Efficacy, Safety and Underlying Mechanisms of Sphenopalatine Ganglion Acupuncture for Seasonal Allergic Rhinitis

Study Overview
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Brief Summary
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In recent years, a number of randomized controlled trials have confirmed the efficacy and safety of acupuncture in the treatment of allergic rhinitis (AR). Indeed, the latest American clinical guidelines recommended acupuncture treatment for AR patients who are interested in non-pharmacological treatment. In conventional acupuncture treatment for AR, needles are inserted at specific acupoints in the body; with several studies demonstrating acupuncture of sphenopalatine ganglion (SPG) to improve nasal symptoms and quality of life in nasal inflammatory diseases. The investigators hypothesize that, compared with sham acupuncture and rescue medication (RM), active SPG acupuncture combined with RM would lead to greater improvements in symptoms score and reduction in overall need for antihistamines. To test this hypothesis the investigators design a randomized, double blind, controlled trial to evaluate the efficacy of SPG acupuncture in pollen-induced seasonal AR patients and to explore the potential underlying mechanisms.

Official Title
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Efficacy, Safety and Underlying Mechanisms of Sphenopalatine Ganglion Acupuncture for Seasonal Allergic Rhinitis: a Randomized, Double-blind, Placebo Controlled Study

Conditions
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Seasonal Allergic Rhinitis

Intervention / Treatment
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* Procedure: SPA acupuncture
* Procedure: sham acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: history of physician-diagnosed SAR with at least 2 years of typical symptoms, and TNSS>=6 at v0. positive skin prick test (SPT) and/or positive serum antigen specific IgE to local seasonal pollens (Giant Ragweed, Mugwort, Goosefoot, etc) Exclusion Criteria: oral steroids within 4 weeks prior to recruitment nasal steroids and/or antihistamine 2 weeks prior to recruitment perennial AR any respiratory infection within the previous 4 weeks prior to recruitment history of nasal polyps, asthma or autoimmune disorders previously received acupuncture therapy for AR within 1 month prior to recruitment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SPA acupuncture<br>active SPG acupuncture plus rescue medication (AA group) | Procedure: SPA acupuncture<br>* For patients in the AA group, acupuncture was performed at a selected point in the SPG by inserting the needle from the lower border of the zygomatic arch, posterior to the suture protuberance between the zygomatic process and temporal process. The needle was directed obliquely anteriorly, until nearly the whole needle was beneath the skin, and then rotated until the patient felt de-qi sensations . The patients in the AA group received four courses of active acupuncture(visit 1,2,3 and 4) within first two weeks, and then followed-up for a further 2 weeks (visit 5 and visit 6 ).<br>|
| Sham Comparator: sham acupuncture<br>sham-SPG acupuncture plus rescue medication (SA group) | Procedure: sham acupuncture<br>* For patients in the SA group, the needle was inserted at the same acupuncture point as for patients in the AA group, but to a depth of only 2-3cm and the procedure of rotating, twirling and thrusting the needle was repeated. During the acupuncture process, the acupuncturist sat on the side of the participant, where the patient could neither see the acupuncturist's face nor the length of the needle. The patients in the SA group received four courses of active acupuncture(visit 1,2,3 and 4) with first two weeks, and then followed-up for a further 2 weeks (visit 5 and visit 6).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline symptom scores at visit 4 | Patients recorded nasal and ocular symptom severity during the trial. Four nasal symptoms (itching, sneezing, rhinorrhoea and nasal obstruction) and two ocular symptoms (ocular itch and watery eyes) were individually graded on a ten-point scale (0, no symptoms; 1-3, mild symptoms; 4-7, moderate symptoms; 8-10, severe symptoms). Our primary outcome is TNSS change from baseline at the end of four-acupuncture treatment at Visit 4 (15 minutes after the fourth acupuncture ). The investigator will compare the symptom scores between the active acupuncture group and the sham acupuncture group. | Symptom scores will be assessed at baseline (V0), visit 4( V4). V4 is within 15 minutes after the fourth acupuncture. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rescue medication score | when the symptoms were very severe and could not tolerated, the patients could use loratadine as rescue medication. The need for rescue medication was assessed as rescue medication score (RMS), analyzed as the weekly sum of daily use of Loratadine (10mg/d, equivalent to 1 point) or nasal corticosteroid spray (2 points) | RMS will be assessed at baseline (V0), and each visit. V1 to V4 is within two weeks. V5 is one week after the fourth acupuncture, and V6 is two weeks after the fourth acupuncture. There is no acupuncture during both V5 and V6 | 
| SNOT-22 | SNOT-22 is assessed to evaluate the quality of life of the SAR patients. | SNOT-22 will be assessed at baseline (V0), and each visit. V1 to V4 is within two weeks. V5 is one week after the fourth acupuncture, and V6 is two weeks later. There is no acupuncture during both V5 and V6. | 
| nasal patency | Eccovision acoustic rhinometry (Hood Labs, Pembroke, USA) was used to measure the total nasal cavity volume (NCV) and minimum cross-sectional area (MCA). The ATMO 300 Rhinomanometer (ATMOS MedizinTechnikGmbH&Co., Feldkirch, Germany) was used to measure the nasal airway resistance (NAR) by anterior active rhinomanometry. | NCV, NAR and MCA will be assessed at baseline (V0), and each visit. V1 to V4 is within two weeks. V5 is one week after the fourth acupuncture, and V6 is two weeks after the fourth acupuncture. | 
| neuropeptides in nasal secretions | The levels of neuropeptides; including substance P, vasoactive intestinal peptide (VIP) , neuropeptide Y (NPY)) will be analysed using ELISA. | Nasal secretions can be obtained at each visit. V1 to V4 is within two weeks. V5 is one week later and V6 is two weeks later. There is no acupuncture during both V5 and V6. | 
| inflammatory cytokines in nasal secretions | The levels of inflammatory cytokines; including interferon-γ (IFN-γ), tumor necrosis factor-α(TNF-α), interleukin (IL)-5, IL-8, IL-17A, and eotaxin in the supernatants will be analyzed using the Luminex System. | Nasal secretions can be obtained at each visit. V1 to V4 is within two weeks. V5 is one week later and V6 is two weeks later. There is no acupuncture during both V5 and V6. | 
| adverse events | Any adverse event following acupuncture was assessed by physicians and patients. Patients were instructed to record any unexpected signs, symptoms, and feelings during the entire trial period. the pain score will be recorded during V1-V4. | adverse events will be recorded at V1 to V4. V1, V2, V3, and V4 is within two weeks. V5 is one week after fourth treatment and V6 is two weeks later. There is no acupuncture during both V5 and V6. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acupuncture, sphenopalatine ganglion, seasonal allergic rhinitis, neuropeptides, inflammatory cytokines, neuro-immune interactions