L-citrulline for Asthma

(SANDIA Trial)

Overseen By Asthma Research

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must be taking: ICS, ICS/LABA, LAMA

Must not be taking: PDE5, Mononitrates

Disqualifiers: Chronic renal failure, Untreated sleep apnea, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether L-citrulline, a supplement, can improve asthma control and lung function in individuals with a specific type of asthma that begins after childhood and is associated with obesity. The research team aims to determine if L-citrulline can enhance certain molecules that aid breathing and reduce inflammation. Participants will receive either L-citrulline or a placebo (a harmless substance resembling the treatment) in different phases to compare results. This trial suits individuals who have had asthma since at least age 12, have a BMI of 30 or above, and continue to struggle with asthma control despite regular inhaler use. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify that you need to stop taking your current medications. However, you must have been on regular treatment with certain asthma medications for at least one month, and you cannot use certain drugs like PDE5 inhibitors or oral mononitrates during the study.

Is there any evidence suggesting that L-citrulline is likely to be safe for humans?

Research has shown that L-citrulline is safe and generally well-tolerated. In past studies, even at much higher doses, it did not cause significant side effects. This treatment may improve asthma symptoms and lung function, particularly in individuals with asthma who are also obese. L-citrulline boosts nitric oxide levels, which can open airways and ease breathing. Participants have not reported any major negative effects, suggesting it could be a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Unlike the standard asthma treatments, which typically include inhaled corticosteroids and bronchodilators, L-citrulline offers a unique approach by potentially enhancing nitric oxide production in the body. Nitric oxide can help widen blood vessels and improve blood flow, which might reduce inflammation and improve respiratory function in asthma patients. Researchers are excited about L-citrulline because it is a naturally occurring amino acid, which could mean fewer side effects and a more holistic treatment option compared to conventional medications.

What evidence suggests that L-citrulline might be an effective treatment for asthma?

Research shows that L-citrulline can help improve asthma symptoms, particularly in individuals with obesity-related asthma. Past studies found that L-citrulline increases FeNO levels, indicating airway inflammation, and enhances overall asthma control. Participants in this trial will receive L-citrulline, which has improved lung function, demonstrated by larger increases in FEV1, a measure of air exhaled in one second. These benefits were more noticeable in individuals with low or normal FeNO levels. The treatment boosts nitric oxide production, reducing airway tightening and inflammation. ^{1 2 4 6 7}

Who Is on the Research Team?

Fernando Holguin, MD, MPH

Principal Investigator

University of Colorado Denver- Anschutz Medical Campus

Are You a Good Fit for This Trial?

This trial is for adults with asthma that started after childhood, who are obese (BMI >= 30), and have a history of poor response to inhaled steroids. They should be on regular asthma medication but not have had an exacerbation or used systemic corticosteroids in the last month. Smokers or those with recent lung infections aren't eligible.

Inclusion Criteria

All racial/ethnic backgrounds may participate

You have a higher than or equal to 0.50 ACQ score or a less than or equal to 19 ACT score.

I have been on regular asthma or COPD medication for at least a month.

Exclusion Criteria

I was admitted to the ICU or needed a breathing tube for asthma in the last year.

I visited the ER for asthma within the last 4 weeks.

I have not had a respiratory infection in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive 15g/day of L-citrulline or placebo for 8 weeks

8 weeks

Visits at start, mid-way, and end of treatment

Washout

Participants undergo a washout period between treatment phases

6 weeks

Treatment Period 2

Participants crossover to receive the alternate treatment (L-citrulline or placebo) for 8 weeks

8 weeks

Visits at start, mid-way, and end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• L-citrulline

Trial Overview The study tests if L-citrulline improves asthma control and lung function in obese adults with late-onset asthma. Participants will take either L-citrulline or a placebo over two 8-week periods, separated by a washout period, to compare effects on their condition.

How Is the Trial Designed?

Group I: L-citrulline Experimental Treatment 1 Intervention

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.

Group II: Matching Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6975256/

L-Citrulline increases nitric oxide and improves control in ... Short-term L-citrulline treatment improved asthma control and FeNO levels in obese asthmatics with low or normal FeNO. Larger FEV1 increments were observed in ...

2. insight.jci.org insight.jci.org/articles/view/137777

l-Arginine supplementation in severe asthma A recent clinical trial of l-citrulline supplementation in individuals with asthma found that l-citrulline increased FeNO and modestly improved forced ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02943161

NCT02943161 | Asthma L-Citrulline Pilot Study In this pilot study subjects with asthma that have an increased body mass index compatible with being obese, will be invited to participate in a short open- ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299906007795

Role of the l-citrulline/l-arginine cycle in iNANC nerve ... Remarkably, the impaired iNANC relaxation after the early asthmatic reaction was restored by l-citrulline.

5. researchstudies.cuanschutz.edu researchstudies.cuanschutz.edu/Study/19-0219

Find a Research Study 1. Determine if L-citrulline supplementation improves asthma control and increases FeNO (co-primary outcomes). Secondary outcomes will include changes in plasma ...

6. bmjopenrespres.bmj.com bmjopenrespres.bmj.com/content/10/1/e001683

Phenotypic characteristics of asthma and morbidity are ... L-citrulline supplementation can improve asthma control and lung function while augmenting exhaled nitric oxide (NO). From these and other ...

7. respiratory-research.biomedcentral.com respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-13-68

L-citrulline supplementation reverses the impaired airway ... L-citrulline has been shown to restore impaired relaxation of airways after early asthmatic reaction [27].