Dietary Intervention in Food Allergy (AC18/00031)

April 22, 2024 updated by: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Dietary Intervention in Food Allergy: Microbiome, Epigenetic and Metabolomic Interactions

The goal of this randomized double-blind placebo-controlled clinical study is to determine whether the dietary intervention with pectins leads to food immunomodulation in non-specific lipid transfer proteins (nsLTP) allergic patients. The main question it aims to answer is if the microbiome is a target of intervention against food allergy through the use of prebiotics such as pectins.

Participants will be enrolled to receive a two-month dietary intervention with either two different pectins (citrus or apple pectin) or placebo. Increase in oral tolerance to the peach nsLTP will be measured through a double-blind placebo-controlled food challenge (DBPCFC). Microbiome, proteomic and metabolomic studies will also be performed in blood and stool samples.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

DIFAMEM is an original integrative project that aims to use the potential of a pectin-enriched diet to treat food allergy, comprehensively addressing its effects on the epigenome and microbiome, metabolomic modifications and immune modulation. DIFAMEM has been approved by the Regulatory Authorities and Ethics Research Committee of Malaga.

In recent years the microbiome has gained attention as a target of intervention against food allergy, e.g. through the use of prebiotics, which are non-digestible food components that stimulate the growth and activity of certain microorganisms. There is currently great interest in the potential of plant-derived dietary fiber as a protective component against allergies, based on promising results which have been obtained in asthma models. Dietary fibers such as pectin can alter the gut microbiota and lead to increased local and systemic concentrations of gut microbiota-derived short chain fatty acids (SCFAs). SCFAs, including acetate, propionate, and butyrate, can promote the generation of peripheral regulatory T cells by epigenetic modulation, and suppress the inflammatory function of dendritic cells (DC) by transcriptional modulation. It is probable that additional metabolites also play an important role in these processes. Therefore, metabolomics applied in an untargeted approach for food allergy is an attractive option for the discovery of novel metabolites. This technology has been used to show a relationship between the beneficial effects upon using prebiotics and changes in faecal metabolites.

Pectin is a polysaccharide that occurs naturally in fruits, mainly in the peel and core. It has been recently reported that a diet supplemented with pectin alters the ratio of Firmicutes to Bacteroidetes in gut and lung microbiota, increases the concentrations of SCFAs in faeces and sera, and reduces the development of airway inflammation by suppressing DC function via engagement of GPR41 (free fatty acid receptor 3, FFAR3). Notably, natural apple pectin has been shown to have an immunomodulatory effect on allergies, although the mechanisms still need to be elucidated. The dominant component of pectin is a linear chain of galacturonic acid (GalA) in which a proportion of the carboxyl acid groups are present as methylesters. The ratio of esterified GalA groups to total GalA groups is termed the degree of esterification (DE). Two types of pectin exist: high methoxy pectin (HMP) with DE >50% or low methoxy pectin (LMP) with DE <50%. The majority of natural pectin is HMP, whereas LMP is more common in processed foods. Both HMP and LMP appear to possess immunomodulatory effects and increase SCFA levels in treated mice. LMP is more efficiently fermented by the microbiota in the ileum whereas HMP is mainly fermented in the proximal colon. These data suggest that the different types of pectin may exert their immunomodulatory effects through different mechanisms, however little is known about the different types of pectin in relation to food allergy.

Food allergy has dramatically increased in prevalence by over 50% during the last decade and is estimated to affect 5% of adults and 8% of children. Fruits are the most frequent triggers in adolescents and adults worldwide. The Rosaceae family contains the most often involved fruits, with non-specific lipid transfer proteins (nsLTPs) the primary sensitizers, such as the major peach allergen Pru p 3. NsLTPs are panallergens associated with sensitization to multiple taxonomically unrelated plant-derived foods. They are very stable and can cause a complex clinical pattern known as LTP-syndrome, which includes life-threatening reactions such as anaphylaxis. This syndrome, even in milder forms, can greatly impact quality of life and causes high socio-economic cost.

The DIFAMEM study is based on the hypothesis that dietary intervention will lead to beneficial effects for food allergic patients, using a natural food constituent with prebiotic properties like pectins. Such an intervention would be safer than specific allergen immunotherapy, avoiding allergic side effects. Studying the mechanisms of this intervention by modern innovative omics technologies will allow us to further optimize the approach in a targeted fashion.

Participants with a confirmed nsLTP allergy from the Allergy Unit of Hospital Regional Universitario de Málaga will be enrolled after informed consent obtention to receive a dietary intervention with two different pectins (citrus low DE or apple high DE) or placebo. DBPCFC with known quantities of Pru p 3 will be performed before and after the dietary intervention to determine improvement in nsLTP oral tolerance. Blood and stool samples will also be collected before and after the intervention to analyze the effects on the epigenome and microbiome, metabolomic modifications and immune modulation.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Malaga, Spain
        • Hospital Regional Universitario de Málaga

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults with a clear clinical history of food allergy after eating peach (oral allergy syndrome and/or systemic symptoms)
  • Sensitization to Pru p 3 by positive skin prick test (SPT wheal area >7 mm2) and specific IgE (sIgE >0.35 kU/L)
  • Positive DBPCFC (Sampson 2012) with peach juice
  • Signed informed consent

Exclusion Criteria:

