Clinical trial NCT05208528: Effect of the Probiotic ES1 and Its Inactivated Form (HT-ES1) Over Symptomatology Asociated With Allergic Rhinitis
Official title: Effect of the Probiotic Bifidobacterium Longum ES1 and Its Inactivated Form by Heat (HT-Bifidobacterium Longum ES1) Over Symptomatology Asociated With Allergic Rhinitis. Parallel, Randomized, Controled, and Double-Blind Intervention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Allergic Rhinitis
Keywords: Probiotics
Intestinal Microbiota
Immune system
Inflammation
Postbiotics
Lead sponsor: Fundació Eurecat
Sponsor class: OTHER
Collaborators: name: ADM-BIOPOLIS S.L.
First posted: 2022-01-26
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Allergic rhinitis (AR) is a health problem characterised by an inflammatory reaction in the nasal mucosa mediated by immunoglobulin (Ig) E and resulting from exposure to environmental allergens, such as pollen and dust mites.

AR symptoms can significantly affect the quality of life of patients suffering from AR, causing substantial direct health care costs and indirect costs due to absenteeism from work.

The effects of pharmacological treatments are not always fully effective and have adverse effects, resulting in a significant proportion of AR patients continuing to experience symptoms or being dissatisfied.

Considering the relationship between AR and intestinal microbiota (IM), the use of probiotics, live microorganisms that, when consumed in adequate amounts, confer beneficial effects on the host, emerges as a potential strategy to prevent or treat certain allergies. There are different mechanisms of action by which probiotics may exert their effects on the treatment or prevention of allergies through modulation of the immune system and stimulation of tolerance. Probiotics promote a change in IM. In addition, probiotics stimulate gut-associated lymphoid tissue, modulating inflammation and immune reactions present in AR, promoting a more favourable profile by increasing the production of the modulatory cytokines IL-10 and TGFβ by Treg cells. Probiotics can restore the Th1:Th2 balance by inducing Th1 responses through the production of IL-12 and interferon (IFN)-γ, or by suppressing Th2 responses through the depletion of IL-4. In addition, probiotics may exert immunomodulatory effects through stimulating mucosal IgA production.

The hypothesis of the present study is that supplementation with the probiotic Bifidobacterium longum ES1 and/or with the heat treated version of ES1 will decrease the symptomatology associated with AR and improve the quality of life of individuals by modulating IM and potentiating Treg cells and the Th1 response.

The main objective of the present study is to determine the effects of supplementation with the probiotic Bifidobacterium longum ES1 and the heat treated version of ES1 (HT-ES1) on the symptoms associated with AR.

The secondary objectives of the study are to determine the effects of the treatments over: 1) Quality of life; 2) Blood immunological markers (IFN-γ, IL-12, IL-10, TGF-β, IgE, IL-4, IL-13, IL-19 and IL-8); 3) Faecal immunological marker IgA; 4)Faecal microbiota composition.

Detailed description: Parallel, randomized, placebo-controlled, and double-blind intervention trial.

75 participants (25 in each group), men and women, aged between 18 and 60 years, with moderate-severe persistent AR symptoms and dust mite allergy.

The 75 study participants will be randomly divided into three groups depending on whether they receive supplementation with the probiotic Bifidobacterium longum ES1, supplementation with the heat treated version of ES1 (HT-ES1) or placebo during the 2-month study period. After the treatment period the volunteers will be followed up for one month.

During the study, patients will be able to continue using conventional drug treatment for AR, including oral and local antihistamines, oral and intranasal corticosteroids, and intranasal decongestants.

Intervention products are the probiotic Bifidobacterium longum ES1 (ES1), the heat treated version of ES1 (HT-ES1) and a placebo (maltodextrin). The delivery format of the products to the volunteers will be in capsules.

The total duration of the study will be of 92 days (13 weeks).

Each participant will perform 4 visits. The study visits will be the following:

* a pre-selection visit to check inclusion/exclusion criteria (V0; day 1, week 1) and, in case of meeting the criteria,
* a study start visit (V1; day 8 +/-3 days; week 2),
* a final study visit (V2; day 64 +/- 3 days; week 10),
* a study follow-up visit (V3; day 92 +/- 3 days; week 14).

At visits V0, V1, V2 and V3 the use of any medications, including over the counter, will be checked.

In visits V1, V2 participants must present themselves in fasting conditions of 8 hours to obtain blood. In addition, in visits V2 and V3, participants will be asked for the presence of adverse events that could be associated with the consumption or withdrawal of the study products.

The products will be given in the V1 visit so that the participants will have all the necessary treatment to carry out the 8 weeks of study with the corresponding product.

