Acupuncture for Nasal Congestion in Allergic Rhinitis: An Open-Label, Randomized, Monocenter Trial (ANCAR Trial)
Phase: NA
Conditions: Allergic Rhinitis
Sponsor: Johanna Maria Vermeulen

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
1 
 
 
 
 
 
 
RESEARCH PROTOCOL 
 
Acupuncture for Nasal Congestion 
in Allergic Rhinitis:  
An Open-Label, Randomized, 
Monocenter Trial 
(ANCAR Trial) 
 
NTC Number: NCT05709977 
 
Date: July 19, 2023 
 
Johanna Maria Vermeulen (Copyright Texts) 
PhD student Nanjing University of Chinese Medicine 
(Nanjing, China) 
 
Principal Supervisor: Professor Tianshu Xu 
Associate Supervisor: Professor Peilin Sun 
 
 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
2 
PROTOCOL TITLE  
Acupuncture for Nasal Congestion in Allergic Rhinitis: An Open-Label, Randomized, 
Monocenter Trial (ANCAR Trial) 
 
Protocol ID 
ANCAR Trial 
Short title 
Acupuncture for Nasal Congestion in Allergic Rhinitis 
(ANCAR) 
EudraCT number  
Not applicable 
Version 
6 
Date 
July 19, 2023 
Coordinating 
investigator/project leader 
Johanna Maria Vermeulen (acupuncturist, 
physiotherapist 
and owner of Mermaid Medicine®)  
Spiegelkarpersingel 13                                      
2492 NC Den Haag, Nederland                                          
Tel: 070-3694787 / 06-12609510                      
E-mail: info@mermaidmedicine.com          
Website: www.mermaidmedicine.com  
Principal investigator(s) (in 
Dutch: hoofdonderzoeker/ 
uitvoerder) 
Johanna Maria Vermeulen (acupuncturist, 
physiotherapist 
and owner of Mermaid Medicine®)  
Spiegelkarpersingel 13                                      
2492 NC Den Haag, Nederland                                          
Tel: 070-3694787 / 06-12609510                      
E-mail: info@mermaidmedicine.com           
Website: www.mermaidmedicine.com 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
Mermaid Medicine®                                      
Medische Acupunctuur - Duikgeneeskunde  
Spiegelkarpersingel 13                                      
2492 NC Den Haag, Nederland                                          
Tel: 070-3694787 / 06-12609510                      
E-mail: info@mermaidmedicine.com         
Website: www.mermaidmedicine.com 
Subsidising party 
Crowdfunding (GoFundMe), DocSave (provides free 
Cloud & Dragon® acupuncture needles, NonDolens® 
medical gloves and acuBox® needle containers); 
Nederlandse Vereniging voor Acupunctuur (NVA) will 
decide January 11, 2023 in board meeting on a possible 
sponsorship. 
Independent expert (s) 
Dr. Menno Gaastra, dermatoloog en duikerarts. 
• Noordwest Ziekenhuisgroep 
Wilhelminalaan 12 
1815 JD Alkmaar 
• Centrum Oosterwal 
Comeniusstraat 3  

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
3 
1817 MS Alkmaar 
Tel: 06-53278208 
E-mail: m.gaastra@centrum-oosterwal.nl 
Laboratory sites 
Not applicable 
Pharmacy  
Not applicable 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
4 
PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor or legal representative: 
Johanna Maria Vermeulen, 
acupuncturist,  
physiotherapist and owner of 
Mermaid Medicine®                                
 
 
July 19, 
2023 
[Coordinating Investigator/Project 
leader/Principal Investigator]: 
Johanna Maria Vermeulen, 
acupuncturist,  
physiotherapist and owner of 
Mermaid Medicine®                                
 
 
July 19, 
2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
5 
TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE 
8 
2. 
OBJECTIVES 
9 
3. 
STUDY DESIGN 
10 
4. 
STUDY POPULATION 
11 
4.1 
Population (base) 
11 
4.2 
Inclusion criteria 
11 
4.3 
Exclusion criteria 
11 
4.4 
Sample size calculation 
11 
5. 
TREATMENT OF SUBJECTS 
12 
5.1 
Investigational product/treatment 12 
5.2 
Use of co-intervention (if applicable) 
12 
5.3 
Escape medication (if applicable) 12 
6. 
INVESTIGATIONAL PRODUCT 13 
6.1 
Name and description of investigational product(s) 
13 
6.2 
Summary of findings from non-clinical studies 13 
6.3 
Summary of findings from clinical studies 
13 
6.4 
Summary of known and potential risks and benefits 
13 
6.5 
Description and justification of route of administration and dosage 13 
6.6 
Dosages, dosage modifications and method of administration 
13 
6.7 
Preparation and labelling of Investigational Medicinal Product 
13 
6.8 
Drug accountability 13 
7. 
NON-INVESTIGATIONAL PRODUCT 
14 
7.1 
Name and description of non-investigational product(s) 
14 
7.2 
Summary of findings from non-clinical studies 14 
7.3 
Summary of findings from clinical studies 
14 
7.4 
Summary of known and potential risks and benefits 
14 
7.5 
Description and justification of route of administration and dosage 14 
7.6 
Dosages, dosage modifications and method of administration 
14 
7.7 
Preparation and labelling of Non-Investigational Medicinal Product 14 
7.8 
Drug accountability 14 
8. 
METHODS 15 
8.1 
Study parameters/endpoints 
15 
8.1.1 Main study parameter/endpoint 
15 
8.1.2 Secondary study parameters/endpoints (if applicable) 15 
8.1.3 Other study parameters (if applicable) 
15 
8.2 
Randomization, blinding and treatment allocation 
15 
8.3 
Study procedures 
15 
8.4 
Withdrawal of individual subjects 15 
8.4.1 Specific criteria for withdrawal (if applicable) 
15 
8.5 
Replacement of individual subjects after withdrawal 
15 
8.6 
Follow-up of subjects withdrawn from treatment 15 
8.7 
Premature termination of the study 
15 
9. 
SAFETY REPORTING 
16 
 
16 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
6 
9.2 
AEs, SAEs and SUSARs 16 
9.2.1 Adverse events (AEs) 
16 
9.2.2 Serious adverse events (SAEs) 
16 
9.2.3 Suspected unexpected serious adverse reactions (SUSARs) 17 
9.3 
Annual safety report 18 
9.4 
Follow-up of adverse events 
19 
9.5 
[Data Safety Monitoring Board (DSMB) / Safety Committee] 19 
10. 
STATISTICAL ANALYSIS 20 
10.1 Primary study parameter(s) 
20 
10.2 Secondary study parameter(s) 
20 
10.3 Other study parameters 
20 
10.4 Interim analysis (if applicable) 
20 
11. 
ETHICAL CONSIDERATIONS 
21 
11.1 
Regulation statement 
21 
11.2 
Recruitment and consent 21 
11.3 
Objection by minors or incapacitated subjects (if applicable) 21 
11.4 
Benefits and risks assessment, group relatedness 
21 
11.5 
Compensation for injury 
21 
11.6 
Incentives (if applicable) 
22 
12. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 23 
12.1 Handling and storage of data and documents 23 
12.2 Monitoring and Quality Assurance 23 
12.3 Amendments 23 
12.4 Annual progress report 
24 
12.5 End of study report 24 
12.6 Public disclosure and publication policy 25 
13. 
STRUCTURED RISK ANALYSIS 26 
13.1 Potential issues of concern 26 
13.2 Synthesis 
27 
14. 
REFERENCES 
27 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
7 
LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
ABR 
General Assessment and Registration 
form  
(ABR form), the application form that is 
required for submission to the accredited 
Ethics Committee; in Dutch: Algemeen 
Beoordelings- en Registratieformulier 
(ABR-formulier) 
AE 
Adverse Event 
AR 
Adverse Reaction 
CA 
Competent Authority 
CCMO 
Central Committee on Research Involving  
Human Subjects; in Dutch: Centrale  
Commissie Mensgebonden Onderzoek 
CV 
Curriculum Vitae 
DSMB 
Data Safety Monitoring Board 
EU 
European Union 
EudraCT 
European drug regulatory affairs Clinical 
Trials  
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation; in 
Dutch: Algemene Verordening 
Gegevensbescherming (AVG) 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
IMP 
Investigational Medicinal Product  
IMPD 
Investigational Medicinal Product Dossier  
METC  
Medical research ethics committee 
(MREC); in Dutch: medisch-ethische 
toetsingscommissie (METC) 
(S)AE 
(Serious) Adverse Event  
SPC 
Summary of Product Characteristics; in 
Dutch: officiële productinformatie IB1-
tekst 
Sponsor 
The sponsor is the party that 
commissions the organisation or 
performance of the research,  
for example a pharmaceutical 
company, academic hospital, scientific 
organisation or investigator. A party that  
provides funding for a study but does not 
commission it is not regarded as the 
sponsor,  
but referred to as a subsidising party. 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
8 
SUSAR  
Suspected Unexpected Serious Adverse  
Reaction 
UAVG 
Dutch Act on Implementation of the 
General  
Data Protection Regulation; in Dutch: 
Uitvoeringswet AVG 
WMO 
Medical Research Involving Human 
Subjects  
Act; in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
9 
SUMMARY   
Rationale: Allergic rhinitis (AR) is a disorder that affects more than 500 million people 
worldwide. Nasal congestion is one the most general and bothersome symptoms in 
rhinitis, which affects the quality of life (QOL). Current medications are undesirable due 
to their side-effects. Acupuncture for AR in general can be considered as safe and can 
be seen as a potential remedial blueprint for nasal congestion. Evidence supported that 
acupuncture is clinically used for signs and symptoms of nose disorders, such as nasal 
congestion, with effectiveness, but whether acupuncture has immediate, post-treatment 
and long-term effects on specifically nasal congestion in AR is not verified by strictly 
designed clinical study. The ANCAR trial uses a standard treatment protocol with a fixed 
set of acupuncture points - to be as scientific as possible from Western viewpoint - to 
open the nose and affect underlying energetic imbalance and immunity at the same 
time, to maintain its nose opening effect. This novel acupuncture treatment protocol can 
be seen as a solid and profound approach from which every AR patient may benefit.            
Hypothesis: Acupuncture will improve nasal congestion in AR compare to azelastine 
nasal spray (Carelastin®). 
Objective: To evaluate the effects of an acupuncture treatment protocol for nasal 
congestion in AR.   
Study design: An open-label, randomized, monocenter trial. 
Study population: Adult patients with AR sent to Mermaid Medicine® in The Hague, the 
Netherlands. 
Intervention: The acupuncture arm will receive a fixed set of acupuncture points during 
6 weeks: 2 treatments per week in the first 2 weeks and 1 treatment per week in the 
consecutive 4 weeks (10 acupuncture points with totally 17 needles per treatment). The 
control arm will receive Carelastin® azelastine nasal spray (1mg/1ml), 1 spray puff (0.14 
ml) per nostril twice daily (0.56 mg totally per patient per day) during 6 weeks. 
Main study parameters/endpoints: VAS, Adapted NOSE and PNIF. 
Nature and extent of the burden and risks associated with participation, benefit 
and group relatedness: Negligible risk. 
 
