Adding L-citrulline to treatment for adults with obesity-related late-onset asthma

Supplementing L-citrulline to Overweight Late Asthma oNset Phenotypes to Increase Airway L-arginine/ADMA Ratio and Improve Asthma Control

This trial will test whether daily L-citrulline supplements help adults with obesity and asthma that began after childhood who have low exhaled nitric oxide and poor symptom control.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Locations: 1 site (Durham, North Carolina)
• Trial ID: NCT03885245 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives eligible adults with obesity-related late-onset asthma either oral L-citrulline or a matching placebo and follows them for biochemical and clinical outcomes. The study targets participants who remain symptomatic on inhaled therapy and who have low FeNO, aiming to raise the L-arginine/ADMA ratio and NO availability. Outcomes include changes in the L-arginine/ADMA ratio, FeNO, spirometry, bronchial hyperreactivity, and asthma control scores. The design uses a placebo comparator to determine whether L-citrulline improves lung function and symptom control compared with placebo.

Who should consider this trial

Good fit: Ideal candidates are adults with physician-diagnosed asthma beginning at age 12 or older, BMI ≥30, FeNO ≤30 ppb, pre-bronchodilator FEV1 ≥50% predicted, on regular inhaled controller therapy (ICS ± LABA or LAMA), and with limited smoking history (≤10 pack-years).

Not a fit: Patients with childhood-onset asthma, BMI below 30, normal or high FeNO, recent respiratory infection or recent systemic steroids, significant recent ER visits for asthma, or heavy smoking history are unlikely to qualify or benefit from this intervention.

Why it matters

Potential benefit: If successful, L-citrulline could increase airway nitric oxide and improve lung function and asthma control in obese adults with late-onset asthma.

How similar studies have performed: Small pilot studies reported that L-citrulline increased the L-arginine/ADMA ratio, raised FeNO, and improved asthma control and lung function in this phenotype.

Eligibility criteria

Inclusion Criteria:

1. Adequate completion of informed consent process
2. Male and female patients
3. Physician diagnosis of asthma
4. Able to perform reproducible spirometry according to ATS criteria
5. Pre-bronchodilator FEV1 \>/= 50% of predicted at Visit 0
6. Confirmation of asthma
7. All racial/ethnic backgrounds may participate.
8. BMI \>/= 30
9. Regular treatment with ICS or ICS/LABA or LAMA combination medication for at least 1 month; participants can be on biologics.
10. Smoking history \</= 10 pack years and no smoking in the last 3 months
11. Age of asthma onset (diagnosis) \>/= 12 years
12. FeNO \</= 30 ppb
13. ACQ \>/= 0.50 or ACT \</=19

Exclusion Criteria:

1. Respiratory tract infection within the 4 weeks prior to Visit 1
2. 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)
3. Asthma-related ER visit within the previous 4 weeks of Visit 0
4. History of ICU admission/intubation due to asthma in the past 1 year
5. 3 or more asthma exacerbations requiring treatment with systemic corticosteroids for more than three days in the past year consistent with severe asthma
6. Asthma exacerbation requiring systemic corticosteroids within the 4 weeks prior to Visit 0.
7. Chronic renal failure
8. Positive urine cotinine or THC test on the day of the bronchoscopy visit
9. Positive urine (or serum) pregnancy test at Visit 0 or at any time during the study
10. Intolerance or allergy to L-arginine or L-citrulline
11. Concomitant use of PDE5 drugs or oral mononitrates
12. Untreated sleep apnea
13. 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 this trial is running

Durham, North Carolina

• Duke University (Asthma, Allergy and Airway Center) — Durham, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Fernando Holguin, MD, MPH — University of Colorado Denver- Anschutz Medical Campus
• Study coordinator: Asthma Research

Conditions Asthma; Obesity