel to this study, a small study of 10 healthy obese controls will receive open label L-citrulline for 7 weeks to establish comparative reference values for the study aims. During the initial treatment phase, 50% of study participants will be randomly allocated to undergo pre and post L-citrulline treatment bronchoscopy to obtain BAL and airway epithelial cells. The research group proposing this study is highly experience in asthma clinical trials, implementation of cross over design studies, and in the use of research bronchoscopies.
- Being tested
- L-ctirulline, Matching Placebo
- Medical subject headings
- Asthma, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-ctirullineDrug
Also called L-citrulline
7 weeks of treatment with 15 g/day of orally administered (powder form mixed with water) L-citrulline
Matching 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 1 and 1a (if needed). Washout period of at least 5 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. Receives: Drug: L-ctirulline |
| 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 1 and 1a (if needed). Washout period of at least 5 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. Receives: Drug: Matching 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 by administering the questionnaires before, mid-way, and after during each treatment phase to see if there's a change in scores.
Measured: Through study completion, up to 32 weeks
Change in Asthma Control Test
To determine L-citrulline efficacy, reduction in questionnaires scores determined by administering the questionnaires before, mid-way, and after during each treatment phase to see if there's a change in scores.
Measured: Through study completion, up to 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2019
- Study start1 Oct 2021
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), Duke University
- Responsible party
- Sponsor
- Investigators
- Fernando Holguin, MD, MPH, Principal investigator, University of Colorado Denver- Anschutz Medical Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03885245
- Sponsor's protocol ID
- 19-0219
- Other IDs
- R01HL146542
- Acronym
- SANDIA
- Status last verified
- Jun 2025
- First submitted
- 6 Mar 2019
- Last updated
- 10 Jun 2025
- 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 10 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supplementing L-citrulline to Overweight Late Asthma oNset Phenotypes to Increase Airway L-arginine/ADMA Ratio and Improve Asthma Control
- ClinicalTrials.gov ID
- NCT03885245
- Acronym / sponsor ID
- SANDIA / 19-0219
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), Duke University
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 21 Mar 2019 (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.
Patients with obese late onset (after childhood) asthma can have lower FeNO levels, yet be highly symptomatic and poorly responsive to inhaled steroids. This is a common asthma phenotype, particularly among females. This reduction of NO occurs through increased arginase activity and uncoupling of NO synthase (NOS), by accumulation of asymmetric di-methyl arginine (ADMA), which further lowers the L-arginine/ADMA ratio, preferentially promoting reactive oxygen species (ROS) formation and inflammation at the expense of NO. Indeed, in patients with obese late onset asthma, lower L-arginine/ADMA plasma ratios are associated with reduced FeNO, increased bronchial hyperreactivity, and greater asthma morbidity. In our pilot studies, the administration of L-citrulline, as an L-arginine donor, to patients with obese late onset asthma increased the L-arginine/ADMA ratio, FeNO levels, and improved asthma control and lung function. Therefore, the objectives of the protocol are to: a) determine the efficacy of L-citrulline, as an add-on treatment to improve the asthma control and lung function in obese late onset asthmatics; b) leverage the use of asthmatic and control cells to further understand obesity-related changes in epithelial airway NO metabolism, and how these changes relate to bronchoconstriction and lung function, c) determine airway epithelial changes in mitochondrial function and bioenergetics in obese late onset asthmatics and how these are modified by L-citrulline. To do this, 54 obese late onset asthmatics with suboptimal control will be blindly randomized, in a cross over study, comparing 15g/day of L-citrulline vs. placebo, in two 8-week treatment periods with a 6-week washout in between. The co-primary study outcomes are asthma control (ACQ, ACT) and FeNO, and secondary endpoints plasma L-arginine/ADMA, FEV1 and PC20 methacholine. Parallel to this study, a small study of 10 healthy obese controls will receive open label L-citrulline for 7 weeks to establish comparative reference values for the study aims. During the initial treatment phase, 50% of study participants will be randomly allocated to undergo pre and post L-citrulline treatment bronchoscopy to obtain BAL and airway epithelial cells. The research group proposing this study is highly experience in asthma clinical trials, implementation of cross over design studies, and in the use of research bronchoscopies.
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-ctirullineL-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 1 and 1a (if needed). Washout period of at least 5 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. |
| Matching Placebo | Placebo comparator | Drug: Matching PlaceboAdministered in powder form that is mixed with water and taken orally, continuously, and daily for at least 7 weeks. Dispensed at Visits 1 and 1a (if needed). Washout period of at least 5 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adequate completion of informed consent process
- Male and female patients
- Physician diagnosis of asthma
- Able to perform reproducible spirometry according to ATS criteria
- Pre-bronchodilator FEV1 >/= 50% of predicted at Visit 0
Key exclusion criteria (13 listed)
- Respiratory tract infection within the 4 weeks prior to Visit 1
- 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 4-week washout prior to Visit 0)
- Asthma-related ER visit within the previous 4 weeks of Visit 0
- History of ICU admission/intubation due to asthma in the past 1 year
- 3 or more asthma exacerbations requiring treatment with systemic corticosteroids for more than three days in the past year consistent with severe asthma
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-ctirullineAlso: L-citrulline7 weeks of treatment with 15 g/day of orally administered (powder form mixed with water) L-citrulline | Drug | L-citrulline |
| Matching 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 32 weeks
to determine L-citrulline efficacy, reduction in questionnaire scores determined by administering the questionnaires before, mid-way, and after during each treatment phase to see if there's a change in scores.
Change in Asthma Control Test
Time frame: Through study completion, up to 32 weeks
To determine L-citrulline efficacy, reduction in questionnaires scores determined by administering the questionnaires before, mid-way, and after during each treatment phase to see if there's a change in scores.
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 10 Jun 2025.
- 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.
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-ctirulline in people with Asthma and Obesity, 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 13 inclusion and 13 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 10 Jun 2025. 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 Asthma Research (1 (844) 365-0852, asthmaresearch@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 32 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 10 Jun 2025.