 
 
 
 
 
 
 
 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
10 
1.        INTRODUCTION AND RATIONALE 
Worldwide more than approximately 500 million people suffer from AR[1, 2] (30% of the 
Dutch population (Mylan Update, 2018[2]) and its prevalence is expanding[1]. Nasal 
congestion (i.e. reversible mucosal congestion [3]/nasal mucosal obstruction[4]) is one of 
the most general and bothersome symptoms in rhinitis[5, 6] and is associated with other 
medical conditions such as rhinosinusitis and otitis media[7, 8]. This study is relevant as 
in addition to the high global occurrence of AR, this disorder has substantial effects on 
the quality of life (QOL) (e.g. during sleep and work)[9]. AR is related to high direct 
medical costs (mainly prescription of medications and outpatient visits) and indirect 
economic costs (including productivity decrease)[8, 10, 11]. Current medications are 
undesirable due to their side-effects (such as sedation in the case of intranasal 
antihistamines (INAH)[11]).      
Acupuncture for AR in general can be considered as safe and can be seen as a 
potential remedial blueprint for nasal congestion[12]. Evidence supported that 
acupuncture is clinically used for signs and symptoms of nose disorders, such as nasal 
congestion, with effectiveness, but whether acupuncture has immediate, post-treatment 
and long-term effects on specifically nasal congestion in AR is not verified by strictly 
designed clinical study.      
The ANCAR trial aims to evaluate the effects of an acupuncture treatment protocol for 
nasal congestion in AR compare to azelastine nasal spray. A standard treatment 
protocol with a fixed set of acupuncture points has been established - to be as scientific 
as possible from Western medical viewpoint - and this selection of acupuncture points 
can be seen as a solid and profound approach from which every AR patient may 
benefit. This standard set opens the nose and affects the underlying energetic 
imbalance and immunity at the same time to maintain its nose opening effect (i.e. to 
prevent recurrence of the complaint).  
The acupuncture protocol concerns 8 treatments during 6 weeks (i.e. 2 treatments per 
week during the first 2 weeks and 1 treatment per week in the consecutive 4 weeks).  
The positive effects of this treatment protocol (such as improvement QOL), may result in 
more confidence in the direct, post-treatment and long-term effects of acupuncture and 
lead to more acceptance of acupuncture as a solid treatment option for nasal 
congestion in AR instead of using an INAH spray. 
 
Hypothesis: Acupuncture will improve nasal congestion in AR compare to azelastine 
nasal spray (Carelastin®).   
  
2.        OBJECTIVES 
Primary Objective:  
• To compare the effects of acupuncture with azelastine nasal spray (Carelastin®) 
on nasal congestion in AR based on VAS (Visual Analog Scale) score. 
   
Secondary Objectives:  
• To compare the effects of acupuncture with azelastine nasal spray (Carelastin®) 
on nasal congestion in AR. 
• To assess the effects of acupuncture on other nasal and ocular signs and 
symptoms in AR.  

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
11 
• To assess the effects of acupuncture on general health, concentration and 
energy level in AR. 
• To assess the effects of acupuncture on equalization of middle ear pressure in 
AR in the case patients fly and/or dive. 
 
Primary endpoint:  
• To compare the effects of acupuncture and azelastine nasal spray (Carelastin®) 
on nasal congestion in AR after 6 weeks of treatments based on VAS score (VAS 
questionnaire, Part A, question 1: Nasal congestion: see Appendix I). The VAS 
improvement score will be compared between two arms, improvement defined as 
any decrease in VAS score at 6 weeks of treatments compared to the 
corresponding entry VAS score (before starting treatment). VAS, 0 = no nasal 
congestion, and 10 = most severe nasal congestion. 
 
Secondary endpoints:  
• To compare the effects of acupuncture and azelastine nasal spray (Carelastin®) 
on nasal congestion in AR after different visits of treatments based on VAS, 
Adapted NOSE (Nasal Obstruction Symptom Evaluation (see Appendix II, part 
A)) and PNIF (Peak Nasal Inspiratory Flow) scores (PNIF: per clinical evaluation, 
3 consecutive measurements are done to calculate the mean). 
A PNIF meter (In-Check™) is used from GM Instruments® (measures nasal 
airflow during maximal inspiration with score ranges between 30 – 370 L/min) 
together with Intersurgical® masks (size Medium). The accuracy of the PNIF 
meter is: 10% or ±10 L/min. Measuring: the PNIF test should be repeated 3 
times and the highest score should be recorded in the patient’s medical file. The 
PNIF meter is an inexpensive portable tool that estimates nasal congestion 
accurately and can be used to assess AR[13]  
           The PNIF measurements procedure is as follows (according In-Check™  
           manual): 
           - The patient will receive a face mask and the mouth must be closed.  
           - In the case the patient wears glasses, they must be removed.  
           - The patient is asked to: - exhale fully 
                                                    - hold the PNIF meter horizontally, and insure the  
                                                      mask forms an airtight seal around the nose 
                                                    - inhale forcibly through the nose (about 1 second  
                                                      duration).  
• To assess the effects of acupuncture on other nasal and ocular signs and 
symptoms in AR based on VAS score (see Appendix I, part A-B). 
• To assess the effects of acupuncture on general health, concentration and 
energy level in AR after different visits of treatments based on Adapted NOSE 
score (see Appendix II, part B). 
• To assess the effects of acupuncture on equalization of middle ear pressure in 
AR in the case patients fly and/or dive after different visits of treatments based on 
Adapted NOSE score (see Appendix II, part C). 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
12 
3. 
STUDY DESIGN 
• The trial is designed as an open-label, randomized, monocenter trial. All eligible 
patients will be randomized (1:1) between two arms (parallel assignment), i.e., 
arm A (Acupuncture) and arm B (Control [Carelastin®]). 
• Short-Term-Intervention RCT: 6 weeks treatment protocol with measurements 
before and at 15 minutes after the 1st acupuncture treatment/1st azelastine 
usage (to compare the immediate effects), at 15 minutes after the 2nd - 
8th acupuncture treatment and final usage of azelastine (= parallel to 8th 
acupuncture treatment = to compare the post-treatment effects), then 
following the treatment period after 2 weeks and 2 months (to compare the long-
term effects). The accrual expected to be 60 days.  
 
4. 
STUDY POPULATION 
4.1 
Population (base) 
• Patients with AR that are sent to/visit Mermaid Medicine® during the recruitment 
(expected to be 60 days). 
 
