Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: a Multicenter Randomized Controlled Trial
Phase: NA
Conditions: Chronic Prostatitis With Chronic Pelvic Pain Syndrome
Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences

 
 
 
 
Acupuncture for Chronic Prostatitis/Chronic 
Pelvic Pain Syndrome 
 
Study Protocol with Statistical Analysis Plan (SAP) and 
Informed Consent Form (ICF) 
 
NCT number: NCT03213938 
September 4, 2017 

 1 / 34 
 
Table of contents 
1. Study Contact and Organization ........................................................................................................... 3 
1.1 Principal Investigator .................................................................................................................. 3 
1.2 Coordinating Center ................................................................................................................... 3 
1.3 Data Management Center ........................................................................................................... 3 
1.4 Statistical Analysis ...................................................................................................................... 3 
1.5 Recruiting Sites .......................................................................................................................... 3 
2. Introduction .......................................................................................................................................... 6 
3. Study Design and Objective ................................................................................................................. 7 
3.1 Objective .................................................................................................................................... 7 
3.2 Primary Hypothesis .................................................................................................................... 7 
3.3 Study Design and Organizations ................................................................................................. 7 
3.4 Study Time Frame ...................................................................................................................... 7 
3.5 Trial Flow Chart ......................................................................................................................... 8 
4. Study Population .................................................................................................................................. 9 
4.1 Diagnosis criteria ........................................................................................................................ 9 
4.2 Eligibility criteria ........................................................................................................................ 9 
4.3 Exclusion criteria ........................................................................................................................ 9 
5. Subject Recruitment, Screening, Enrolment, and Group Assignment ................................................ 10 
5.1 Recruitment and Informed Consent .......................................................................................... 10 
5.2 Screening and Baseline Assessment ......................................................................................... 10 
5.3 Group Assignment .................................................................................................................... 12 
6. Randomization and Blinding .............................................................................................................. 12 
6.1 Randomization .......................................................................................................................... 12 
6.2 Blinding .................................................................................................................................... 12 
7. Interventions ....................................................................................................................................... 12 
7.1 Acupuncture .............................................................................................................................. 13 
7.2 Sham Acupuncture .................................................................................................................... 13 
7.3 Standardization of Treatment .................................................................................................... 13 
7.4 Permitted and Prohibited Concomitant Treatments .................................................................. 14 
8. Subject Evaluation .............................................................................................................................. 14 
8.1. Outcomes Measurements ......................................................................................................... 14 
8.1.1 Primary Outcomes ......................................................................................................... 14 
8.1.2 Secondary Outcomes ..................................................................................................... 15 
8.2 Evaluation Procedures .............................................................................................................. 16 
8.2.1 Schedule of Evaluation .................................................................................................. 16 
8.2.2 Baseline assessment ....................................................................................................... 17 
8.2.3 Eight-week Treatment Phase ......................................................................................... 17 
8.2.4 Twenty-four-week Follow-up Phase .............................................................................. 17 
9. Safety Assessment and Subject Withdrawal ....................................................................................... 17 
9.1 Adverse Events ......................................................................................................................... 17 
9.2 Subject Withdrawals ................................................................................................................. 17 
10. Administrative Responsibilities ........................................................................................................ 18 
10.1 Institutional Review Board ..................................................................................................... 18 

 2 / 34 
 
10.2 Funding ................................................................................................................................... 18 
10.3 Compliance Improvement ...................................................................................................... 18 
10.4 Data Management ................................................................................................................... 18 
10.4.1 The Raw Data Management and Archiving ................................................................. 18 
10.4.2 Data Entry and Storage ................................................................................................ 18 
10.4.3 Data Verification and Problems Solving ...................................................................... 19 
10.4.4 Medical Coding ........................................................................................................... 19 
10.4.5 Data Report .................................................................................................................. 19 
10.4.6 Data Auditing and Blinding Review ............................................................................ 19 
10.4.7 Database Locking ........................................................................................................ 19 
10.5 Quality Control ....................................................................................................................... 19 
11. Statistical consideration .................................................................................................................... 20 
11.1 Sample Size Calculations........................................................................................................ 20 
11.2 Statistical Analysis .................................................................................................................. 20 
12. References ........................................................................................................................................ 21 
Appendix 1 Patient Informed Consent ................................................................................................... 23 
Appendix 2 Outcome Assessment Tools ................................................................................................ 27 
National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) ............................. 28 
International Prostate Symptom Score (IPSS) ................................................................................ 29 
Hospital Anxiety and Depression Scale (HADS) ........................................................................... 30 
International Index of Erectile Function 5 (IIEF-5) ........................................................................ 31 
European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) ..................................................... 32 
Expectation Assessment ................................................................................................................. 33 
 

