Asthma L-Citrulline Pilot Study (ALPS)

This study will evaluate whether treatment with L-citrulline, which is an amino acid found in some foods, can increase levels of L-arginine and thereby restore the concentration of nitric oxide (NO) in the airways.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Dietary supplement: L-Citrulline

Detailed Description

Research has shown that some obese asthmatics have a metabolic imbalance in which L-arginine levels are reduced. L-arginine is an amino acid that is used to make NO, a gas that is normally made in the bronchi and ensures that the lungs function properly. 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-label treatment with 15g/day of L-citrulline for two weeks. Study participants will be asked to do lung function testing and donate blood before and after taking the supplement. L-citrulline is safe and well tolerated and has been used at much higher doses without significant side effects.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adequate completion of informed consent process with written documentation
• Male and female patients, 18 - 70 years old, inclusive
• Physician diagnosis of asthma (for medical records, ICD 10 coding for physician's diagnosis)
• All racial/ethnic backgrounds may participate
• BMI ≥ 30
• Treatment of controller asthma medication(s) ≥ 4 weeks
• Smoking history ≤10 pack years and no smoking in the last year
• V1 eNO ≤ 30ppb (may be repeated 3x during visit; lowest ppb will be kept)

Exclusion Criteria:

• Respiratory tract infection within the 4 weeks prior to the study (may re-enroll after 4 weeks).
• Oral or systemic corticosteroid burst (for any indication) within the 4 weeks
• One-time doses, such as intra-articular injections into a shoulder or knee joint, require a 2-week washout.
• Asthma-related ER visit within the previous 4 weeks of Visit 1

• Significant concomitant medical illness, including (but not limited to)

  • Heart disease
  • Cancer
  • Uncontrolled diabetes,
• Chronic renal failure (creatinine > 2.0) at Visit 1 (Associated with higher ADMA levels)
• Untreated sleep apnea
• Other chronic lung/respiratory diseases (COPD, IPF, etc.)
• High dose inhaled steroids (> 1000 mcg/day of Fluticasone or equivalent)
• Current statin use (statins lower ADMA levels); patients may stop statins with approval from their primary physician and enroll after a 6-week washout
• Positive urine pregnancy test at Visit 1 or at any time during the study
• Intolerance or allergy to L-arginine or L-citrulline
• Concomitant use of PDE5 drugs or oral mononitrates
• Participation in an intervention study, use of investigative drugs within the past 30 days or plans to enroll in such a trial during the study
• Unable or unlikely to complete study assessments in the opinion of the Investigator
• Study intervention poses undue risk to patient in the opinion of the Investigator
• Breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: L-Citrulline; 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-label treatment with 15g/day of L-citrulline for two weeks. Study participants will be asked to do lung function testing and donate blood before and after taking the supplement. L-citrulline is safe and well tolerated and has been used at much higher doses without significant side effects.

Dietary supplement: L-Citrulline; The purpose of this study is to see if citrulline supplementation will restore NO levels and lung function in subjects with asthma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Exhaled Nitric Oxide (eNO)	Change in eNO levels before and after treatment with open label L-citrulline at 15g/day	2 weeks or 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma L-arginine/ADMA Ratio	Change in L-arginine/ADMA before and after 2 weeks of L-citrulline at 15g/day	2 weeks or 14 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Asthma Control Score	Change in asthma control scores (ACQ)	2 weeks or 14 days

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Fernando Holguin, MD, MPH, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2017
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Obesity; L-citrulline
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 16-2041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Sharing de-identified data with co-investigators approved by the IRB and Duke University

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No