4.2 
Inclusion criteria.  
In order to be eligible to participate in this study, a subject must meet all of the following 
criteria: 
• Diagnosed AR by a physician. 
• Have one of the AR types: seasonal (SAR) or perennial (PAR) or mixed (MAR) 
allergic rhinitis. 
• VAS nasal congestion: from 3-10. 
• Age: from 18 years.  
• Signed Informed Consent. 
 
Figure 4.2.1 VAS for the degree of nasal congestion[14, 15] (and other nasal and 
                     ocular signs and symptoms) 
 
 
 
VAS of 0 = no nasal congestion, and 10 = most severe nasal congestion. 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
13 
4.3 
Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from 
participation in this study: 
• COVID-19.  
• Acute common cold.  
• Influenza. 
• Fever (38°C or higher). 
• Acute nasal trauma (such as a fracture and epistaxis). 
• Irreversible nasal blockages (such as septum deviation, concha bullosa, polyps 
and cysts). 
• Nasal and sinus cancer. 
• Pregnancy or planning for pregnancy. 
• Consumed decongestions, antihistamines, antibiotics or corticosteroids within 2 
weeks before the RCT. 
• Received acupuncture, Chinese herbal medicine or another complementary 
treatment within 2 weeks before the RCT. 
• Received immunotherapy within 2 weeks before the RCT. 
• Patients refusing or unable to sign Informed Consent. 
 
4.4 
Sample size calculation 
East version 6.5 is used to calculate the sample size. The sample size is based on two 
independent study arms and the primary endpoint is dichotomous (yes/no).  
Arm A has an incidence of 51.3% based on total nasal symptom score (TNNS) post-
treatment of a SAR study from Xue et al. (2002, TNSS post-treatment of 66.3%) and a 
PAR study from Xue et al. (2007, TNSS post-treatment of 36.3%)[16,17]. No exact 
information about nasal congestion of the SAR (2002) study is available and therefore 
the TNSS is used to calculate the sample size for the ANCAR trial. The use of 
azelastine (1 mg/ml, 1 spray of 14 mg in each nostril twice daily) in SAR has 14.1% and 
22.1% improvement for the TNSS in respectively study 1 and study 2 from Lumry 
(2007)[18], which results in a mean of 18.1% (= incidence arm B). There is no major 
difference between TNSS and VAS (there is a high correlation between TNSS and 
VAS). By estimating an incidence of 51.3% for arm A and the incidence of 18.1% for 
arm B - to compare these proportions and detect a difference with an alpha 0.05 two-
tailed test, and a 80% statistical power - in total 62 patients (1:1 randomization) will be 
needed. 
 
Sample size 
 
Arm A (Acupuncture) 
Number dependent on randomization 
Arm B (Control) 
Number dependent on randomization 
Total  
62 
 
 
 
 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
14 
Study parameters 
 
Incidence, arm A 
51.3% 
Incidence, arm B 
18.1% 
Alpha  
0.05 
Betha 
0.2 
Power 
80% 
 
5. 
TREATMENT OF SUBJECTS 
5.1 
Investigational product/treatment 
Acupuncture (Arm A) 
A fixed set of acupuncture points is used for every patient. The RCT treatment concerns 
10 acupuncture points per treatment (= totally 17 needles per treatment).  
In total 8 acupuncture treatments: 2 treatments per week during the first 2 weeks and 1 
treatment per week in the consecutive 4 weeks. 
 
LI-20 (Yingxiang -) bilateral, Bitong (M-HN-14 -) bilateral, Yintang (M-HN-3 -) on midline 
body, GV-23 (Shangxing -) on midline body, LI-4 (Hegu -) bilateral, LU-7 (Lieque -) 
bilateral, CV-6 (Qihai +) on midline body, ST-36 (Zusanli +) bilateral, SP-6 (Sanyinjiao 
+) bilateral, Ear: Allergy Point (-) bilateral.  
 
+ = Tonifying needling technique, - = Reducing needling technique 
 
Needles  
• Standard disposable sterile acupuncture needles.  
• Brand needles: Cloud & Dragon (DocSave.com).  
• Needle sizes: on the face: size: 0.22 x 25 mm, on the belly and limbs: 0.25 x 40 
mm, for Ear Apex Allergy Point: 0.22 x 15 mm. 
 
Needling Specifications 
• Needling time: 30 minutes. 
• Needle sensation (Deqi). Deqi is defined (according the latest Chinese-English 
Dictionary of Traditional Chinese Medicine (TCM)[19][pp.877-878]) as ‘needling 
sensation, which refers to the patient's response to sore, numb, distention, 
electric shock and the doctor's heavy and tight sensation coming from beneath 
the needle’. 
 
Azelastine Nasal Spray (Arm B) 
Carelastin® is used with the conventional dosage (= most generally recommended 
dosage):  
1 spray puff per nostril twice daily[18]. 1 spray puff (0.14 ml) of Carelastin® (1 mg/ml) 
contains 0.14 mg (137 mcg) azelastine hydrochloride (0.56 mg totally per patient per 
day). 
 
5.2 
Use of co-intervention (if applicable) 
• Acupuncture arm: No oral or intranasal decongestions, antihistamines or 
corticosteroids. 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
15 
• Azelastine arm: No other INAH, no oral antihistamines and no oral or intranasal 
decongestions or corticosteroids. 
 
5.3 
Escape medication (if applicable) 
Not applicable. 
 
6. 
INVESTIGATIONAL PRODUCT  
6.1 
Name and description of investigational product(s)/treatment 
• Acupuncture. 
 
6.2 
Summary of findings from non-clinical studies 
Not applicable. 
 
6.3 
Summary of findings from clinical studies 
Acupuncture can be seen as a potential remedial blueprint for nasal congestion, 
especially in the case of non-efficacy, drug resistance or atrophic rhinitis[12].  
Acupuncture could be a valid and effective treatment option for signs and symptoms of 
AR[20,21] with an efficacious improvement of QOL[21]. However: a standard treatment 
protocol and a standardized scoring system (high-quality research[22]) are missing[20]. 
The ANCAR trial - consisting of a complete, compact and fixed set of acupuncture 
points - may contribute to a clear and effective treatment protocol for nasal congestion 
in AR.       
 
Clinical note: Additional information regarding the efficacy of acupuncture for complaints  
                      of allergic rhinitis, which substantiates the statements in this summary, is  
                      added as Appendix IV. 
 
6.4 
Summary of known and potential risks and benefits 
Acupuncture for AR in general can be considered as safe[20,21]. No fatal or serious 
events are reported[20,21], solely mild side-effects such as pain, papules, pruritus, 
subcutaneous hematomas, dizziness, numbness and headache[20].  
Benefits: acupuncture can reduce signs and symptoms of AR[20, 21], has the possibility to 
boost blood rheology indexes with an increased volume of blood circulation and 
regulation of immunity[23] besides that there is evidence of reduction of the plasmatic 
level of IL-10 in chronic AR patients[24], efficacious improvement QOL[21]. 
 
6.5 
Description and justification of route of administration and dosage 
• 8 acupuncture treatments during 6 weeks. 2 treatments per week in the first 2 
weeks and 1 treatment per week in the consecutive 4 weeks. 
• Needling retention time: 30 minutes.  
• Needling depth: It needs to meet the requirements of acupuncture theory, human 
physiology and individual difference (the different acupuncture points require 
different needling depth).      
 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
16 
6.6 
Dosages, dosage modifications and method of administration 
• Reducing needling technique is used for: LI-20 (Yingxiang), Bitong (M-HN-14), 
Yintang (M-HN-3), GV-23 (Shangxing), LI-4 (Hegu ), LU-7 (Lieque ) and Ear: Allergy 
Point.  
• Tonifying needling technique is used for: CV-6 (Qihai), ST-36 (Zusanli) and SP-6 
(Sanyinjiao). 
 
Table 6.6 Needling techniques[25][p.40] 
Reinforcing (Tonifying/+) Method             Reducing (Sedating/-) Method 
Lifting and thrusting:  
Lifting the needle gently and slowly; 
thrusting heavily and rapidly 
Lifting and thrusting: 
Lifting the needle forcefully and rapidly; 
thrusting gently and slowly 
Twirling and rotating: 
Rotating gently and slowly with small 
amplitude 
Twirling and rotating: 
Rotating rapidly with large amplitude 
Rotating direction:  
Clockwise 
Rotating direction:  
Counter-clockwise 
Insertion:  
Slow 
Insertion:  
Rapid 
Withdrawal:  
Rapid 
Withdrawal:  
Slow 
Direction tip of the needle:  
Following the direction of the course of 
the channel 
Direction tip of the needle:  
Against the direction of the course of the 
channel 
Keeping the hole open or closed:  
Press the hole rapidly  
(to prevent that Qi escapes) 
Keeping the hole open or closed: 
Shake it to enlarge the hole  
(to drive out Xie Qi) 
Respiration:  
Inserting the needle when the patient 
breathes out, withdrawing when breathing 
in 
Respiration:  
Inserting the needle when the patient 
breathes in, withdrawing when breathing 
out 
 
6.7 
Preparation and labelling of Investigational Medicinal Product 
     Not applicable. 
 
6.8 
Drug accountability 
Not applicable. 
7. 
NON-INVESTIGATIONAL PRODUCT 
7.1 
Name and description of non-investigational product(s) 
• Carelastin® nasal spray (1 mg/ml). 
 