 3 / 34 
 
1. Study Contact and Organization 
1.1 Principal Investigator 
Zhishun Liu, MD PhD 
Guang’anmen Hospital, China Academy of Chinese Medical Sciences 
5 Beixian’ge Street, Xicheng District, Beijing, China, 100053 
Phone: +86 10 88002331 
Email: liuzhishun@aliyun.com 
 
1.2 Coordinating Center 
Guang’anmen Hospital, China Academy of Chinese Medical Sciences 
Zhishun Liu, MD PhD 
Guang’anmen Hospital, China Academy of Chinese Medical Sciences 
5 Beixian’ge Street, Xicheng District, Beijing, China, 100053 
Phone: +86 10 88002331 
Email: liuzhishun@aliyun.com 
 
Baoyan Liu, MD 
Guang’anmen Hospital, China Academy of Chinese Medical Sciences 
5 Beixian’ge Street, Xicheng District, Beijing, China, 100053 
Phone: +86 13601180524 
Email: baoyanjournal@163.com 
 
1.3 Data Management Center 
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences 
Liyun He, MD PhD  
16 Dongzhimennei South Alley, Dongcheng District, Beijing, China, 100700  
Phone: +86 13581770875  
Email: hely3699@163.com 
 
1.4 Statistical Analysis 
Data Centre of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences 
Yan Liu, MD 
16 Dongzhimennei South Alley, Dongcheng District, Beijing, China, 100700  
Phone: +86 13811299493  
Email: sasliu@yeah.net 
 
1.5 Recruiting Sites 
Dongfang Hospital Beijing University of Chinese Medicine 
Hui Hu, MD PhD 
Site Principal Investigator, Director of Acupuncture and Moxibustion Department 
6 Fangxingyuan 1 Street, Fengtai District, Beijing, China, 100078 
Phone: +86 10 67689713 
Email: dfzhenjiu@126.com 
 

 4 / 34 
 
Beijing Fengtai Hospital of Integrated Traditional and Western Medicine 
Yulong Ding,MD 
Site Principal Investigator, Director of Acupuncture and Moxibustion Department 
Dongshanposanli Jia 60#, Changxindian Street, Fengtai District, Beijing, China, 100053 
Phone: +86 10 83801526 
Email: princezzbmw@163.com 
 
West China Hospital of Sichuan University 
Ning Li, MD 
Site Principal Investigator, Director of Acupuncture and moxibustion Department 
37 Guoxuexiang, Wuhou District, Chengdu, Sichuan, 610041 
Phone: +86 18980601617 
Email: zhenjiuhuaxi@163.com 
 
The Third Affiliated Hospital of Zhejiang Chinese Medical University 
Jianqiao Fang, MD PhD 
Site Principal Investigator, Director of Acupuncture and Moxibustion Department 
219 Moganshan Road, Xihu District, Hangzhou, China, 310005 
Phone: +86 13606707532 
Email: fangjianqiao7532@163.com 
 
The First Affiliated Hospital of Anhui University of Chinese Medicine 
Jun Yang, MD 
Site Principal Investigator 
117 Meishan Road, Hefei, Anhui, China, 230031 
Phone: +86 055 12838581 
Email: yangjunacup@126.com 
 
Hengyang Hospital Affiliated to Hunan University of Chinese Medicine 
Zenghui Yue, MD 
Site Principal Investigator, Director of Acupuncture and Moxibustion Department 
25 Zhengxiang North Road, Zhengxiang District, Hengyang, Hunan, China, 421001 
Phone: +86 18216000369 
Email: 624755064@qq.com 
 
