NCT03885245 · University of Colorado, Denver
Supplementing L-citrulline to Overweight Late Asthma oNset Phenotypes
(SANDIA)
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
L-ctirulline
7 weeks of treatment with 15 g/day of orally administered (powder form mixed with water) L-citrulline
DRUG
Matching Placebo
7 weeks of treatment with orally administered matching placebo (to 15 g/day of L-citrulline)
Primary outcome measures
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
Exclusion criteria
- 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.
- 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
Where
- Durham, North Carolina
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), Duke University
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 10, 2025 · Source of record for eligibility and locations