7.2 
Summary of findings from non-clinical studies 
Not applicable. 
 
7.3 
Summary of findings from clinical studies 
• Azelastine nasal spray (0.1%) monotherapy has clinical efficacy for treating AR 
that is equal or superior to oral second-generation antihistamine, has a clinically 
significant effect on nasal congestion[26,27,28] and can be used on an as needed 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
17 
basis compare to INCS that need to be taken before the symptoms start to 
benefit optimally from its effects[28]. Intranasal antihistamines (INAH) have a quicker 
onset of action compare to intranasal corticosteroids (INCS)[29](e.g. azelastine nasal 
spray tested superior to mometasone nasal spray[30]). 
• Azelastine nasal spray is also approved for non-allergic rhinitis (NAR)[26] and 
equally effective (with 2 sprays per nostril twice daily, 1.1 mg/day) as the 
combination therapy of oral loratadine (Claritin®, one 10-mg tablet/day) and 
intranasal beclomethasone (INCS) (i.e. Beconase AQ®, 2 sprays per nostril twice 
daily, 336 mcg/day) treating moderate to severe SAR (both early-phase and late-
phase signs and symptoms)[27].  
• Azelastine nasal spray (1 spray puff per nostril twice daily (= totally 0.28 mg per 
nostril/day)) is effective and has better tolerability compared to 2 sprays per 
nostril twice daily (= totally 0.56 mg per nostril/day) in moderate-severe SAR 
patients[18] and has been proved effective and safe in the treatment of moderate-
severe PAR[31]. 
• Globally, azelastine nasal spray is approved for SAR and PAR treatment in more 
than 80 countries[18]. 
 
7.4 
Summary of known and potential risks and benefits 
• Side-effects: bitter taste, drowsiness[11, 27], headache and nasal burning[27].   
• Benefits: quick onset of action: at 15 minutes in SAR[32] and PAR[31] and last up 
to 4 hours[33]/12 hours[34]. 
 
7.5 
Description and justification of route of administration and dosage 
• 1 spray puff (0.14 ml) of Carelastin® (1 mg/ml) contains 0.14 mg (137 mcg) 
azelastine hydrochloride. 1 spray puff per nostril twice daily (totally 0.28 mg per 
nostril / total dosage of 0.56 mg per day) is the conventional (= most generally 
recommended) dosage for AR and is effective and has better tolerability 
compared to 2 spray puffs twice daily (totally 0.56 ml per nostril) in moderate-
severe SAR patients[18] and has been proved effective and safe in the treatment 
of Chinese patients with moderate-severe PAR[31]. 
 
7.6 
Dosages, dosage modifications and method of administration 
• Dosages, dosage modifications: 1 spray puff in each nostril twice daily. 
• Method of administration: Spray (with pump) 
o When using the spray for the first time, you have to press the pump a few 
times until a fine mist comes out. The spray chamber then can fill with the 
solution. The next time this is no longer necessary. 
o Blow the nose beforehand. 
o Shake the bottle several times to mix the contents. 
o Keep your head upright, insert the tip of the nose piece into one nostril, 
keep the other nostril closed and press the pump once. Sniff the liquid 
simultaneously so that the medicine enters deep into the nose. 
o Do not swallow the excess mucus, but spit it out. 
o Rinse and dry the spray head after use. 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
18 
7.7 
Preparation and labelling of Non-Investigational Medicinal Product 
• Original Carelastin® nasal spray. 
 
7.8 
Drug accountability 
Not applicable. 
 
 
8. METHODS 
8.1 
Study parameters/endpoints 
8.1.1 Main study parameter/endpoint 
• VAS to compare the effects of acupuncture with azelastine nasal spray 
(Carelastin®) on nasal congestion in AR after 6 weeks of treatments (VAS, 0 = 
no nasal congestion, and 10 = most severe nasal congestion). The VAS score 
improvement defined as any decrease in VAS score at 6 weeks of treatments 
compared to entry VAS score (before starting treatment).  
 
8.1.2 Secondary study parameters/endpoints (if applicable) 
• Adapted NOSE and PNIF to compare the effects of acupuncture with azelastine 
nasal spray (Carelastin®) on nasal congestion in AR after different visits of 
treatments. In terms of improvement and the quantity of improvement. 
• VAS to assess the effects of acupuncture on other nasal and ocular signs and 
symptoms in AR (sneezing, nasal itching, rhinorrhea, itchy eyes, red eyes, 
burning eyes and watery eyes). 
• Adapted NOSE with novel additions regarding general health, concentration, 
energy level and ear pressure equalization in diving and flying. 
 
8.1.3 Other study parameters (if applicable) 
Not applicable. 
 
8.2 
Randomization, blinding and treatment allocation 
• The 1:1 randomization to arm A and B with block randomization size of 2 and 4 
will be done by an independent statistician via a computer program (R program 
language blockrand package). The 62 randomly generated treatment allocations 
will be sent in advance within sealed opaque envelopes to the Mermaid Medicine 
site. Once a patient has consented to enter the trial, and after controlling the 
eligibility criteria the assigned envelope will be opened and the patient is then 
offered the allocated treatment regimen. 
 
8.3 
Study procedures 
Time of clinical evaluations 
• T0: 
At entry: Controlling the eligibility of patients by including and excluding criteria. 
Providing information, Informed Consent and taking medical history (health 
profile including TCM pulse and tongue diagnosis). After patient inclusion the 
patient will be assigned to the randomly assigned arm.    
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
19 
• T1:  
T1_1 = Before 1st acupuncture treatment/1st usage of Carelastin® azelastine 
nasal spray (VAS, Adapted NOSE, PNIF). 
T1_2 = At 15 minutes after 1st acupuncture treatment/1st usage of Carelastin® 
azelastine nasal spray (VAS, PNIF, adverse effects (AEs), remarks patient). 
 
• T2: 
Only for arm A: At 15 minutes after acupuncture treatments 2-7 (VAS, AEs, 
remarks patient).  
 
• T3: Primary endpoint 
At 15 minutes after acupuncture treatment 8/final usage Carelastin® azelastine 
nasal spray (VAS, Adapted NOSE, PNIF, AEs, remarks patient). 
 
• T4: 
After 2 weeks after the 6 weeks treatment protocol (for both arms): VAS, PNIF, 
AEs, remarks patient. 
 
• T5: 
After 2 months after the 6 weeks treatment protocol (for both arms): VAS, Adapted 
NOSE, PNIF, AEs, remarks patient. 
 
All patients will be followed until 2 months after registration and at every visit if the 
patient has COVID-19, the common cold, influenza, fever or suspected to have COVID-
19, the common cold or influenza, the visit will be postponed and this will be considered 
as protocol violation.  

 
Copyright Texts Johanna Maria Vermeulen, 2023 
20 
Table. Details Timeline of the ANCAR trial 
 
 
T0 At 
entry 
T1_1 
T1_2 
T2 
Only for arm A  
(Acupuncture 
2:7) 
T3 
Primary 
endpoint 
(end of 
treatment) 
T4 
2 weeks 
follow UP 
T5 
2 months 
follow UP 
Inclusion and 
exclusion criteria 
X 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
TCM pulse and 
tongue diagnosis 
X 
 
 
 
 
 
 
VAS 
 
X1 
X1 
X1, 2 
X1 
X1 
X1 
Adapted NOSE 
 
X 
 
 
X 
 
X 
PNIF 
 
X 
X 
 
X 
X 
X 
Adverse events 
(AEs) 
 
 
X 
X2 
X 
X 
X 
Remarks patient 
 
 
X 
X2 
X 
X 
X 
 
1 At every visit the patient will be asked/examined for having COVID-19, the common cold, influenza, or fever. In case of positive result, the visit   
  will be postponed. 
2 Only for arm A at 15 minutes after Acupuncture visits 2 till 7. 
 
 
 

 
Copyright Texts Johanna Maria Vermeulen, 2023 
21 
8.4 
Withdrawal of individual subjects 
Subjects can leave the study at any time for any reason if they wish to do so without any 
consequences. The investigator can decide to withdraw a subject from the study for 
urgent medical reasons or pregnancy. 
If the patient has COVID-19, the common cold, influenza, fever or suspected to have 
COVID-19, the common cold or influenza, the visit will be postponed.  
 