  • Any clinical condition contraindicating performance of DBPCFC
  • A negative result in the DBPCFC
  • Lactation
  • Active infections
  • Acute/chronic inflammatory, autoimmune, and/or oncological diseases
  • Diabetes
  • Obesity
  • Severe immunodeficiency
  • Metabolic syndrome
  • Alcohol disorder
  • Mental illness
  • Increased liver parameters and any liver disease
  • Smoking habit
  • Enzymatic deficiency
  • Being vegetarian and taking vitamin supplements, probiotics, prebiotics, antibiotics, metformin, statins, proton pump inhibitors, or corticosteroids in the last three months, and immunomodulators and/or immunotherapy in the last five years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Citrus pectin dietary intervention group
This group will orally take 10 g of citrus pectin with low DE (7,3%) + 5 g of maltodextrin twice a day during two months.
Dietary supplement: Citrus pectin with low DE
Dietary intervention with citrus pectin with low DE. Participants will orally take the supplement twice a day, after dissolving it in 100ml of water, for 2 months.
Other Names:
  • Classic pectin
Experimental: Apple pectin intervention group
This group will orally take 10 g of apple pectin with high DE (57%) + 5 g of maltodextrin twice a day during two months.
Dietary supplement: Apple pectin with high DE
Dietary intervention with apple pectin with high DE. Participants will orally take the supplement twice a day, after dissolving it in 100ml of water, for 2 months.
Other Names:
  • Herbapekt
Placebo Comparator: Placebo group
This group will orally take placebo (5 g of maltodextrin) twice a day during two months.
Dietary supplement: Placebo
Participants will orally take the placebo (maltodextrin) twice a day, after dissolving it in 100ml of water, for 2 months. Maltodextrin is highly digestible and in small amounts will have limited impact on gut microbiome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical efficacy of pectin dietary intervention in nsLTP allergic patients
Time Frame: 16 months
Clinical efficacy is defined as a significant increase in Pru p 3 (μg) tolerance, measured through DBPCFC performed before and after the pectin intervention, compared to the Placebo.
16 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Pru p 3 (nsLTP of peach) specific IgE production induced by pectin intervention
Time Frame: 18 months
Results will be expressed as kUA/L.
18 months
Pru p 3-specific maturational changes of dendritics cells induced by pectin intervention
Time Frame: 18 months
Results will be expressed as maturation index (MI).
18 months
Pru p 3-specific proliferative response of different lymphocytes cell subpopulations after pectin intervention
Time Frame: 18 months
The specific proliferation responses of different lymphocytes subpopulations will be measured: Th1, Th2, Th9, and Plasma-cells/IgE+, T regulatory cells (Treg), Treg/IL10+ and B regulatory cells/ IL10+. The results will be expressed as fold change of proliferation index (PI).
18 months
Changes in Pru p 3-specific basophil activation induced by pectin intervention
Time Frame: 18 months
Results will be presented as the percentage of activated basophils (CD63+CD203c+CCR3+) and basophil allergen threshold sensitivity (CD-Sens).
18 months
Changes induced in the taxonomic diversity of gut microbiota
Time Frame: 18 months
STAMP (Statistical Analysis of Metagenomic Profiles, v2.1.3) will be used to identify particular taxa that significantly differ in abundance (%) between groups.
18 months
Changes in feaces metabolome induced by pectin dietary intervention
Time Frame: 18 months
Metabolomic profile from feaces samples will be analysed using a combination of untargeted mass spectrometry techniques: liquid chromatography-mass spectrometry (LC-ESI-QTOF-MS) and capillary electrophoresis-mass spectrometry (CE-TOF-MS). Results will be expressed as µg/g.
18 months
Changes in serum metabolome induced by the pectin dietary intervention
Time Frame: 18 months
Metabolomic profile from serum samples will be analysed by a combination of liquid chromatography-mass spectrometry (LC-MS) and gas chromatography coupled to mass spectrometry (GC-MS). Results will be expressed as µg/mL.
18 months
Epigenomic changes induced by the pectin dietary intervention
Time Frame: 18 months
Analysis of the methylome will be performed by EPIC array (Illumina).
18 months
Pectin safety profile
Time Frame: 16 months
Analysis of the frequency of adverse events induced by pectin supplement. Determination of liver function parameters, appearance of allergic reactions and/or gastrointestinal symptoms.
16 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Investigators

  • Principal Investigator: María José Torres, MD, PhD, Allergy Clinical Unit, Hospital Regional Universitario de Málaga, Málaga, Spain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Actual)

January 31, 2023

Study Completion (Actual)

June 30, 2023

Study Registration Dates

First Submitted

April 4, 2024

First Submitted That Met QC Criteria

April 22, 2024

First Posted (Actual)

April 26, 2024

Study Record Updates

Last Update Posted (Actual)

April 26, 2024

Last Update Submitted That Met QC Criteria

April 22, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC18/00031

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

DIFAMEM study will adhere to FAIR data principles (Findable, Accessible, Interoperable, and Reusable data). We will make all data available as appropriate, including a detailed description of protocols and analysis pipelines, to ensure that results can be reproduced, and to facilitate further analysis and development of this work by other groups. We will make the data preserved accessible, and used in accordance with scientific norms of fair attribution and use.

IPD Sharing Time Frame

Data will be released upon publication and preserved for a minimun of 10 years.

IPD Sharing Access Criteria

Free access.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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