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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Procedure: SPA acupuncture; Procedure: sham acupuncture

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Hongfei Lou

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:

1. history of physician-diagnosed SAR with at least 2 years of typical symptoms, and TNSS>=6 at v0.
2. positive skin prick test (SPT) and/or positive serum antigen specific IgE to local seasonal pollens (Giant Ragweed, Mugwort, Goosefoot, etc)

Exclusion Criteria:

1. oral steroids within 4 weeks prior to recruitment
2. nasal steroids and/or antihistamine 2 weeks prior to recruitment
3. perennial AR
4. any respiratory infection within the previous 4 weeks prior to recruitment
5. history of nasal polyps, asthma or autoimmune disorders
6. previously received acupuncture therapy for AR within 1 month prior to recruitment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SPA acupuncture; active SPG acupuncture plus rescue medication (AA group)	Procedure: SPA acupuncture; 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 ).
Sham Comparator: sham acupuncture; sham-SPG acupuncture plus rescue medication (SA group)	Procedure: sham acupuncture; 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).

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital

Publications and helpful links

General Publications

• Choi SM, Park JE, Li SS, Jung H, Zi M, Kim TH, Jung S, Kim A, Shin M, Sul JU, Hong Z, Jiping Z, Lee S, Liyun H, Kang K, Baoyan L. A multicenter, randomized, controlled trial testing the effects of acupuncture on allergic rhinitis. Allergy. 2013 Mar;68(3):365-74. doi: 10.1111/all.12053. Epub 2012 Dec 18.
• Xue CC, Zhang AL, Zhang CS, DaCosta C, Story DF, Thien FC. Acupuncture for seasonal allergic rhinitis: a randomized controlled trial. Ann Allergy Asthma Immunol. 2015 Oct;115(4):317-324.e1. doi: 10.1016/j.anai.2015.05.017. Epub 2015 Jun 11.
• Brinkhaus B, Ortiz M, Witt CM, Roll S, Linde K, Pfab F, Niggemann B, Hummelsberger J, Treszl A, Ring J, Zuberbier T, Wegscheider K, Willich SN. Acupuncture in patients with seasonal allergic rhinitis: a randomized trial. Ann Intern Med. 2013 Feb 19;158(4):225-34. doi: 10.7326/0003-4819-158-4-201302190-00002.
• Wang K, Chen L, Wang Y, Wang C, Zhang L. Sphenopalatine Ganglion Acupuncture Improves Nasal Ventilation and Modulates Autonomic Nervous Activity in Healthy Volunteers: A Randomized Controlled Study. Sci Rep. 2016 Jul 18;6:29947. doi: 10.1038/srep29947.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2020
• Primary Completion (Actual): October 31, 2020
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 3, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Acupuncture; inflammatory cytokines; sphenopalatine ganglion; seasonal allergic rhinitis; neuropeptides; neuro-immune interactions
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Neoplasms; Hypersensitivity, Immediate; Cysts; Connective Tissue Diseases; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Mucinoses; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Ganglion Cysts
• Other Study ID Numbers: SPA acupuncture for SAR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No