The First Hospital of Hunan University of Chinese Medicine 
Wei Zhang, MD, PhD 
Site Principal Investigator, Director of Acupuncture and Moxibustion Department 
95 Shaoshan Middle Road, Yuhua District, Changsha, Hunan, China, 410007 
Phone: +86 13548639198 
Email: 507395550@qq.com 
 
Guangdong Provincial Hospital of Traditional Chinese Medicine  
Wenbin Fu, MD, PhD 

 5 / 34 
 
Site Principal Investigator, Director of Acupuncture and Moxibustion Department 
111 Dade Road, Yuexiu District, Guangzhou, Guangdong, China, 510120 
Phone: +86 13808888626 
Email: fuwenbin@139.com 
 
Yantai Hospital of Traditional Chinese Medicine  
Zhiwei Zang, MD  
Site Principal Investigator, Director of Acupuncture and moxibustion Department  
39 Xingfu Road, Zhifu District, Yantai, Shandong, China, 265200  
Phone: +86 15553553797  
Email: 860922902@qq.com 
 
Shaanxi Provincial Hospital of Traditional Chinese Medicine  
Tongsheng Su, MD 
Site Principal Investigator, Director of Acupuncture and Moxibustion Department 
2 Xihua Gate, Lianhu District, Xi’an, Shaanxi, China, 71003 
Phone: +86 15929562568 
Email: chinasuts@126.com 

 6 / 34 
 
2. Introduction 
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to the presence of bothersome 
pelvic pain symptoms without an identifiable cause1. Table 1 illustrates the 4 categories of prostatitis 
per the National Institutes of Health (NIH) classification of prostatitis syndromes. CP/CPPS affects 
approximately 10–16% of men worldwide1-4. Men of all ages can be impacted, among whom those 
aged 36–50 years are the most commonly affected5. There is no apparent racial predisposition to this 
disease.  
Common symptoms of CP/CPPS include discomfort in the perineum, suprapubic region, and lower 
urinary tract symptoms6. Patients with CP/CPPS also frequently experience a wide array of sexual 
dysfunctions, including erectile dysfunction (ED), painful ejaculation and premature ejaculation 
(PE)7-11, on top of symptoms suggestive of negative cognition or emotional consequences12. The 
aforementioned symptoms negatively impact upon the patient’s quality of life (QoL) to a similar degree 
or worse than those of congestive heart failure, Crohn’s disease, diabetes mellitus or angina13, 14. 
Because of its high prevalence and lack of effective therapies, direct and indirect costs associated with 
CP/CPPS are substantial15. Approximately 25% of men experience loss of work and approximately 50% 
have reduced leisure time at some point due to CP/CPPS16. The direct and indirect cost of care in China 
approaches 8059 CNY per person in 200917, and data indicate that in the USA, the total annual cost for 
patients with prostatitis was US$4387 in 200615.  
Unlike acute/chronic bacterial prostatitis, the cause of CP/CPPS is unknown and no well-conducted 
epidemiologic studies are available to support any particular risk factors18. The diagnosis of CP/CPPS 
is mainly based on symptoms. Treatments for CP/CPPS usually include alpha-blockers, antibiotics, 
nonsteroidal anti-inflammatory drugs (NSAIDs), and phytotherapy. Alpha-blockers and antibiotics 
have moderate effects on pain, voiding and QoL19. Both alpha-blockers and antibiotics are 
recommended for patients with CP/CPPS for less than 1 year, but only antibiotics are recommended in 
treatment-naïve patients. NSAIDs and phytotherapy are less commonly use d, because of lack of 
research evidence19. Although advances have been made in research and developing novel treatment 
options, definitive treatments for CP/CPPS are still lacking19. Besides, pharmacological interventions 
are accompanied with adverse effects such as dizziness, nausea, and postural hypotension, which also 
reduce patients’ compliance to treatments20. Previous studies suggest that acupuncture may be a 
potential treatment for CP/CPPS 21-25. However, owing to small sample sizes and other methodological 
limitations of clinical trials, the efficacy of acupuncture in CP/CPPS remains inconclusive 19, 26. In 
addition, the durable efficacy of the acupuncture is still unclear.27  
NIH consensus classification of prostatitis 
Definition 
(I) Acute bacterial prostatitis 
Acute infection of the prostate 
(II) Chronic bacterial prostatitis 
Chronic or recurrent infection of the prostate 
(III) Chronic prostatitis/chronic pelvic pain 
syndrome 
No demonstrated infection 
    A. Inflammatory 
Leukocytes in expressed prostatic secretions, post 
prostate massage urine, or semen 
    B. Noninflammatory 
No evidence of inflammation 
(IV) Asymptomatic inflammatory 
prostatitis 
No subjective symptoms detected, inflammation 
shown either by prostate biopsy or the presence of 
leukocytes in EPS/semen during evaluation for 
infertility or other disorders 

