Effect and Underlying Immunological Mechanisms of Sublingual Immunotherapy in Allergic Rhinitis

Effect and Underlying Immunological Mechanisms of Sublingual Immunotherapy in Seasonal Allergic Rhinitis: a Randomized, Double Blind, Placebo Controlled Trial

Allergic rhinitis (AR) is a common Ig-E mediated disease of nasal mucosa, induced by an immunoglobulin E (IgE)-mediated reaction in the allergen-sensitized subjects, affecting 10% to 40% of the world population. AR could be divided into two kinds, perennial AR and seasonal AR (SAR). Allergen specific immunotherapy (AIT) is the only etiological treatment available for AR. Traditionally, AIT is divided into 2 types, subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), both of which are effective and safe alternatives.

The trial is a randomized, double-blind, placebo-controlled trial. 72 eligible SAR patients, who were sensitized to sweet sagewort (artemisia annua), were enrolled into the trial, followed by either a 32-week SLIT schedule, where the maintenance dose would be reached within 5 weeks, or placebo SLIT schedule. Standardized depot preparations of sweet sagewort (artemisia annua) extract (Zhejiang Wolwo Bio-pharmaceutical Co., Ltd., China ) were administered by means of sublingual drops.

Study Overview

• Status: Completed
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Drug: sublingual immunotherapy drops; Drug: Placebo drops

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Beijing Tongren Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female outpatients aged 18 to 60 years (inclusive).
• With history of SAR for at least two years, with/without conjunctivitis and asthma
• Two or more nasal symptoms scores were ≥ 2 points during July - October in the last year.
• Sensitised to artemisia annua (specific IgE level ≥ 3.5 kilounit per liter).
• Patients who have been informed of the nature and aims of the study and have given their written consent, willing to comply with the protocol.
• Patients who are able to understand the information given and the consent and complete the daily record card.

Exclusion Criteria:

• Patients whose Humulus- or Artemisiifolia-specific immunoglobulin E (IgE) levels (ImmunoCAP) same as or higher than Artemisia-specific immunoglobulin E (IgE) level.
• Patients with oral diseases/ allergies within the run-in period.
• Patients accepted any kind of operations within 4 weeks of the run-in period.
• Patients applied for systemic glucocorticoids within 4 weeks in the run-in period.
• Patients with perennial AR.
• Patients with any nasal condition that could confound the results of the study (chronic rhinitis, chronic rhinosinusitis with/without polyps).
• Whatever the co-sensitization leading to clinically relevant AR, conjunctivitis or asthma likely to significantly change the symptoms of the patient throughout the study.
• Patients with comorbidity of severe asthma.

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
Active Comparator: artemisia annua (sweet sagewort) allergen extract drops; Drug: sublingual immunotherapy drops	Drug: sublingual immunotherapy drops; artemisia annua (sweet sagewort) allergen extract drops
Placebo Comparator: Placebo drops; Drug: sublingual placebo drops	Drug: Placebo drops; sublingual placebo drops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline symptom scores at Week 16	Primary outcome is the assessment data from all patients whom will record on diary cards their symptom scores based on visual analog scales, ranging from 0(asymptomatic) to 3(most severe).	at baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Assessment data from all patients whom will record on diary cards their quality-of-life measures for rhinitis(rhinoconjunctivitis quality of life questionnaire,RQLQ), including 28 questions, ranging from 0 (do not affect quality of life) to 6 (severely affect quality of life).	at the pollen season of 2016, baseline, Week 16, Week 32, 6 months after discontinuation of treatment
Medication scores	Assessment data from all patients whom will record on diary cards their medication usage.	at the pollen season of 2016, baseline, Week 16, Week 32, 6 months after discontinuation of treatment
Immunologic Changes-IgE	Changes in total serum IgE, specific IgE levels in peripheral blood.	at baseline, Week 16, Week 32
Immunologic Changes-M2 population	Changes in M2 population in peripheral blood and nasal secretion (Flow cytometry).	at baseline, Week 16, Week 32
Change of symptom scores	Assessment data from all patients whom will record on diary cards their symptom scores based on visual analog scales.	at the pollen season of 2016, Week 16 and 6 months after discontinuation of treatment

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital
• Collaborators: Zhejiang Wolwo Bio-Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): October 30, 2018
• Study Completion (Actual): October 30, 2018

Study Registration Dates

• First Submitted: August 2, 2018
• First Submitted That Met QC Criteria: August 26, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal
• Other Study ID Numbers: TR-SLIT-IMMUNO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No