L-Citrulline Supplementation Pilot Study for Overweight Late Onset Asthmatics

NCT01715844 | Completed Phase 1 DMC

• 1 other identifier: L-citrulline Asthma
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In people who develop asthma after the age of 12 and who are also overweigh, there can be an increased burden of asthma symptoms, more flare-ups, and poorly-controlled asthma when compared to normal weight asthmatics. Certain factors are more abundant in the blood of individuals who are obese. One such factor is derived from the metabolism of an amino acid found in your diet, which is known as L-arginine (Amino acids are most commonly known as the building blocks of proteins, the same as the proteins found in food). This factor is called asymmetric dimethylarginine or ADMA. The balance of L-arginine to ADMA may be important to the health of subjects with asthma. The balance between L-arginine and ADMA plays an important role in producing nitric oxide (NO) in the airways. NO is normally produced in the lung and plays a major role in maintaining airways open and functioning normally. Our research has shown that in subjects with asthma who are overweight and developed asthma later in life, the combination of low L-arginine and high ADMA, may lead to lower NO levels. We are asking participants in this study to take L-citrulline, which is converted to L-arginine by your body, as a supplement for a period of one week. We anticipate that L-citrulline will restore NO levels in the airways, by increasing the ratio of L-arginine to ADMA

Conditions

Asthma

Keywords

L-citrulline; ADMA; Asthma; Obesity

Outcome Measures

Primary Outcomes (1)

• Exhaled nitric oxide

  Patients will be randomized to 1 week of 3 g of L-citrulline/day vs matching placebo, The outcome is the pre to post intervention change in exhaled NO

  1 week

Secondary Outcomes (1)

• Sputum and plasma L-arginine/ADMA levels

  1 week

Study Arms (2)

L-citrulline

ACTIVE COMPARATOR

3-gr/day of L-citrulline effervescent powder mix

Dietary Supplement: L-citrulline

Placebo

PLACEBO COMPARATOR

3 gr of Placebo/day matching L-citrulline effervescent powder

Dietary Supplement: L-citrulline

Interventions

L-citrulline DIETARY_SUPPLEMENT

Patients will take 3-gr of L-citrulline/day for 7 days

Also known as: L-citrulline 3 gr efervescent powder

L-citrulline; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients, 18-75 yrs old, from all racial/ethnic backgrounds
• Diagnosis of asthma for \>1 yr
• BMI ≥ 30
• Baseline pre-bronchodilator FEV1 between 60 and 90% predicted with a 12% or greater bronchodilator response to 4 puffs of albuterol
• Smoking history \<20 pack years and no smoking in the last year
• Able to identify age of asthma onset

You may not qualify if:

• Respiratory tract infection within the last 4 weeks;
• Oral CS burst within the last 4 weeks or regular systemic CS use
• Hospitalization within the last 3 months
• ER visit within the 4 weeks
• Significant or uncontrolled concomitant medical illness including (but not limited to) heart disease, cancer, diabetes
• Current smoking or within the previous 12 months
• Current use of statins for the past 30 days (Statins lower ADMA levels)
• Pregnancy
• Intolerance or allergy to L-arginine or L-citrulline
• Phosphodiesterase inhibitors
• Taking oral nitrates

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

Asthma Institute, University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Holguin F, Grasemann H, Sharma S, Winnica D, Wasil K, Smith V, Cruse MH, Perez N, Coleman E, Scialla TJ, Que LG. L-Citrulline increases nitric oxide and improves control in obese asthmatics. JCI Insight. 2019 Dec 19;4(24):e131733. doi: 10.1172/jci.insight.131733.

  PMID: 31714895 DERIVED

MeSH Terms

Conditions

Asthma; Obesity

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Fernando Holguin, MD MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 29, 2012
• Study Start: September 7, 2013
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2017
• Last Updated: July 2, 2017

Record last verified: 2017-06

Locations

US (1)