Washed Microbiota Transplantation for Allergic Rhinitis

Official title

Efficacy and Safety of Washed Microbiota Transplantation for Allergic Rhinitis: A Randomized, Double-blind, Placebo-controlled Study

Overview

Allergic rhinitis (AR) is characterized by sneezing, nasal congestion, nasal itching and nasal leakage and is caused by immunoglobulin E (IgE)-mediated reactions to inhaled allergens. Increasing evidence showed that gut microbiota could influence the development of AR, and we found that washed microbiota transplantation (WMT) could improve nasal symptoms in clinical practice. This clinical trial aims to evaluate the efficacy and safety of WMT for AR.

Detailed description

Allergic rhinitis (AR) is characterized by sneezing, nasal congestion, nasal itching and nasal leakage and is caused by immunoglobulin E (IgE)-mediated reactions to inhaled allergens. The prevalence of AR has been reported from 5% to 50% worldwide which is dependent on the method of diagnosis and age of participants studied. AR is often co-morbid with asthma and/or conjunctivitis, which affects patients' daily life and carries a huge economic burden.

Increasing evidence showed that gut microbiota can influence the development of AR. Fecal Microbiota transplantation (FMT), the most classic way to treat diseases using gut microbiota, refers to the transplantation of functional microbiota in the feces of healthy people into the intestines of patients. It can reconstruct the overall gut microbiota of patients, thus treating gastrointestinal disease and external gastrointestinal diseases of patients. Washed microbiota transplantation (WMT), a new stage of FMT, is based on the automatic microfiltration machine (GenFMTer, Nanjing, China) and the following repeated centrifugation plus suspension with support from specific facilities. Compared with manual FMT, WMT can reduce the rate of adverseevents (such as fever, diarrhea, abdominal pain, abdominal distension, nausea and vomiting, etc.) without affecting the efficacy.

In clinical practice, we found that WMT could significantly improve the nasal symptoms of AR. This clinical trial aims to evaluate the efficacy and safety of WMT for AR.

Interventions

• Drug Washed Microbiota Transplantation
  Patients take four capsules containing washed microbiota once a day for five consecutive days
• Drug Placebo
  Patients take four capsules in the same packaging as the experimental group once a day for five consecutive days

Primary outcome measures

• Changes in the reflective total nasal symptom score (rTNSS) [Time frame: baseline, one weeks, four weeks, twelve weeks post WMT]

Secondary outcome measures (8)

• Changes in the rhinoconjunctivitis quality of life questionnaire (RQLQ) score [Time frame: baseline, one weeks, four weeks, twelve weeks post WMT]
• Changes in the single reflective nasal symptoms score [Time frame: baseline, one weeks, four weeks, twelve weeks post WMT]
• Changes in the concentration of specific IgE [Time frame: baseline, one day, four weeks, twelve weeks post WMT]
• Changes in the concentration of inflammatory factors [Time frame: baseline, one day, four weeks, twelve weeks post WMT]
• Changes in the number of immune cell [Time frame: baseline, one day, four weeks, twelve weeks post WMT]
• The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0 [Time frame: One day, one week, four weeks, twelve weeks post WMT]
• Changes in the Modified Lund-Kennedy endoscopic score [Time frame: baseline, four weeks, twelve weeks post WMT]
• Changes in composition and metabolites of gut microbiota and nasal microbiota [Time frame: baseline, one day, four weeks, twelve weeks post WMT]

Eligibility criteria

Inclusion criteria

• Age 18-65 years old.
• Meets the diagnostic criteria for allergic rhinitis.
• rTNSS score greater than or equal to 6 points.
• The subject or his/her legal representative gives informed consent, fully understands the purpose of the study, is able to communicate effectively with the investigator, and comprehends and complies with the requirements set forth in the study.

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Exclusion criteria

• Patients with acute nasosinusitis or upper respiratory tract infection.
• Patients diagnosed with chronic sinusitis, nasal septum deviation, nasal polyps, nasal tumors, and other nasal diseases or have undergone nasal surgery.
• Antibiotics, PPI, probiotics, and other drugs that alter gut microbiota were used in the past two weeks.
• Patients with poor lung function.
• Patients with severe liver, kidney, and heart diseases
• Patients with known psychiatric or neurological diseases.
• Patients who use antihistamines, glucocorticoids, decongestants, mast cell membrane stabilizers, leukotriene antagonists in the past two weeks.
• According to the judgment of the investigator, the subjects are not suitable to participate in this clinical study, or participation in this clinical study cannot guarantee the rights and interests of the subjects.

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Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical U — Nanjing

Publications

• Wise SK, Damask C, Roland LT, Ebert C, Levy JM, Lin S, Luong A, Rodriguez K, Sedaghat AR, Toskala E, Villwock J, Abdullah B, Akdis C, Alt JA, Ansotegui IJ, Azar A, Baroody F, Benninger MS, Bernstein J, Brook C, Campbell R, Casale T, Chaaban MR, Chew FT, Chambliss J, Cianferoni A, Custovic A, Davis EM, DelGaudio JM, Ellis AK, Flanagan C, Fokkens WJ, Franzese C, Greenhawt M, Gill A, Halderman A, Hoh PMID 36878860
• Bousquet J, Anto JM, Bachert C, Baiardini I, Bosnic-Anticevich S, Walter Canonica G, Melen E, Palomares O, Scadding GK, Togias A, Toppila-Salmi S. Allergic rhinitis. Nat Rev Dis Primers. 2020 Dec 3;6(1):95. doi: 10.1038/s41572-020-00227-0. PMID 33273461
• Martensson A, Cervin-Hoberg C, Huygens F, Lindstedt M, Sakellariou C, Greiff L, Cervin A. Upper airway microbiome transplantation for patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2023 Jun;13(6):979-988. doi: 10.1002/alr.23122. Epub 2023 Jan 1. PMID 36515012
• Zhang T, Lu G, Zhao Z, Liu Y, Shen Q, Li P, Chen Y, Yin H, Wang H, Marcella C, Cui B, Cheng L, Ji G, Zhang F. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein Cell. 2020 Apr;11(4):251-266. doi: 10.1007/s13238-019-00684-8. Epub 2020 Jan 9. PMID 31919742
• Schaefer M, Zimmermann K, Enck P. Probiotic treatment (Enterococcus faecalis) improves symptoms of seasonal allergic rhinitis: A randomized controlled trial. Int Forum Allergy Rhinol. 2023 Oct;13(10):1974-1977. doi: 10.1002/alr.23154. Epub 2023 Apr 7. No abstract available. PMID 36922364
• Anania C, Di Marino VP, Olivero F, De Canditiis D, Brindisi G, Iannilli F, De Castro G, Zicari AM, Duse M. Treatment with a Probiotic Mixture Containing Bifidobacterium animalis Subsp. Lactis BB12 and Enterococcus faecium L3 for the Prevention of Allergic Rhinitis Symptoms in Children: A Randomized Controlled Trial. Nutrients. 2021 Apr 16;13(4):1315. doi: 10.3390/nu13041315. PMID 33923532
• Kang MG, Han SW, Kang HR, Hong SJ, Kim DH, Choi JH. Probiotic NVP-1703 Alleviates Allergic Rhinitis by Inducing IL-10 Expression: A Four-week Clinical Trial. Nutrients. 2020 May 15;12(5):1427. doi: 10.3390/nu12051427. PMID 32429063

Identifiers

NCT: NCT06372184 · WMT-AR-RCT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