8.4.1 Specific criteria for withdrawal (if applicable) 
• The patient is sick and can’t come to Mermaid Medicine to participate the 
ANCAR trial. 
• The patient does not want to participate the ANCAR trial anymore. 
• The patient does not feel well during the treatment and does not finish the 
ANCAR trial. 
• The patient moves away during the ANCAR trial. 
 
8.5 
Replacement of individual subjects after withdrawal 
Not applicable. The trial will be performed based on ITT principle.  
 
8.6 
Follow-up of subjects withdrawn from treatment 
Withdrawn patient will be considered as failure for primary endpoint and won’t be 
followed up further. 
 
8.7 
Premature termination of the study 
The study might be prematurely terminated based on the following criteria:  
• There is evidence of an unacceptable risk for study patients (i.e. safety issue). 
• There is reason to conclude that it will not be possible to collect the data 
necessary to reach the study objectives and it is therefore not ethical to continue 
enrollment of more patients (for example insufficient enrollment that cannot be 
improved). 
 
 
9.SAFETY REPORTING 
9.1 
Temporary halt for reasons of subject safety 
In accordance to section 10, subsection 4, of the WMO, the sponsor will suspend the 
study if there is sufficient ground that continuation of the study will jeopardise subject 
health or safety.  The sponsor will notify the accredited METC without undue delay of a 
temporary halt including the reason for such an action. The study will be suspended 
pending a further positive decision by the accredited METC. The investigator will take 
care that all subjects are kept informed.   
 
9.2 
AEs, SAEs and SUSARs 
9.2.1 Adverse events (AEs) 
• Adverse events are defined as any undesirable experience occurring to a subject 
during the study, whether or not considered related to [the investigational product 
/ trial procedure/ the experimental intervention]. All adverse events reported 
spontaneously by the subject or observed by the investigator or his staff will be 
recorded. 

 
Copyright Texts Johanna Maria Vermeulen, 2023 
22 
• All adverse events will be reported. 
 
9.2.2 Serious adverse events (SAEs). 
• No serious adverse events are expected with the use of azelastine and 
acupuncture. 
• Adverse events of azelastine: bitter taste, drowsiness[11, 27], headache and nasal 
burning[27]. 
• Acupuncture for AR in general can be considered as safe[20][21]. No fatal or 
serious events are reported[20,21[], solely mild side effects such as pain, papules, 
pruritus, subcutaneous hematomas, dizziness, numbness and headache[20]. 
 
9.2.3 Suspected unexpected serious adverse reactions (SUSARs) 
Not applicable. 
 
9.3 
Annual safety report 
Not applicable. 
 
9.4 
Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been 
reached. Depending on the event, follow up may require additional tests or medical 
procedures as indicated, and/or referral to the general physician or a medical specialist. 
SAEs need to be reported till end of study within the Netherlands, as defined in the 
protocol  
 
9.5 
Data Safety Monitoring Board (DSMB) / Safety Committee 
Not applicable. 
 
10. 
STATISTICAL ANALYSIS 
All main analyses will be according the intention to treat (ITT) principle. Patients will be 
analyzed according to the treatment arm they were assigned/randomized to. 
The formal test for difference between the two treatment arms will be done with the two-
sample proportions test. Patients who achieve a response after 6 weeks will be 
considered as a success. All other patients will be considered as a failure, including 
patients going off protocol before evaluation (6 weeks) whatever the cause. Besides we 
will calculate the proportion difference and its 95% confidence interval. This analysis will 
not be performed when the data have been validated. 
In the final analysis:  
− Missing values will not be imputed;  
− Discrete variables will be tabulated as numbers and percentages;  
− Continuous variables will be summarized using mean+standard deviation (SD),  
   median, inter-quartile range (IQR), range, number non-missing;  
− If applicable, 95% confidence intervals (CIs) will be reported;  
A separated statistical analysis plan (SAP) will be provided to describe all analyses in 
details. 
 
 

 
Copyright Texts Johanna Maria Vermeulen, 2023 
23 
10.1 Primary study parameter(s) 
• The VAS improvement score will be compared between two arms, improvement 
defined as any decrease in VAS score at 6 weeks of treatments compared to 
entry VAS score (before starting treatment). (VAS, 0 = no nasal congestion, and 
10 = most severe nasal congestion) 
 
10.2 Secondary study parameter(s)  
• The VAS, PNIF and Adapted NOSE scale improvement score will be assessed at 
different visits as described in the table of timeline.  
 
10.3 Other study parameters 
• The effects of acupuncture on other nasal and ocular signs and symptoms, on 
general health, concentration and energy level, and equalization of middle ear 
pressure in AR will be assessed at different visits as described in the table of 
timeline. 
  
10.4 Interim analysis (if applicable) 
Not applicable. No interim analysis has been designed.  
 
11. 
ETHICAL CONSIDERATIONS 
11.1 
Regulation statement 
The ANCAR trial will be conducted according to the principles of the Declaration of 
Helsinki of 1975 (version 9, July 9, 2018) and in accordance with the Medical Research 
Involving Human Subjects Act (WMO). 
 
11.2 
Recruitment and consent 
Patients will be recruited by sending emails to practices of general practitioners, besides 
ENT physicians and allergists in hospitals in the direct surroundings of Mermaid 
Medicine in Den Haag, the Netherlands. The patients will have 1 week to decide if they 
want to participate the ANCAR Trial.  
 
11.3 
Objection by minors or incapacitated subjects (if applicable) 
Not applicable. 
 
11.4 
Benefits and risks assessment, group relatedness 
Participation in the study has a negligible risk. Acupuncture for AR in general can be 
considered as safe[20,21]. No fatal or serious events are reported[20,21], solely mild side-
effects such as pain, papules, pruritus, subcutaneous hematomas, dizziness, numbness 
and headache[20].  
Side-effects Carelastin® azelastine nasal spray: bitter taste, drowsiness[11, 27], headache 
and burning sensation in the nose[27]. 
Benefits: Acupuncture and Carelastin® azelastine nasal spray can reduce AR 
symptoms.  
 
 
 

 
Copyright Texts Johanna Maria Vermeulen, 2023 
24 
11.5 
Compensation for injury 
A request for an insurance waiver is included (test subject insurance).  
Mermaid Medicine®/Johanna Maria Vermeulen has a professional liability insurance 
paramedics with the VvAA (policy number 11859873).  
 
11.6 
Incentives (if applicable) 
During the ANCAR trial, patients in arm A will receive 8 acupuncture treatments and 
patients in arm B will get 2 Carelastin® nasal sprays. All treatment will be given to 
patients free of charge. If the results are positive (arm A is superior vs arm B), the 
patients in arm B also will receive discounts on 8 acupuncture treatments (25 € discount 
per session) at Mermaid Medicine during 1 year after the ANCAR trial. The patients from 
arm B must complete the 6-weeks treatment protocol and follow-up measurements to 
receive this discount.   
 
12. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
12.1 Handling and storage of data and documents 
Data will be stored in Excel file on laptop from the sponsor/researcher. The results of 
the ANCAR trial will be shared safely with dr. Kazem Nasserinejad, statistician, who will 
analyze the results of this RCT. No other people or NJUCM will get this information.  
The contact details of dr. Kazem Nasserinejad: 
Phone: +31 (0) 64 2422405. 
E-mail: info@consultistics.nl. 
Website: https://www.consultistics.nl/.  
 
12.2 Monitoring and Quality Assurance  
Not applicable. 
 
12.3 Amendments  
Amendments are changes made to the research after a favourable opinion by the 
accredited METC has been given. All amendments will be notified to the METC that 
gave a favourable opinion.  
 
12.4 Annual progress report 
The sponsor/investigator will submit a summary of the progress of the trial to the 
accredited METC once a year. Information will be provided on the date of inclusion of 
the first subject, numbers of subjects included and numbers of subjects that have 
completed the trial, serious adverse events/ serious adverse reactions, other problems, 
and amendments.  
 
12.5 Temporary halt and (prematurely) end of study report 
The investigator/sponsor will notify the accredited METC of the end of the study within a 
period of 8 weeks. The end of the study is defined as the last patient’s last visit.  
The sponsor will notify the METC immediately of a temporary halt of the study, including 
the reason of such an action.  
    

 
Copyright Texts Johanna Maria Vermeulen, 2023 
25 
In case the study is ended prematurely, the sponsor will notify the accredited METC 
within 15 days, including the reasons for the premature termination.   Within one year 
after the end of the study, the investigator/sponsor will submit a final study report with 
the results of the study, including any publications/abstracts of the study, to the 
accredited METC.  
  
