The Effects of NOx and Conjugated Linoleic Acid on Asthmatics

NCT02433977 | Completed Phase 2 Results DMC

• 1 other identifier: PRO14110207
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the hypothesis that in obese asthmatics; treatment with NOx + CLA is well tolerated, safe and will increase eNO while reducing airway oxidative stress. Allied with this, the investigators will define whether supplementing with this bioactive mediator modifies the airway microbiome, and reduces airway inflammation.

Conditions

Asthma

Keywords

Asthma; Obesity; conjugated linolenic acid; nitrate; nitrite; nutritional supplements

Outcome Measures

Primary Outcomes (1)

• Change in Exhaled NO Before and After Treatment

  Determine how CLA and NOx affect airway NO bioavailability (exhaled NO)

  Before treatment at baseline and after treatment at 8 weeks

Secondary Outcomes (9)

• Biomarkers of Inflammation-bronchial Hyperresponsiveness Using PC20

  Before treatment at baseline and after treatment at 8 weeks

• Biomarkers of Inflammation- Concentration of Free CLA in Plasma

  Before treatment at baseline and after treatment at 8 weeks

• Number of Participants With an Increase in IL-6 and IL-1b Expression

  Before treatment at baseline and after treatment at 8 weeks

• Biomarkers of Inflammation-airway XO Activity

  Before treatment at baseline and after treatment at 8 weeks

• Biomarkers of Inflammation-15NO2-cLA

  Before treatment at baseline and after treatment at 8 weeks

Study Arms (1)

Conjugated Linolenic Acid + NOx

EXPERIMENTAL

This is a single arm study Conjugated Linolenic Acid (CLA)- daily oral dose 3 g/day Sodium Nitrate- Capsules for daily oral administration at the dose of 1 g (2 x 500 mg) Sodium Nitrite- Capsules for daily oral administration at the dose of 20 mg (2 x 10 mg)

Dietary Supplement: Conjugated Linolenic Acid; Drug: Sodium Nitrite; Drug: Sodium Nitrate

Interventions

Conjugated Linolenic Acid DIETARY_SUPPLEMENT

CLA is a polyunsaturated fatty acid Subjects will receive capsules for daily oral administration at the dose of 3 g/day

Also known as: conjugated linolenic acid (CLA)

Conjugated Linolenic Acid + NOx

Sodium Nitrite DRUG

Subjects will receive capsules for daily oral administration at the dose of 20 mg (2 x 10 mg)

Conjugated Linolenic Acid + NOx

Sodium Nitrate DRUG

Subjects will receive capsules for daily oral administration at the dose of 1g (2 x 500 mg)

Conjugated Linolenic Acid + NOx

Eligibility Criteria

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

You may qualify if:

• Adequate completion of informed consent process with written documentation
• Male and female patients, ≥ 18 - 65 yrs old
• Diagnosis of asthma: based on previous physician diagnosis and either baseline pre-bronchodilator FEV1 50% or greater predicted with a 12% or greater bronchodilator response to 4 puffs of albuterol or PC20 methacholine (16 mg) if no BD response.If the subject is not currently on an ICS/ ICS LABA, PC20 should be \< 8 mg, if no BD response. Spirometry results within the prior 24 months located in the subject's medical records can be used to determine eligibility, if available.
• All racial/ethnic backgrounds with a diagnosis of asthma for ≥6 months
• Smoking history ≤10 pack years and no smoking in the last year
• BMI ≥ 30
• If subject is on ICS or ICS/LABA therapy- 30 days on a stable dose (up to 1,000 mcg daily fluticasone equivalent)
• Asthma diagnosed at age 9 or later

You may not qualify if:

• Respiratory tract infection within the last 4 weeks
• Oral or systemic CS burst within the last 4 weeks
• Asthma-related hospitalization within the last 2 months
• Asthma-related ER visit within the previous 4 weeks
• Significant or uncontrolled concomitant medical illness including (but not limited to) heart disease, cancer, diabetes
• Chronic renal failure (creatinine \> 2.0) at screening (Associated with higher ADMA levels)
• Current statins use (statins lower ADMA levels), patients may stop and re-enroll after 2 weeks of stopping statins
• Positive pregnancy test
• Intolerance or allergy to the intervention drugs
• Current or recent (within 30 days) in an investigational treatment study.
• Unable or unlikely to complete study assessments or the study intervention (i.e. bronchoscopy) poses undue risk to patient in the opinion of the Investigator.
• Any kind of oral nitrates such as nitroglycerin or already taking supplements
• History of ICU admission/intubation due to asthma in the past year;
• More than three systemic corticosteroid requiring asthma exacerbations in the past year
• Systemic steroid dependent asthma (no daily oral steroids- short term therapy for asthma exacerbation is permitted)

Sponsors & Collaborators

• Gladwin, Mark, MD: lead

Study Sites (1)

The University of Pittsburgh Asthma Institute at UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Asthma; Obesity

Interventions

eleostearic acid; Sodium Nitrite; sodium nitrate

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)

Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Stacy Gelhaus Wendell
• Organization: University of Pittsburgh

gstacy@pitt.edu

412-648-1351

Study Officials

• Sally E Wenzel, MD

  The University of Pittsburgh Asthma Institute at UPMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 11, 2014
• First Posted: May 5, 2015
• Study Start: September 1, 2015
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: April 27, 2021
• Results First Posted: March 26, 2021

Record last verified: 2021-04

Locations

US (1)