Acupuncture at the Sphenopalatine Ganglion in the Treatment of Moderate-to-severe Seasonal Allergic Rhinitis

Study Overview
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Brief Summary
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Allergic rhinitis (AR) is an immunoglobulin E-mediated inflammatory disease1 caused by hypersensitivity of the immune system to an allergen, affecting 100 million people in Europe 2and 400 million of the global population.The etiology of AR is multifactorial, resulting primarily from genetic predisposition, immunological response, and environmental pollutants.AR traditionally has been classified as seasonal (SAR) or perennial (PAR) depending on the causes and duration of symptoms. Some patients with AR prefer complementary and alternative medicine for their symptoms, with nearly 20% receiving acupuncture. According to the updated practice parameter of rhinitis in 2020, the use of acupuncture for the treatment of AR was not recommended due to a lack of well-controlled studies. The sphenopalatine ganglion (SPG), located under a thin (1-2 mm) layer of mucosa in the pterygopalatine fossa, consists of sensory fibers that innervate the nasopharynx, nasal cavity, and palate.Several studies have reported the benefit of SPG stimulation in chronic cluster headache and acute ischaemic stroke. Compared with traditional acupoints selected on basis of traditional meridian theory, acupuncture at SPG(inserting a needle through SPG acupoint (near ST7, Xiaguan) to reach and directly stimulate the SPG) may help patients ameliorate nasal symptoms immediately and improve quality of life by increasing sympathetic nerve excitability, but the evidence is inconclusive. We have designed this three-armed, randomized trial to investigate the efficacy and safety of acupuncture at SPG for the treatment of SAR. We hypothesize that acupuncture at SPG plus rescue medication is superior to sham acupuncture plus RM and RM alone in the treatment of SAR.

Official Title
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Effect of Acupuncture at the Sphenopalatine Ganglion in the Treatment of Moderate-to-severe Seasonal Allergic Rhinitis

Conditions
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Seasonal Allergic Rhinitis

