NCT03885245RecruitingPhase 2
Supplementing L-citrulline to Overweight Late Asthma oNset Phenotypes
Supplementing L-citrulline to Overweight Late Asthma oNset Phenotypes to Increase Airway L-arginine/ADMA Ratio and Improve Asthma Control
Source: ClinicalTrials.gov · Last updated 10 Jun 2025 · Not updated for over 12 months - ask the site whether it is still open
Brief summary (registry, in English)
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.
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 60 (estimated)
- First submitted
- 6 Mar 2019
- Start date
- 1 Oct 2021
- Primary completion date
- 30 Dec 2025
- Lead sponsor
- University of Colorado, Denver
- NCT number
- NCT03885245
What you commit to
- Study type: Interventional · Phase 2
- Planned participants: 60
- From 1 Oct 2021 to the primary completion date, 30 Dec 2025
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- 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
- 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.
- Concomitant use of PDE5 drugs or oral mononitrates
- 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
Other illness
- History of ICU admission/intubation due to asthma in the past 1 year
- Chronic renal failure
- Intolerance or allergy to L-arginine or L-citrulline
Lab values
- Positive urine (or serum) pregnancy test at Visit 0 or at any time during the study
Other
- Positive urine cotinine or THC test on the day of the bronchoscopy visit
- Untreated sleep apnea
Who the study is looking for
- 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
- 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
Age in the registry: 18 years to 65 years · Sex: All · Accepts healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Duke University (Asthma, Allergy and Airway Center) Coordinator of this site? Confirm its status | Durham | United States | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.