12.6 Public disclosure and publication policy 
The sponsor is the investigator. 
 
13. 
STRUCTURED RISK ANALYSIS  
13.1 Potential issues of concern 
See mentioned above (9.2.2) adverse events of azelastine nasal spray. Azelastine nasal 
spray is investigated and well-known already. 
a. Level of knowledge about mechanism of action 
Not applicable. 
 
b. Previous exposure of human beings with the test product(s) and/or products with a 
similar biological mechanism 
Not applicable. 
 
c. Can the primary or secondary mechanism be induced in animals and/or in ex-vivo 
human cell material? 
Not applicable. 
 
d. Selectivity of the mechanism to target tissue in animals and/or human beings 
Not applicable. 
 
e. Analysis of potential effect 
Not applicable. 
 
f. Pharmacokinetic considerations 
Not applicable. 
 
g. Study population 
    Not applicable. 
 
h. Interaction with other products 
Not applicable. 
 
i. Predictability of effect 
Not applicable. 
 
j. Can effects be managed? 
   Not applicable. 
 
 

 
Copyright Texts Johanna Maria Vermeulen, 2023 
26 
13.2 Synthesis 
Not applicable. 
 
 
 

Appendix I: VAS – Score 
Copyright Texts Johanna Maria Vermeulen, 2023 
27 
14.  
Appendixes 
 
VAS – Score ‘Acupuncture for Nasal Congestion in Allergic Rhinitis’ – 2022 
                       ‘Acupunctuur voor Verstopte Neus bij Allergische Rhinitis’ – 2022     
 
Date: 
Date: 
 
Participant number: 
Deelnemersnummer: 
  
Ø To the participant: Please help us to better understand the severity of your 
nasal and ocular symptoms by completing the following survey (parts A 
and B).  
Thank you! 
Aan de deelnemer: Help ons a.u.b. om de ernst van uw neus- en oogsymptomen 
            beter te begrijpen door de volgende vragenlijst (delen A en B) in te vullen.  
            Dank u wel!  
 
A.) Nasal Symptoms  
      Neussymptomen  
 
Please circle the number between 0 and 10 that describes your symptom. 
Omcirkel alstublieft het getal tussen 0 en 10 dat uw symptoom omschrijft. 
 
0 = No symptom (e.g. no nasal congestion).   
       Geen symptoom (bijv. geen verstopte neus). 
 
10 = Most severe symptom (e.g. most severe nasal congestion)   
        Meest ernstige symptoom (bijv. meest ernstige verstopte neus). 
 
 

Appendix I: VAS – Score 
Copyright Texts Johanna Maria Vermeulen, 2023 
28 
 
 
1. Nasal Symptoms 
    Neussymptomen 
 
 
No 
symptom 
Geen 
symptoom 
 
 
 
 
 
 
 
 
 
Most 
severe 
symptom 
Meest 
ernstige 
symptoom 
Nasal 
congestion  
Verstopte 
neus  
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
Sneezing 
Niezen 
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
Nasal 
itching 
Jeukende 
neus 
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
Rhinorrhea 
Loopneus 
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
 
 
 
 
 
 
 

Appendix I: VAS – Score 
Copyright Texts Johanna Maria Vermeulen, 2023 
29 
2. Ocular Symptoms 
    Oogsymptomen 
 
Please circle the number between 0 and 10 that describes your symptom. 
Omcirkel alstublieft het getal tussen 0 en 10 dat uw symptoom omschrijft. 
 
0 = No symptom (e.g. no itchy eyes).   
      Geen symptoom (bijv. geen jeukende ogen). 
      
10 = Most severe symptom (e.g. most severe itchy eyes).   
        Meest ernstige symptoom (bijv. meest ernstige jeukende ogen). 
 
 
 
 
 
 
 
 
 
        
 

Appendix I: VAS – Score 
Copyright Texts Johanna Maria Vermeulen, 2023 
30 
 
No 
symptom 
Geen 
symptoom 
 
 
 
 
 
 
 
 
 
Most 
severe 
symptom 
Meest 
ernstige 
symptoom 
Itchy eyes 
Jeukende 
ogen 
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
Red eyes 
Rode ogen 
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
Burning 
eyes  
Brandende 
ogen 
 
 
 
0 
 
 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
 
 
6 
 
 
7 
 
 
8 
 
 
9 
 
 
10 
Watery eyes 
Tranende 
ogen 
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
 
 
 
 
 
 
 
 

 Appendix II: Adapted NOSE Scale 
 
Copyright Texts Johanna Maria Vermeulen, 2023 
31 
Adapted NOSE Scale ‘Acupuncture for Nasal Congestion in Allergic Rhinitis’ -   
                                      2022 
                                      ‘Acupunctuur voor Verstopte Neus bij Allergische Rhinitis’ –  
                                          2022’ 
                        
 
Date: 
Datum: 
 
Participant number:  
Deelnemersnummer: 
 
Ø To the participant: Please help us to better understand the impact of nasal 
obstruction on your quality of life by completing the following survey (parts 
A, B and C).  
Thank you!            
Aan de deelnemer: Help ons a.u.b. om de impact van de neusobstructie op uw  
kwaliteit van leven beter te grijpen door de volgende vragenlijst (delen A, B en C) in te 
vullen.  
Dank u wel!  
 
 
 
A.) NOSE Scale. 
 
      NOSE Vragenlijst. 
 
      Over the past one month, how much of a problem were the following  
      conditions for you? 
      In hoeverre waren de volgende situaties de afgelopen maand een probleem  
      voor u? 
     
      Please circle the most correct response. 
      Omcirkel alstublieft het best passende antwoord. 
 
 
Not a 
problem 
Geen 
problem 
Very mild 
problem 
Licht 
probleem 
 
Moderate 
problem 
Matig 
probleem 
 
Fairly bad 
problem 
Redelijk 
ernstig 
probleem 
Severe 
problem 
Ernstig 
probleem 
 
Nasal 
congestion 
or 
stuffiness  
Verstopte 
neus of vol 
gevoel  
 
 
 
 
0 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
Nasal 
blockage or 
obstruction 
 
 
0 
 
 
1 
 
 
2 
 
 
3 
 
 
4 

 Appendix II: Adapted NOSE Scale 
 
Copyright Texts Johanna Maria Vermeulen, 2023 
32 
Neusblokkade 
of obstructie 
 
Trouble 
breathing 
through my 
nose 
Moeite met 
ademen door 
de neus 
 
 
 
 
0 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
Trouble 
sleeping 
Moeite met 
slapen  
 
 
 
 
0 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
Unable to 
get enough 
air through 
my nose 
during 
exercise or 
exertion 
Niet 
voldoende 
lucht door de 
neus krijgen 
bij sport of 
inspanning 
 
 
 
 
 
 
 
0 
 
 
 
 
 
 
1 
 
 
 
 
 
 
2 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
B.) General Addition.  
      Algemene Aanvulling.  
 
      Please circle the most correct response. 
      Omcirkel alstublieft het best passende antwoord. 
 
 
 
 
 
Excellent 
Uitstekend 
 
Very good 
Heel goed 
 
Good 
Goed 
 
Fair 
Redelijk 
 
Poor 
Slecht 
How is your 
general 
health? 
Hoe is uw 
gezondheid in 
het algemeen?  
 
 
 
 
0 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 

 Appendix II: Adapted NOSE Scale 
 
Copyright Texts Johanna Maria Vermeulen, 2023 
33 
How is your 
concentration?  
Hoe is uw 
concentratie? 
 
 
 
0 
 
 
1 
 
 
2 
 
 
3 
 
 
4 
How is your 
energy level? 
Hoe is uw 
energieniveau?  
 
 
 
0 
 
 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
C.) Specific Addition Diving and Flying. 
      Specifieke Aanvulling Duiken en Vliegen. 
 
      Over the past one month, how much of a problem were the following  
      conditions for you? 
      In hoeverre waren de volgende situaties de afgelopen maand een probleem  
      voor u? 
 
      In the case you did not dive or fly, please answer: ‘Not applicable (99)’. 
      In het geval u niet dook of vloog, antwoord a.u.b: ‘Niet van toepassing (99)’. 
 
      Please circle the most correct response. 
      Omcirkel alstublieft het best passende antwoord. 
    
