Effect of a Dietary Fatty Acid Supplementation on Symptoms and Bronchial Inflammation in Patients With Asthma (LCPUFA)

Investigation of the Effect of a Dietary Fatty Acid Supplementation on Symptoms and Bronchial Inflammation in Patients With Asthma and House Dust Mite Allergy After Repeated Allergen Challenge

The proposed study will investigate the effect of a polyunsaturated fatty acid / lipid mixture (LCPUFAs) on the clinical symptoms, bronchial inflammation and lung function in allergic asthma in a bronchial allergen provocation (BAP) model. For this purpose, patients with stable episodic asthma and dust mite allergy will underwent BAP before and after supplementation with LCPUFAs. The clinical symptoms, bronchial inflammation, exhaled NO increase and lung function decline (FEV1) will be analyzed.

Study Overview

• Status: Unknown
• Conditions: Allergic Asthma; Allergy to House Dust Mite
• Intervention / Treatment: Diagnostic test: Bronchial allergen provocation (BAP); Diagnostic test: Nasal provocation test (NPT); Diagnostic test: Methacholine test; Diagnostic test: Peak nasal expiratory flow (PNIF)

Detailed Description

Asthma is a chronic lung disease, which is characterized by recurrent obstruction, a hypersensitivity and a chronic inflammation of the airway. It is known that LCPUVAs could reduce the production of inflammatory mediators. In addition, LCPUVAs can improve pulmonary function, with a concurrent reduction in bronchodilator use in patients with asthma. Subjects suffering from episodic asthma and house dust mite (HDM) allergy usually have a normal lung function testing at rest and show a decrease in lung function when they are exposed to HDM. Bronchial allergen provocation models are well established in asthma research and allow the evaluation of anti-allergic and anti-asthmatic agents in relatively small sample sizes. In a previous study the investigators could show, that LCPUVAs could reduce exhaled NO after repeated BAP with HDM.

In this study the investigators will investigate the protective effect of LCPUVAs in a repeated BAP model. Clinical symptoms (nasal and bronchial), exhaled NO, decrease in lung function the early asthmatic reaction (EAR), the late asthmatic reaction (LAR) and blood parameters (Triglyceride and Cholesterin and mircro RNAs) will be measured before and after LCPUVA supplementation.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Recruiting
      • Klinik für Kinder- und Jugendmedizin Universitätsklinikum
      • Contact: Stefan Zielen, Professor; Phone Number: 83063 +49 696301; Email: Stefan.zielen@kgu.de
      • Contact: Paola JE Gnago, MD; Phone Number: +4915780560152; Email: Paola.Gnago@kgu.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent

  • Patients: aged ≥18 and 45 years
  • known allergen induced asthma and HDM-Allergy
  • basic lung function FVC ≥ 80%, FEV1 ≥ 75%
  • decrease in FEV1 after BAP ≥ 20%
  • 30% increase of NO after BAP

Exclusion Criteria:

• lung function Forced vital capacity (FVC) <80% and Forced expiratory volume in 1 second (FEV1) <75%
• chronic diseases or infections (e.g. HIV, Tbc)
• pregnancy
• systemic corticosteroid-treatment
• inhalative corticosteroid therapy or leukotriene antagonists
• alcohol, substance or drug abuse
• current smokers
• inability to capture extend and consequences of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo comparator 20 patients aged 18-45 years with a diagnosis of HDM induced allergic asthma and an increase of exhaled NO of 30% after BAP will be randomized to the Placebo Comparator	Diagnostic test: Bronchial allergen provocation (BAP); Nebulized Dermatophagoides farina administered at following doses: 10AE, 20 AE, 40 AE, 80 160 AE, etc… until the FEV1 decreases 20% below the initial FEV1-value; Diagnostic test: Nasal provocation test (NPT); Dermatophagoides farina will be administered in both nostrils; Diagnostic test: Methacholine test; Nebulized metacholine will be administered at following doses: 0,01mg, 0,1mg, 0,4mg, 0,8mg und 1,6mg until the FEV1 decreases 20% below the initial FEV1-value; Diagnostic test: Peak nasal expiratory flow (PNIF); Comparison of peak nasal expiratory flow (PNIF) after NPT between groups
Active Comparator: Verum; PUFAS: 2640 mg of middle-chain and polyunsaturated fatty acids 20 patients aged 18-45 years with a diagnosis of HDM induced allergic asthma and an increase of exhaled NO of 30% after BAP will be randomized to the Active Comparator	Diagnostic test: Bronchial allergen provocation (BAP); Nebulized Dermatophagoides farina administered at following doses: 10AE, 20 AE, 40 AE, 80 160 AE, etc… until the FEV1 decreases 20% below the initial FEV1-value; Diagnostic test: Nasal provocation test (NPT); Dermatophagoides farina will be administered in both nostrils; Diagnostic test: Methacholine test; Nebulized metacholine will be administered at following doses: 0,01mg, 0,1mg, 0,4mg, 0,8mg und 1,6mg until the FEV1 decreases 20% below the initial FEV1-value; Diagnostic test: Peak nasal expiratory flow (PNIF); Comparison of peak nasal expiratory flow (PNIF) after NPT between groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrase of exhaled NO (eNO) after BAP	After BAP with HDM the decrease of eNO will be compared between placebo and active comparator. A relevant decrease is defined as a drop of 30% of exhaled NO.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute levels eNO	Comparison of absolute levels eNO (ppb)at end of treatment between groups	4 weeks
Magnitude of EAR	Comparison of EAR (maximum decrease of FEV1) at end of treatment between groups	4 weeks
Magnitude of LAR	Comparison of LAR (maximum decrease of FEV1 in %) at end of treatment between groups	4 weeks
FEV1 after BAP	Comparison of FEV1 Levels 24 hours after BAP between groups	4 weeks
Comparison of methacholin levels	Comparison of methacholin (mg) Levels 24 hours after BAP between groups	4 weeks
Asthma control test (ACT)	Comparison of ACT score between Groups at end of treatment	4 weeks
Cumulative Salbutamol use	Cumulative Salbutamol use in the last 4 days of treatment during repetitive BAP between groups	4 days
Lebel symptom score	Comparison of Lebel symptom score after nasal provocation test (NPT), before and after supplementation between groups. A lebel score of 0-4 is negative, a lebel score >5 positive, the maximum result is 12.	4 weeks
Peak nasal expiratory flow	Comparison of peak nasal expiratory flow (PNIF) after NPT between groups	4 weeks
Visual analog scala (VAS)-score after NPT	Comparison of VAS (mm) after NPT between groups	4 weeks
Visual analog scala (VAS)-score for nasal symptoms	Comparison of cumulative VAS-score for 4 nasal symptoms (Total mm each symptom) in the last 5 days of treatment during repetitive BAP between groups	5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of LCPUFA	Levels of LCPUFA will be measured before and after Supplementation between groups	4 weeks
Levels of triglyceride and cholesterin	Levels of triglyceride and cholesterin will be measured before and after supplementation between groups	4 weeks
Levels of eosinophils	Levels of eosinophils will be measured after supplementation and 24 hours after BAP between groups	4 weeks
micro RNAs	Levels of micro RNAs will be measured before supplementation and before and 24 hours after BAP between groups	4 weeks

Collaborators and Investigators

• Sponsor: Stefan Zielen
• Investigators: Principal Investigator: Stefan Zielen, Professor, Klinik für Kinder- und Jugendmedizin Universitätsklinikum

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 29, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: allergic asthma,; house dust mite allergy; bronchial allergen provocation; LCPUFAs
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Inflammation; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Cholinergic Agonists; Respiratory System Agents; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Methacholine Chloride
• Other Study ID Numbers: 19-263

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data will be provided of the investigated cohort
• IPD Sharing Time Frame: After end of study anticipated June 2020
• IPD Sharing Access Criteria: The data will be available after the end of study and successful publication of the results (anticipated June 2021 for 10 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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