 7 / 34 
 
NIH, National Institutes for Health 
Table 1. NIH consensus classification and definition of 4 categories of prostatitis1 
3. Study Design and Objective 
3.1 Objective 
The objective of this multi-center, randomized, sham acupuncture-controlled trial is to assess the 
effectiveness of acupuncture for relieving symptoms of CP/CPPS.  
3.2 Primary Hypothesis 
The primary study hypothesis is that acupuncture is more effective than sham acupuncture in 
relieving symptoms of CP/CPPS after treatment and 24 weeks after the cessation of treatment. 
3.3 Study Design and Organizations 
This is a multicenter, participants-blinded, parallel-group, randomized controlled study conducted in 
China. 
The participants will be recruited in 10 clinical sites, which are Dongfang Hospital Beijing 
University of Chinese Medicine; Beijing Fengtai Hospital of Integrated Traditional and Western 
Medicine; West China Hospital of Sichuan University; The Third Affiliated Hospital of Zhejiang 
Chinese Medical University; The First Affiliated Hospital of Anhui University of Chinese Medicine; 
Hengyang Hospital Affiliated to Hunan University of Chinese Medicine; The First Hospital of Hunan 
University of Chinese Medicine; Guangdong Provincial Hospital of Traditional Chinese Medicine; 
Yantai Hospital of Traditional Chinese Medicine; and Shaanxi Provincial Hospital of Traditional 
Chinese Medicine. Guang’anmen Hospital, China Academy of Chinese Medical Sciences will be 
responsible for study design and organization. A data coordination center will be established at China 
Academy of Chinese Medical Sciences (CACMS) to monitor data management. 
3.4 Study Time Frame 
The duration of the study for each participant will be 34 weeks: 2 weeks before randomization as 
eligibility screening and baseline assessment, 8 weeks of treatment period, and 24 weeks of follow up 
period after the cessation of treatment (Figure 1. Study Design). 
 
Figure 1. Study Design 
There will be twelve clinical visits:  
Visit 1 will be scheduled during weeks -1 and -2 as eligibility screening and baseline assessment; 
Visit 2 will be scheduled for baseline assessment and randomization;  
Visits 3-10 (20 sessions of treatments) will be scheduled for the 8-week treatment period; 
Visits 11 and 12 will be scheduled at weeks 20 and 32, respectively, during 24-week follow-up 
period. 

 8 / 34 
 
3.5 Trial Flow Chart 
The trial flow chart is shown in Figure 2. 
 
Figure 2. Trial Flow Chart 
EPS, expressed prostatic secretion; PSA, prostate-specific antigen; NIH-CPSI, National Institutes of 
Health Chronic Prostatitis Symptom Index; IPSS, International Prostate Symptom Score; HADS, 
Hospital Anxiety and Depression Scale; IIEF-5, International Index of Erectile Function 5; EQ-5D-5L, 
European Quality of Life-5 Dimensions-5 Levels.

