Efficacy, Safety and Underlying Mechanisms of Sphenopalatine Ganglion Acupuncture for Perennial 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 perennial AR patients (allergic to indoor allergens, including house dust mite, fungi, animal dander and so one) and to explore the potential underlying mechanisms.

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

Conditions
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Perennial 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: 1. history of physician-diagnosed PAR with at least 2 years of typical symptoms 2. course on each onset lasting at least 4 weeks 3. skin prick test and/or serum antigen specific IgE positive to indoor allergens(sIgE≥0.7kU/L,≥class 2) 4. good patient compliance on acupuncture treatment 5. total nasal symptom scores(TNSS)>6 at V0 Exclusion Criteria: 1. oral steroids within 4 weeks prior to recruitment 2. nasal steroids and/or antihistamine 2 weeks prior to recruitment 3. seasonal AR 4. any respiratory infection within the previous 4 weeks prior to recruitment 5. history of nasal polyps, nasal septum deviation, asthma or autoimmune disorders 6. previously received acupuncture therapy for AR within 1 month prior to recruitment 7. women during pregnancy or lactation

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), twice a week during weeks 1 and 2, and then followed-up for a further 2 weeks (visit 5 during week 3 and visit 6 during week 4).<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), twice a week during weeks 1 and 2, and then followed-up for a further 2 weeks (visit 5 during week 3 and visit 6 during week 4).<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 total nasal symptom scores 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 at the second week 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 be 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, V2, V3, and V4 is on Day 1, Day 4, Day 8 and Day 11, respectively(+/- 1 day). V5 is at the third week and V6 is at the fourth week. There is no acupuncture during both V5 and V6. | 
| rhinoconjunctivitis quality of life questionnaire (RQLQ) | RQLQ is assessed to evaluate the quality of life influenced by PAR. It offers 28 items related quality of life and each item ranges from 0 to 6, with lower scores implying a better health-related quality of life. | RQLQ will be assessed at baseline (V0), and each visit. V1, V2, V3, and V4 is on Day 1, Day 4, Day 8 and Day 11, respectively(+/- 1 day). V5 is at the third week and V6 is at the fourth week. 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, V2, V3, and V4 is on Day 1, Day 4, Day 8 and Day 11, respectively(+/- 1 day). V5 is at the third week, and V6 at the fourth week. | 
| neuropeptides in nasal secretions | The levels of neuropeptides; including substance P, vasoactive intestinal peptide (VIP) , neuropeptide Y (NPY)) will be analysed using ELISA. The unit of all these parameters is ng/ml. | Nasal secretions can be obtained at baseline (V0), V4,V5 and V6. V4 is at the second week. V5 is at the third week and V6 is at the fourth week. 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. The unit of all these parameters is pg/ml. | Nasal secretions can be obtained at baseline (V0), V4 ,V5 and V6. V4 is at the second week. V5 is at the third week and V6 is at the fourth week. 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. | adverse events will be recorded at baseline (V0), and each visit. V1, V2, V3, and V4 is on Day 1, Day 4, Day 8 and Day 11, respectively(+/- 1 day). V5 is at the third week and V6 is at the fourth week. 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, perennial allergic rhinitis, neuropeptides, inflammatory cytokines, neuro-immune interactions