 
 
Not a 
problem 
Geen 
problem 
Very mild 
problem 
Licht 
problem 
Moderate 
problem 
Matig 
Probleem 
Fairly 
bad 
proble
m 
Redelijk 
ernstig 
problee
m 
Severe 
problem 
Ernstig 
probleem 
Not 
applica
ble 
Niet van 
toepassi
ng 
Equalizing 
pressure 
of the 
ears while 
diving 
Klaren van 
de oren 
tijdens 
duiken  
 
 
 
 
 
0 
 
 
 
 
1 
 
 
 
 
2 
 
 
 
 
3 
 
 
 
 
4 
 
 
 
 
99 
Equalizing 
pressure 
of the 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 Appendix II: Adapted NOSE Scale 
 
Copyright Texts Johanna Maria Vermeulen, 2023 
34 
ears while 
flying 
Klaren van 
de oren 
tijdens 
vliegen 
 
 
0 
 
1 
 
2 
 
3 
 
4 
 
99 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
35 
Appendix III: Working Schedule ‘Acupuncture for Nasal Congestion in Allergic   
                       Rhinitis’ – 2023 
 
 
INTAKES 
WEEK 
1 
WEEK 2 
WEEK 3 
WEEK 4 
1-17 May 
Acu 1 
 
Spray 
1 
 
Acu 
2 
Acu 3 
Acu 4 
Acu 5 
Acu 6 
 
22-23 
May 
24 
May 
25-
26 
May 
30-31 
May 
1-2 
June 
8-9  
June 
15-16  
June 
 
WEEK 5 
WEEK 6 
Follow UP 1 
Follow UP 2 
Acu 7 
Final 
spray 
Acu 8 
Spray 
Acu 
Spray 
Acu 
22-23 
June 
28 
June 
29-30 
June 
12 
July 
13-14 
July 
30 
August 
31 
August-  
1 
September 
 
 
INTAKES 
WEEK 
1 
WEEK 2 
WEEK 3 
WEEK 4 
 
Acu 1 
 
Spray 1 
 
Acu 2 
Acu 3 
Acu 4 
Acu 5 
Acu 6 
June-July-
August 
4 
September 
6 
September 
7 
September 
11 
September 
14 
September 
21 
September 
28 
September 
 
WEEK 5 
WEEK 6 
Follow UP 1 
Follow UP 2 
Acu 7 
Final 
spray 
Acu 8 
Spray 
Acu 
Spray 
Acu 
5 October 
11 October 
12 October 
25 October 
26 October 
13 
December 
14 
December 
 
 
INTAKES 
WEEK 
1 
WEEK 2 
WEEK 3 
WEEK 4 
 
Acu 1 
 
Spray 
1 
 
Acu 2 
Acu 3 
Acu 4 
Acu 5 
Acu 6 
January-
February 
2024 
4 
March 
6 
March 
7 
March 
11 
March 
14  
March 
21 
March 
28  
March 
 
WEEK 5 
WEEK 6 
Follow UP 1 
Follow UP 2 
Acu 7 
Final 
spray 
Acu 8 
Spray 
Acu 
Spray 
Acu 
 
 
4 April 
10 April 
11 April 
24 April 
25 April 
12 June 
13 June 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
36 
Appendix IV: Additional Scientific Research regarding Efficacy of Acupuncture  
                       for Complaints of Allergic Rhinitis 
 
Acupuncture may induce anti-inflammatory effects in AR[35] (including antihistamine 
effects (reduction of histamine-induced itch is proven in healthy subjects[36, 37, 38]), and 
downregulation of proinflammatory neuropeptides substance P (SP) and vasoactive 
intestinal peptide (VIP), which is associated with improvements in AR signs and 
symptoms[39]).   
 
There are two small studies (i.e. Heidelberg studies, consisting of one single treatment 
to measure the immediate effect of acupuncture) that are focused on nasal congestion 
(due to hypertrophic inferior turbinates or chronic rhinosinusitis without polyposis in 
2009 with 24 participants[12] and due to hypertrophic inferior turbinate as a result of 
allergic and chronic rhinitis in 2015 with 25 participants[40]).  
The first Heidelberg study (2009) was not performed properly as the control (sham 
acupuncture) group used specific acupuncture points (such as GV-20 (Baihui) which 
can be used for nasal obstruction and nasal discharge) but they were mentioned to be 
non-specific points (control acupuncture showed an improvement in VAS but a 
decrease of nasal air flow (NAF)[12]). Verum acupuncture was significant in improving 
VAS and NAF but less than xylometazoline[12].  
The second Heidelberg study (2015) used points in the control (sham) acupuncture 
group that were not representing existing points but control acupuncture delivered better 
results than expected[40]. Both Heidelberg studies were not focused on nasal congestion 
in exclusively AR and not performed longer to measure long-term effects as well. Both 
studies used sham acupuncture in the control arms, which is no real (not a valid) 
placebo treatment[41, 42](sham acupuncture is considered as an active placebo, also 
called minimal acupuncture[43]). 
One Korean study (2005) examined nasal obstruction in persistent allergic rhinitis after 
one single acupuncture treatment but also used sham acupuncture for the control arm. 
The conclusion was that acupuncture improved nasal obstruction but that further 
research is needed to observe the long-term effect[44]. 
There are acupuncture studies focused on AR in general, which show its effectiveness 
such as AR studies from B. Brinkhaus (2008[45], ACUSAR trial in 2010[46]) but these 
trials did not work with a totally fixed set of acupuncture points for every patient (but with 
an individual treatment per patient according Chinese medicine principles, which is seen 
as less scientific from Western viewpoint). The Brinkhaus trials used sham acupuncture 
in one of the control arms (while referring it is no placebo[46]). The ACUSAR trial showed 
that acupuncture is effective improving the QOL in SAR patients[47]. 
In AR studies from for example Choi (2013)[48] and Xue (2002, 2007)[17, 16] sham 
acupuncture was used as well in (one of) the control group (s) but sham acupuncture is 
no real placebo treatment[42, 43].  
However, none of these mentioned studies were specifically focused on nasal 
congestion in AR and/or using a strictly designed protocol.    
 
 
 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
37 
15. 
REFERENCES 
 
1. 
Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 
2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). 
Allergy. 2008;63(86):8-160. doi:10.1111/j.1398-9995.2007.01620.x 
2. 
Website M. Allergische rhinitis. Updated November 13, 2018. Accessed December 3, 
2021. https://www.mylan.nl/nl-nl/therapeutische-gebieden/allergische-rhinitis 
3. 
Kjaergaard T, Cvancarova M, Steinsvag SK. Nasal congestion index: A measure for nasal 
obstruction. Laryngoscope. 2009;119(8):1628-1632. doi:10.1002/lary.20505 
4. 
Ichimura K. Mechanism of nasal obstruction in patients with allergic rhinitis. Clin Exp 
Allergy. 2010;10(1):20-27. https://doi.org/10.1111/j.1472-9733.2010.01151.x 
5. 
Lieberman P, Kaliner MA, Wheeler WJ. Open-label evaluation of azelastine nasal spray in 
patients with seasonal allergic rhinitis and nonallergic vasomotor rhinitis. Curr Med Res Opin. 
2005;21(4):611-8. doi:10.1185/030079905X41408 
6. 
Craig TJ, Sherkat A, Safaee S. Congestion and sleep impairment in allergic rhinitis. Curr 
Allergy Asthma Rep. 2010;10(2):113-121. doi:10.1007/s11882-010-0091-5 
7. 
Skoner DP. Complications of allergic rhinitis. J Allergy Clin Immunol. 2000;105(6 Pt 
2):S605-9. doi:10.1067/mai.2000.106150 
8. 
Sullivan A, Kushnir N, (Original authors: Scarupa M, Kaliner, MA). World Allergy 
Organization website. In-Depth Review of Allergic Rhinitis. June, 2005. Updated October 2020. 
Accessed January 26, 2021. https://www.worldallergy.org/education-and-
programs/education/allergic-disease-resource-center/professionals/in-depth-review-of-
allergic-rhinitis 
9. 
Bousquet PJ, Demoly P, Devillier P, Mesbah K, Bousquet J. Impact of allergic rhinitis 
symptoms on quality of life in primary care. Int Arch Allergy Immunol. 2013;160(4):393-400. 
doi:10.1159/000342991 
10. 
Law AW, Reed SD, Sundy JS, Schulman KA. Direct costs of allergic rhinitis in the United 
States: estimates from the 1996 Medical Expenditure Panel Survey. J Allergy Clin Immunol. 
2003;111(2):296-300. doi:10.1067/mai.2003.68 
11. 
Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: 
an updated practice parameter. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-84. 
doi:10.1016/j.jaci.2008.06.003 
12. 
Sertel S, Bergmann Z, Ratzlaff K, Baumann I, Greten HJ, Plinkert PK. Acupuncture for 
nasal congestion: A prospective, randomized, double-blind, placebo-controlled clinical pilot 
study. Am J Rhinol Allergy. 2009;23(6):e23–e28. doi:10.2500/ajra.2009.23.3380 
13. 
GM Instruments website. Peak Nasal Inspiratory Flow (PNIF) Meter. Accessed December 
24, 2022. https://gm-instruments.com/products/nasal-measurements/pnif-meter 
14. 
Balsalobre Filho L, Pezato R, Gasparini H, Haddad F, Gregório L, Fujita R. Acute impact of 
continuous positive airway pressure on nasal patency. International forum of allergy & 
rhinology. 2017;7doi:10.1002/alr.21948 
15. 
Balsalobre L, Figueiredo AB, Pezato R, Fujita RR. Effect of topical corticosteroids on nasal 
patency after acute positive airway pressure exposure. Braz J Otorhinolaryngol. 2021;87(3):326-
332. doi:10.1016/j.bjorl.2019.09.011 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
38 
16. 
Xue CC, English R, Zhang JJ, Da Costa C, Li CG. Effect of acupuncture in the treatment of 
seasonal allergic rhinitis: a randomized controlled clinical trial. Am J Chin Med. 2002;30(1):1-11. 
doi:10.1142/S0192415X0200020X 
17. 
Xue CC, An X, Cheung TP, et al. Acupuncture for persistent allergic rhinitis: a 
randomised, sham-controlled trial. Med J Aust. 2007;187(6):337-341. doi:10.5694/j.1326-
5377.2007.tb01275.x 
18. 
Lumry W, Prenner B, Corren J, Wheeler W. Efficacy and safety of azelastine nasal spray 
at a dose of 1 spray per nostril twice daily. Ann Allergy Asthma Immunol. 2007;99(3):267-72. 
doi:10.1016/S1081-1206(10)60663-1 
19. 
Yuan Y, Ren J, Huang L, et al. Chinese English Dictionary of Traditional Chinese Medicine. 
RenMinWeiSheng, 1997. 
20. 
Feng S, Han M, Fan Y, et al. Acupuncture for the treatment of allergic rhinitis: a 
systematic review and meta-analysis. Am J Rhinol Allergy. 2015;29(1):57-62. 
doi:10.2500/ajra.2015.29.4116 
21. 
Yin Z, Geng G, Xu G, Zhao L, Liang F. Acupuncture methods for allergic rhinitis: a 
systematic review and bayesian meta-analysis of randomized controlled trials. Chin Med. 
2020;15:109. doi:10.1186/s13020-020-00389-9 
22. 
Cheng L, Chen J, Fu Q, et al. Chinese Society of Allergy Guidelines for Diagnosis and 
Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res. 2018;10(4):300-353. 
doi:10.4168/aair.2018.10.4.300 
23. 
Zhang YQ. Clinical experience in acupuncture treatment of allergic rhinitis. J Tradit Chin 
Med. 2009;29(3):186-189. doi:10.1016/s0254-6272(09)60062-5 
24. 
Petti FB, Liguori A, Ippoliti F. Study on cytokines IL-2, IL-6, IL-10 in patients of chronic 
allergic rhinitis treated with acupuncture. Tradit Chin Med. 2002;22(2):104-111.  
25. 
Sun PL. Management of Postoperative Pain with Acupuncture. Elsevier Churchill 
Livingstone, 2007. 
26. 
Kaliner MA. Azelastine and olopatadine in the treatment of allergic rhinitis. Ann Allergy 
Asthma Immunol. 2009;103(5):373-80. doi:10.1016/S1081-1206(10)60355-9 
27. 
Berger WE, Fineman SM, Lieberman P, Miles RM. Double-blind trials of azelastine nasal 
spray monotherapy versus combination therapy with loratadine tablets and beclomethasone 
nasal spray in patients with seasonal allergic rhinitis. Rhinitis Study Groups. Ann Allergy Asthma 
Immunol. 1999;82(6):535-41. doi:10.1016/s1081-1206(10)63161-4 
28. 
Horak F. Effectiveness of twice daily azelastine nasal spray in patients with seasonal 
allergic rhinitis. Ther Clin Risk Manag. 2008;4(5):1009-22. doi:10.2147/tcrm.s3229 
29. 
Kaliner MA, Berger WE, Ratner PH, Siegel CJ. The efficacy of intranasal antihistamines in 
the treatment of allergic rhinitis. Ann Allergy Asthma Immunol. 2011;106(2 Suppl):S6-S11. 
doi:10.1016/j.anai.2010.08.010 
30. 
Patel P, D'Andrea C, Sacks HJ. Onset of action of azelastine nasal spray compared with 
mometasone nasal spray and placebo in subjects with seasonal allergic rhinitis evaluated in an 
environmental exposure chamber. Am J Rhinol. 2007;21(4):499-503. 
doi:10.2500/ajr.2007.21.3058 
31. 
Han D, Chen L, Cheng L, et al. A multicenter randomized double-blind 2-week 
comparison study of azelastine nasal spray 0.1% versus levocabastine nasal spray 0.05% in 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
39 
patients with moderate-to-severe allergic rhinitis. ORL J Otorhinolaryngol Relat Spec. 
2011;73(5):260-5. doi:10.1159/000330269 
32. 
Horak F, Zieglmayer UP, Zieglmayer R, et al. Azelastine nasal spray and desloratadine 
tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action 
and efficacy. Curr Med Res Opin. 2006;22(1):151-157. doi:10.1185/030079906X80305 
33. 
Sur DK, Scandale S. Treatment of Allergic Rhinitis. Am Fam Physician; 2010;81(12):1440-
1446. June 15, 2010. Accessed February 28. 2021. 
https://www.aafp.org/afp/2010/0615/p1440.html 
34. 
Greiff L, Andersson M, Svensson C, Persson CG. Topical azelastine has a 12-hour 
duration of action as assessed by histamine challenge-induced exudation of alpha 2-
macroglobulin into human nasal airways. Clin Exp Allergy. 1997;27(4):438-44.  
35. 
McDonald JL, Cripps AW, Smith PK, Smith CA, Xue CC, Golianu B. The anti-inflammatory 
effects of acupuncture and their relevance to allergic rhinitis: a narrative review and proposed 
model. Evid Based Complement Alternat Med. 2013;2013:591796. doi:10.1155/2013/591796 
36. 
Belgrade MJ, Solomon LM, Lichter EA. Effect of acupuncture on experimentally induced 
itch. Acta Derm Venereol. 1984;64(2):129-33.  
37. 
Lundeberg T, Bondesson L, Thomas M. Effect of acupuncture on experimentally induced 
itch. Br J Dermatol. 1987;117(6):771-7. doi:10.1111/j.1365-2133.1987.tb07359.x 
38. 
Pfab F, Hammes M, Backer M, et al. Preventive effect of acupuncture on histamine-
induced itch: a blinded, randomized, placebo-controlled, crossover trial. J Allergy Clin Immunol. 
2005;116(6):1386-8. doi:10.1016/j.jaci.2005.08.055 
39. 
McDonald JL, Cripps AW, Smith PK. Mediators, Receptors, and Signalling Pathways in the 
Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture. Evid Based Complement 
Alternat Med. 2015;2015:975632. doi:10.1155/2015/975632 
40. 
Albrecht. Measurable impact of acupuncture on mucosal swelling of inferior turbinates: 
a prospective, randomized, controlled study. Acta Oto-Laryngologica. 2015;135:169-176. 
doi:10.3109/00016489.2014.973533 
41. 
Lund I, Naslund J, Lundeberg T. Minimal acupuncture is not a valid placebo control in 
randomised controlled trials of acupuncture: a physiologist's perspective. Chin Med. 2009;4:1. 
doi:10.1186/1749-8546-4-1 
42. 
Wang Y-R, Zhao J-P, Hao D-F. Is sham acupuncture a real placebo: Skeptical for sham 
acupuncture. World Journal of Acupuncture - Moxibustion. 2017;27(2):1-5. 
doi:https://doi.org/10.1016/S1003-5257(17)30110-1 
43. 
Briggs JP, Shurtleff D. Acupuncture and the Complex Connections Between the Mind and 
the Body. JAMA. 2017;317(24):2489-2490. doi:10.1001/jama.2017.7214 
44. 
Jo JH, Hong KE, Kang WC, Choi SM, Park JE. Effect of acupuncture on nasal obstruction in 
patients with persistent allergic rhinitis: a randomised, controlled trial. Journal of Korean 
Acupuncture and Moxibustion. 2005;22(6):229-239.  
45. 
Brinkhaus B, Witt CM, Jena S, Liecker B, Wegscheider K, Willich SN. Acupuncture in 
patients with allergic rhinitis: a pragmatic randomized trial. Ann Allergy Asthma Immunol. 
2008;101(5):535-43. doi:10.1016/S1081-1206(10)60294-3 
46. 
Brinkhaus B, Witt CM, Ortiz M, et al. Acupuncture in seasonal allergic rhinitis (ACUSAR)--
design and protocol of a randomised controlled multi-centre trial. Forsch Komplementmed. 
2010;17(2):95-102. doi:10.1159/000303012 

ANCAR Trial 
Copyright Texts Johanna Maria Vermeulen, 2023 
40 
47. 
Reinhold T, Roll S, Willich SN, Ortiz M, Witt CM, Brinkhaus B. Cost-effectiveness for 
acupuncture in seasonal allergic rhinitis: economic results of the ACUSAR trial. Ann Allergy 
Asthma Immunol. 2013;111(1):56-63. doi:10.1016/j.anai.2013.04.008 
48. 
Choi SM, Park JE, Li SS, et al. A multicenter, randomized, controlled trial testing the 
effects of acupuncture on allergic rhinitis. Allergy. 2013;68(3):365-74. doi:10.1111/all.12053