Intervention / Treatment
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* Other: Acupuncture group
* Other: Placebo acupuncture group
* Other: Rescue medication group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and ≤ 75 years; History of moderate to severe SAR symptoms (Visual analog scale(VAS) >50 mm, range, 0 cm[not at all bothersome] to 100 mm[extremely bothersome]) for more than 4 days/weeks, and more than 4 consecutive weeks with at least two years' duration; Positive skin prick test to grass and birch pollen or/and serum-specific IgE test; Ability to complete the medical information form and sign a written informed consent. Exclusion Criteria: History or current evidence of perennial allergic rhinitis, acute sinusitis, allergic asthma, pneumonia; autoimmune disorders, or severe chronic inflammatory diseases; History of nasal rhinopolypus or abnormalities; Intake of antihistamines, anticholinergics, corticosteroids, decongestants, or antibiotics during the 1 month prior to beginning the study; History of systemically administered corticosteroids within 6 months or specific immunotherapy, allergy desensitization therapy within 1 year before enrollment; Serious uncontrolled blood coagulation disorder, cardiovascular disorder, severe hepatic/renal insufficiency or mental disorder; Pregnancy or planning for pregnancy; Known allergy, or contraindication to rescue medication or related drugs; Known phobia to acupuncture or having received acupuncture treatment, or sphenopalatine ganglion stimulation or other complementary and alternative medicine within 1 months prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Participants who agreed to randomization will be allocated to the acupuncture group, sham acupuncture group or rescue medication group in a 1:1:1 ratio
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acupuncture group<br> | Other: Acupuncture group<br>* Sterile single-use stainless steel needles (size 0.35 mm × 55 mm) (YiDaiFu brand, Suzhou Tianyi Acupuncture Instrument Co., Ltd., Suzhou, China) will be utilized. Participants in lateral position, the acupoints area will be sterilized with 75% alcohol. To stimulate SPG, the needles will be inserted in the medial superior anterior direction to a depth of approximately 55 mm33 until the participants report a special sensation radiating toward the nose or the upper teeth. After that, the needle will be withdrew slightly. The needles will be retained for 30 minutes after three stimulation. Rescue medication are permitted when participants feel that their symptoms are intolerable.<br>|
| Placebo Comparator: Placebo acupuncture group<br> | Other: Placebo acupuncture group<br>* The acupuncture procedure will be similar to that of the acupuncture group. After sterilizing the skin, the 0.35 × 25 mm disposable needle will be vertically inserted at SPG acupoint about 3-5 mm. No needle manipulation will be conducted to avoid the deqi response. Rescue medication are permitted when participants feel that their symptoms are intolerable.<br>|
| Other: Rescue medication<br> | Other: Rescue medication group<br>* Participants in the rescue medication group do not receive acupuncture treatment during the study period. They will be only allowed to use rescue medication. They have the option of 4 weeks (up to 8 sessions) of acupuncture free of charge at the end of the follow-up period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline in the average daily Combined Symptoms and Medication Score (CSMS) over weeks 1- 4 | The average daily Combined Symptoms and Medication Score (CSMS) is the sum of the daily symptom score (dSS) plus daily medication score (dMS) . The dSS contains a 6-item scale referring to nasal symptoms (4 items) and ocular symptoms (2 items), with each item scored using a Likert scale of 0 to 3. The dSS will be calculated as a mean of all non-missing dSS divided by the number of individual symptoms (range, o to 3). The dMS will again be calculated as an average of daily symptom relief medication score, with a range of 0 to 3. | weeks 1-4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline in the average daily Combined Symptoms and Medication Score (CSMS) over weeks 5- 8 and the first week following symptoms onset in the second year | The average daily Combined Symptoms and Medication Score (CSMS) is the sum of the daily symptom score (dSS) plus daily medication score (dMS) . The dSS contains a 6-item scale referring to nasal symptoms (4 items) and ocular symptoms (2 items), with each item scored using a Likert scale of 0 to 3. The dSS will be calculated as a mean of all non-missing dSS divided by the number of individual symptoms (range, o to 3). The dMS will again be calculated as an average of daily symptom relief medication score, with a range of 0 to 3. | over weeks 5- 8 and the first week following symptoms onset in the second year | 
| Change in the average daily symptom score (dSS) and daily medication score (dMS) from baseline over weeks 1- 4, weeks 5-8 in the first year and the first week following symptoms onset in the second year. | The daily symptom score (dSS) contains a 6-item scale referring to nasal symptoms (4 items) and ocular symptoms (2 items), with each item scored using a Likert scale of 0 to 3. The dSS will be calculated as a mean of all non-missing dSS divided by the number of individual symptoms (range, o to 3). The daily medication score (dMS) will again be calculated as an average of daily symptom relief medication score, with a range of 0 to 3. | over weeks 1- 4, weeks 5-8 in the first year and the first week following symptoms onset in the second year. | 
| The proportion of participants with a minimum of 23% improvement in average daily Combined Symptoms and Medication Score (CSMS) from baseline over weeks 1-4, weeks 5-8 in the first year and at the first week following symptoms onset in the second year. | A difference of 23% on the average daily Combined Symptoms and Medication Score (CSMS) was chosen to demonstrate a minimum clinically important difference. | over weeks 1- 4, weeks 5-8 in the first year and the first week following symptoms onset in the second year. | 
| Change in the Rhinoconjunctivitis Quality of Life Questionnaires (RQLQ) total score and subscale scores from baseline to the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year. | The RQLQ is a well-established and validated questionnaire consisted of 28 questions covering 7 domains: sleep (3 items), practical problems (3 items), non-nasal and eye symptoms (7 items), nasal symptoms (4 items), eye symptoms (4 items), activities that have been limited by nose or eye symptoms (3 items), and emotional function (4 items). Each item will be evaluated on a 7-point rating scale ranging from 0 (no impairment) to 6 (severe impairment) during the previous week. | At the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year | 
| Change in the Visual analog scale score for the overall allergic symptoms severity from baseline to the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year. | Patients will be asked to grade the severity of allergic symptoms using the self-rated 0-100mm Visual analog scale (0, no symptoms, to 100, worst-ever symptoms, in 1-point increment). | At the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year | 
| A global evaluation in comparison to previous years by each participant at the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year. | Each participant will be asked the following question: ''Compared to your symptoms in previous grass pollen seasons, how have you felt overall in this grass pollen season? (Tick only one). The possible answers are coded as follows：1, Very much better; 2, Much better; 3, A little better; 4, No change; 5, A little worse; 6, Much worse; and 7, Very much worse. | At the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year | 
| Patient global evaluation of improvement at the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year. | Patient global evaluation of improvement will be rated by the participants using a 7-point Likert scale with the following options: 1, Very much better; 2, Much better; 3, A little better; 4, No change; 5, A little worse; 6, Much worse; and 7, Very much worse at each study visit. | At the end of weeks 4 and 8 in the first year and the first week following symptoms onset in the second year | 
| The average weekly number of medication-free days during weeks 1-4, weeks 5-8 in the first year. | The average weekly number of medication-free days during weeks 1-4, weeks 5-8 in the first year will be compared among three groups | during weeks 1-4, weeks 5-8 in the first year | 
| The average weekly number of symptom-free days during weeks 1-4, weeks 5-8 in the first year. | The average weekly number of symptom-free days during weeks 1-4, weeks 5-8 in the first year will be compared among three groups | during weeks 1-4, weeks 5-8 in the first year |