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

Sponsor

Stefan Zielen (Other)

Overall Status

Unknown status

CT.gov ID

NCT04109534

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Allergic Asthma Allergy to House Dust Mite	Diagnostic Test: Bronchial allergen provocation (BAP) Diagnostic Test: Nasal provocation test (NPT) Diagnostic Test: Methacholine test Diagnostic Test: Peak nasal expiratory flow (PNIF)	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Placebo-controlled prospective studyPlacebo-controlled prospective study

Masking:

Double (Participant, Investigator)

Masking Description:

LCPUVAS and Placebo are provided in sealed bags

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Jun 30, 2020

Anticipated Study Completion Date :

Dec 30, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Decrase of exhaled NO (eNO) after BAP [4 weeks]
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.

Secondary Outcome Measures

Absolute levels eNO [4 weeks]
Comparison of absolute levels eNO (ppb)at end of treatment between groups
Magnitude of EAR [4 weeks]
Comparison of EAR (maximum decrease of FEV1) at end of treatment between groups
Magnitude of LAR [4 weeks]
Comparison of LAR (maximum decrease of FEV1 in %) at end of treatment between groups
FEV1 after BAP [4 weeks]
Comparison of FEV1 Levels 24 hours after BAP between groups
Comparison of methacholin levels [4 weeks]
Comparison of methacholin (mg) Levels 24 hours after BAP between groups
Asthma control test (ACT) [4 weeks]
Comparison of ACT score between Groups at end of treatment
Cumulative Salbutamol use [4 days]
Cumulative Salbutamol use in the last 4 days of treatment during repetitive BAP between groups
Lebel symptom score [4 weeks]
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.
Peak nasal expiratory flow [4 weeks]
Comparison of peak nasal expiratory flow (PNIF) after NPT between groups
Visual analog scala (VAS)-score after NPT [4 weeks]
Comparison of VAS (mm) after NPT between groups
Visual analog scala (VAS)-score for nasal symptoms [5 days]
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

Other Outcome Measures

Levels of LCPUFA [4 weeks]
Levels of LCPUFA will be measured before and after Supplementation between groups
Levels of triglyceride and cholesterin [4 weeks]
Levels of triglyceride and cholesterin will be measured before and after supplementation between groups
Levels of eosinophils [4 weeks]
Levels of eosinophils will be measured after supplementation and 24 hours after BAP between groups
micro RNAs [4 weeks]
Levels of micro RNAs will be measured before supplementation and before and 24 hours after BAP between groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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