During the study and starting from visit V0 once the volunteer has been included in the study and signed the informed consent, participants will record AR symptomatology and/or the use of AR medication on a daily basis by using the CSMS questionnaire described by Pfaar O. et al. in an online format using the Microsoft Forms application. During the study, the research team will monitor compliance of the online questionnaire by the volunteer.

Volunteers will be encouraged to maintain their dietary habits and to maintain their regular practice of physical activity during the study.

Descriptive variables related to AR and demographic variables will be obtained from participants of the study by clinical history and interviewing at visit V0.

In visits V1, V2 and V3 of the study, health-related quality of life data will be obtained by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) according to Juniper, E, et al.

For the collection of faeces in visits V1, V2 and V3, participants will be previously provided with a faeces collection kit (two different labelled tubes, one for metagenomic analysis and other for IgA determination will be provided).

Eligibility criteria: Inclusion Criteria:

1. Men and women between 18 and 60 years of age.
2. Present a medical history of ARs defined according to the International Consensus on Rhinitis for at least 2 years.
3. Present a positive IgE sensitization test to dust mite allergen during the last 5 years.

   \* Participants may present various sensitizations to different allergen in addition to allergy to dust mite.
4. Present the criteria for moderate-to-severe persistent AR phenotype according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification:

   * The intensity of signs and symptoms interferes with sleep; interferes with daily activities, sports and leisure; interferes with work activities; and symptoms present are troublesome.
   * The symptoms are present more than 4 days a week and during more than 4 consecutive weeks.
5. Present symptomatology at the pre-selection visit. This is, present, according to ARIA criteria, 2 or more of the following symptoms during more than 1 hour a day: water rhinorrhoea; sneezing, especially paroxysmal; nasal obstruction; nasal puritis; with or without conjunctivitis.
6. Sign the informed consent form.

Exclusion Criteria:

1. Age under 18 or over 60 years old.
2. Present intolerances and/or food allergies related to the products of the study.
3. Being pregnant or intending to become pregnant.
4. Be in breastfeeding period.
5. Participate in or have participated in a clinical trial or nutritional intervention study in the last 30 days prior to inclusion in the study.
6. Present some chronic gastrointestinal disease.
7. Clinical history of anemia.
8. Having received antibiotic treatment up to 30 days before the start of the study.
9. Having received immunotherapy treatment for dust mite allergen before the start of the study and during the study.
10. Having received immunotherapy treatment for allergens other than dust mites up to 30 days before the start of the study and during the study.
11. Taking probiotics, prebiotics and/or postbiotics up to 30 days before the start of the study and during the study.
12. Present any disease with immune system involvement (HIV, autoimmune disease, hepatitis, cancer, etc.).
13. Having received chemotherapy or other immunosuppressive therapy during the previous year.
14. Medical history of surgical procedures of nasal cavity and sinuses, recent surgery of gastrointestinal tract or bariatric surgery (ever).
15. Being unable to follow the study guidelines.

Primary outcomes:
measure: Combined Symptoms and Medication Score
timeFrame: Daily for the thirteen weeks of the study.
Secondary outcomes:
measure: Nasal and conjunctival symptoms (dSS)
timeFrame: Daily for the thirteen weeks of the study.
measure: Nasal symptoms.
timeFrame: Daily for the thirteen weeks of the study.
measure: Conjunctival symptoms
timeFrame: Daily for the thirteen weeks of the study.
measure: Use of rescue medication.
timeFrame: Daily for the thirteen weeks of the study.
measure: Number of days without medication.
timeFrame: Daily for the thirteen weeks of the study.
measure: Use of other medications for AR.
timeFrame: Daily for the thirteen weeks of the study.
measure: Change in experienced troublesome functional impairments.
timeFrame: At week 2, week 10 and week 14.
measure: Change in serum IL-10 levels.
timeFrame: At week 2 and week 10.
measure: Change in serum TGF-β levels.
timeFrame: At week 2 and week 10.
measure: Change in serum IL-12 levels.
timeFrame: At week 2 and week 10.
measure: Change in serum IFN-γ levels.
timeFrame: At week 2 and week 10.
measure: Change in serum IgE levels.
timeFrame: At week 2 and week 10.
measure: Change in serum IL-4 levels.
timeFrame: At week 2 and week 10.
measure: Change in serum IL-13 levels.
timeFrame: At week 2 and week 10.
measure: Change in serum IL-8 levels.
timeFrame: At week 2 and week 10.
measure: Change in serum IL-19 levels.
timeFrame: At week 2 and week 10.
measure: Change in stool IgA levels.
timeFrame: At week 2, week 10 and week 14.
measure: Metagenomic analysis.
timeFrame: At week 2, week 10 and week 14.
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Eurecat
Study officials:
affiliation: UTNS (Eurecat-Reus)
name: Josep M Del Bas, PhD
role: PRINCIPAL_INVESTIGATOR
References: