An interventional study of Intratonsillar immunotherapy (ITIT) and Subcutaneous immunotherapy (SCIT) in Allergic Rhinitis, sponsored by Xu Yu. Recruiting at 1 site in China. Open to participants aged 5 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-07-26.
Sponsored by Xu Yu · Not applicable, Interventional, and Treatment
This is a prospective, open-label, positive parallel controlled, blinded endpoint clinical study designed to compare the safety and efficacy of "Intratonsillar Immunotherapy of Standardized Dust Mite Allergen Extracts (Novo Helisen-Depot, Allergopharma, Merck, Germany)" with Subcutaneous Immunotherapy in patients with "Dust Mite Allergic Rhinitis."
Participants will be evaluated for safety and efficacy throughout the entire three-year period.
Background:
Allergic Rhinitis (AR) presents both nasal and non-nasal symptoms. The global incidence of AR is rising, causing a significant burden. Seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) are the two related clinical divisions of AR. Allergen immunotherapy (AIT) is a treatment involving the injection of specific allergens into the body. Studies have evaluated the effectiveness and safety of subcutaneous (SCIT), sublingual (SLIT), and intra-lymphatic immunotherapy (ILIT). The mechanisms underlying AIT involve both innate and acquired immunity. AIT modulates the activity of various immune cells, including dendritic cells, innate lymphoid cells (ILCs), and regulatory T cells (Tregs).
Intra-lymphatic inoculation (ILIT) has been studied in animals for its ability to improve T cell response to antigens. Studies have found that direct injection of antigens into lymph nodes can lead to improved T cell response and more efficient delivery of the antigen to subcutaneous lymph nodes. ILIT has been effective in treating atopic dermatitis, producing targeted IgG antibodies, enhancing lymphocyte responses, and treating viral and tumor challenges. It has also been effective in treating allergies and reducing symptoms of allergic rhinitis in mice. Studies have found ILIT to be effective in treating atopic dermatitis in dogs caused by common allergens and insect bite hypersensitivity in horses caused by biting midges. In general, animal studies support the use of ILIT as a safe and effective means to induce IgG and T cell responses with fewer treatments and lower doses compared to subcutaneous injection across a range of species.
Objectives:
The primary objective is to explore the efficacy, clinical value, and possible mechanism of action of Intratonsillar Immunotherapy (ITIT) by recording and analyzing the questionnaire scores after ITIT versus SCIT, while comparing the trend of bio-indicator changes in these two treatments.
Primary Endpoint:
Combined Symptom and Medication Score (CSMS): CSMS serves as the primary efficacy endpoint, tracking changes in participant symptoms and assessing the sustainability and stability of treatment effects. It comprises:
Allergen-induced symptom score: Scored from 0 (no symptoms) to 3 (most severe symptoms) for nasal congestion, rhinorrhea, nasal itching, sneezing, eye itching, and tearing, with the average yielding the symptom score (SS).
Emergency medication use related to allergy symptoms: Assigned points based on antihistamine (1 point/day), nasal corticosteroid (2 points/day), and oral corticosteroid (3 points/day) usage, with the highest value determining the medication score (MS).
CSMS (0-6) = SS (0-3) + MS (0-3). Recorded at baseline and 1, 2, 3, 6, 12, 24, and 36 months post-dust mite extract treatment.
Adverse Reactions: Participants were observed for 30 minutes post-injection and encouraged to report any adverse events during follow-up. Adverse reactions were classified as local (LR) or systemic (SR) according to the World Allergy Organization Subcutaneous Immunotherapy Response Classification System. Detailed records included occurrence time, number of injections, clinical manifestations, and management measures.
Study Population:
A total of 120 screened participants will be required to enroll 60 subjects in each group, with an age range of 5-65 years.
Sites/Facilities Enrolling Participants:
Renmin Hospital of Wuhan University will recruit participants.
Description of Study Intervention:
In this study, participants who meet the enrollment criteria will be randomly assigned to two groups. The random assignment will be performed by an independent investigator using a computer-generated sequence of random numbers. The assignment process will be conducted before participants are enrolled to ensure fairness and randomness in the grouping. Each group will be assigned an equal number of participants to ensure the objectivity and comparability of the studies.
Due to the obvious differences between the treatment methods of the experimental group and the control group, it is difficult to blind the subjects, researchers, and evaluators. Therefore, a non-blind experimental design is adopted. To minimize bias, blind data review will be employed.
1,042 studies on the registry are indexed under Rhinitis, Allergic; 91 are open to participants now.
This study's planned enrollment of 120 is above the median of 90 across 858 interventional studies indexed under Rhinitis, Allergic.
Browse Rhinitis, Allergic studies →Xu Yu is the lead sponsor of 2 studies on the registry; 2 are open to participants now.
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Diagnosis in accordance with ARIA guidelines, based on:
① Symptoms: Two or more symptoms such as paroxysmal sneezing, watery nose, nasal itching, and nasal congestion, with symptoms lasting or accumulating for more than 1 hour per day. May be accompanied by eye symptoms such as tearing, eye itching, and eye redness.
② Signs: Common nasal mucosa pale, edema, nasal watery secretions.
Have a history of allergic rhinitis caused by atopic allergens and one of the following:
① No significant relief after drug treatment.
② Do not want to continue taking medication for a long time.
③ Long-term drug treatment can produce adverse side effects.
Exclusion Criteria:
A history of chronic sinusitis, including at least two of the following symptoms (at least one of which should be nasal congestion or runny nose):
① Nasal congestion, runny nose, facial pressure, or pain.
② Having a diminished or lost sense of smell.
③ Endoscopic or CT examination showed signs of sinusitis.
The intervention of ITIT will be a series of 3 injections of a commercially-available standardized dust mite allergen extracts (Novo Helisen-Depot, Allergopharma, Merck, Germany) given every four weeks into tonsil through guidance using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. The specific doses are 5 TU (0.1 ml, the first injection), 50 TU (0.1 ml, the second injection), and 50 TU (0.1 ml, the third injection). Before each injection, patients will take one tablet of antihistamine.
Procedure: Intratonsillar immunotherapy (ITIT)
The same drugs will be used in active comparator. SCIT consists of two stages: the accumulation stage and the maintenance stage. During the initial 14 weeks, patients will receive sequential subcutaneous injections as follows: (1) 1st vial: 0.1 mL, 0.2 mL, 0.4 mL, and 0.8 mL; (2) 2nd vial: 0.1 mL, 0.2 mL, 0.4 mL, and 0.8 mL; (3) 3rd vial: 0.1 mL, 0.2 mL, 0.4 mL, 0.6 mL, 0.8 mL, and 1.0 mL of allergen, achieving a maintenance dose of 5000 TU. Subsequently, maintenance therapy involves subcutaneous injections of 5000 TU (1.0 mL, 3rd vial) every 4-6 weeks. The intervention process before and after each injection is similar to that of the ITIT group.
Procedure: Subcutaneous immunotherapy (SCIT)
During injection, the operator needs to gently shake the injection bottle about 20 times, the drug must be mixed to ensure the consistency of allergen concentration, and carefully check the patient's name and concentration on the bottle. Allergy extracts should not be injected intravenously, so the syringe will be aspirated to avoid inadvertent intravascular injection. Before each injection, after inserting the needle into the selected tonsil, before injecting the dose, the investigator will slightly pull the plunger of the syringe. If blood returns from the syringe, the syringe, and its contents will be discarded. The other tonsil will be selected and a new syringe will be prepared.
Injection requires shaking bottle 20x to mix drug for consistency. Verify patient name \& concentration. Use 1 ml skin test syringe for deep subcutaneous injection at 45° angle, 1 cm into outer upper arm. Lift skin folds for deeper injection, avoid subcutaneous, muscular or intravascular. Inject slowly, 1 min for 1 ml. Avoid shallow injections which may cause local side effects. Alternate between left \& right arm for 5 min after injection for compression.
Combined Symptom and Medication Score (CSMS)
Combined Symptom and Medication Score (CSMS) serves as the primary efficacy endpoint, tracking changes in participant symptoms and assessing the sustainability and stability of treatment effects. It comprises: Allergen-induced symptom score: Scored from 0 (no symptoms) to 3 (most severe symptoms) for nasal congestion, rhinorrhea, nasal itching, sneezing, eye itching, and tearing, with the average yielding the symptom score (SS). Emergency medication use related to allergy symptoms: Assigned points based on antihistamine (1 point/day), nasal corticosteroid (2 points/day), and oral corticosteroid (3 points/day) usage, with the highest value determining the medication score (MS). CSMS (0-6) = SS (0-3) + MS (0-3). Recorded at baseline and 1, 2, 3, 6, 12, 24, and 36 months post-dust mite extract treatment.
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
Number of Participants with Local or Systemic Adverse Reactions
Participants will be observed for 30 minutes post-injection and encouraged to report any adverse events during follow-up. Adverse reactions are classified as local reaction (LR) or systemic reaction (SR) according to the World Allergy Organization Subcutaneous Immunotherapy Response Classification System. Detailed records include occurrence time, number of injections, clinical manifestations, and management measures.
Time frame: After each treatment. Up to 36 months
Visual Analog Scale (VAS)
Pain perception of allergy symptoms during treatment will be evaluated using a scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates maximum pain.
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
Absolute Value and Percentage of Blood Leukocytes
Changes in blood eosinophil absolute value (EOS), eosinophil percentage (EOS%), basophil absolute value (BAS), and basophil percentage (BAS%) will be evaluated.
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
Concentration of Key Serum Cytokines
Changes in key serum cytokines, including TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, and IL-17, will be evaluated at the same intervals as CSMS.
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
Concentration of Serum Immune Globulins
Changes in serum total IgE (tIgE), IgA, IgG, and specific IgE (sIgE) will be evaluated at the same intervals as CSMS.
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
Proportion of Blood T Cell Differentiation
Changes in the proportion of blood T cell differentiation (Th, Tfh, Tfr, Treg, Tfc, Tex, etc.) will be evaluated.
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
RQLQ
Administration of questionnaires, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ).
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
Concentration of FeNO
Change of FeNO
Time frame: Pre-intervention screening period; 3 months, 6 months, 12 months, 24 months, 36 months after the first intervention. Up to 36 months
Plan to share: Yes — Two years after the completion of the trial, data will be published on the EDC of Metz Medical (https://edc-cloud.medsci.cn/).
Supporting information: Study protocol, Clinical study report
Time frame: Two years after the completion of the trial
Access criteria: Upon approval of the request, access to the de-identified individual patient-level data will be provided. Before accessing the requested information, a data sharing agreement (a non-negotiable contract for data visitors) must be signed.
Data sharing details ↗ · edc-cloud.medsci.cn
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