 9 / 34 
 
4. Study Population 
4.1 Diagnosis criteria 
The diagnosis of CP/CPPS is made according to the NIH CP/CPPS consensus1, based on medical 
history, physical examination and a process of exclusion. Urologists are responsible for diagnosis and 
the differential diagnosis of CP/CPPS. 
Participants should have a medical history of persistent discomfort or pain in the pelvic region for at 
least 3 months in the previous 6 months and an absence of other lower urinary tract pathologies.  
Physical examinations will be performed for each participant to detect abnormalities, which include 
an abdominal examination, digital rectal examination, external genital examination and perineal 
examination. Abdominal ultrasound will be conducted to assess the condition of other organ and the 
volume of post-void residual urine. Prostate ultrasound will be conducted to rule out prostatic 
hyperplasia. 
Urinalysis will be performed to rule out urinary tract infections. 
A screening “two-glass test”28 will be performed to collect urine specimens and expressed prostatic 
secretion (EPS) for analysis and culture to rule out possible infection. 
A urinary flow rate will be performed for all patients presenting with CP/CPPS to provide 
information about the function of the lower urinary tract.  
Serum prostate-specific antigen (PSA) testing will be completed to screen for the possibility of 
prostate cancer.  
Cystoscopy will be performed in selected patients (decided by urologists) with hematuria, suspicious 
cytology, irritative and obstructive voiding symptoms. 
4.2 Eligibility criteria 
Men will be included in the study if they meet the following criteria: 
(1) History of pain perceived in the prostate region and absence of other lower urinary tract pathology 
for a minimum of three of the past 6 months. In addition, any associated lower urinary tract 
symptoms, sexual function, and psychological factors should be addressed. Physical examinations, 
urinary analyses, and urine cultures will be performed for all subjects; 
(2)  Age 18 to 50 years; 
(3)  NIH-CPSI total score≥15. 
4.3 Exclusion criteria 
Men will be excluded from the study if they meet one of the following criteria:  
(1) Other types of prostatitis, such as acute bacterial prostatitis, chronic bacterial prostatitis, or 
asymptomatic inflammatory prostatitis; 
(2) Urinary tract infection with a urine culture value >100,000 colony forming units (CFU)/mL, 
clinical evidence of urethritis, including urethral discharge or positive culture, diagnostic of 
sexually transmitted diseases (including gonorrhoea, chlamydia, mycoplasma or trichomonas, but 
not including HIV/AIDS), symptoms of acute or chronic epididymitis; 
(3) Prostate, penile, testicular, bladder, or urethral cancer, seizure disorder in any medical history; 
(4) Inflammatory bowel disease, active urethral stricture, bladder outlet obstruction, neurologic 
disease or disorder affecting the bladder, neurologic impairment or psychiatric disorder preventing 
understanding of consent and self-report scale; 
(5) Overactive bladder, neurogenic bladder, interstitial cystitis, glandular cystitis; 
(6) Organic disease of the urinary system; 
(7) Severe cardiac, lung, cerebrum, liver or renal system disease, or hematopoietic system disease; 

 10 / 34 
 
(8) Residual urine volume≥100 mL; 
(9) Qmax≤15mL/s; 
(10) During previous 4 weeks prior to study participation, used androgen hormone inhibitors 
(finasteride), alpha-blockers (terazosin, doxazosin mesylate. tamsulosin hydrochloride), antibiotics 
(ciprofloxacin hydrochloride), or any other prostatitis-specific medication (including herbal and 
Chinese medicine). 
5. Subject Recruitment, Screening, Enrolment, and Group Assignment 
5.1 Recruitment and Informed Consent 
From October 2017 to December 2019, men with CP/CPPS will be recruited via newspaper, website 
and hospital posters in 10 centers over China. Patients who show interest in the study and meet the 
basic criteria of the study will sign the written informed consent form (see Appendix 1 Patient Inform 
Consent) before the formal screening process. The informed consent form will be reviewed and 
approved by institutional review boards at Guang’anmen Hospital, China Academy of Chinese Medical 
Sciences, and individual clinical site. 
5.2 Screening and Baseline Assessment 
On patients’ official Visit 1 (screening visit) to hospital, they will sign the written informed consent 
form. Research assistants of each site will record their demographic information, course of disease and 
previous treatments. Urologists are responsible for the diagnosis and the differential diagnosis of 
CP/CPPS.  
Patients will receive a series of procedures to screen for eligibility, which will take approximately 
two weeks (weeks -1 to -2). To use the funds rationally and for consideration of the convenience of 
participants, the procedures will be scheduled step by step (Figure 3. Subject Flow Chart), and the 
eligibility criteria will be verified timely during the process. Those fails in one step will not receive 
further screening. During the screening periods, participants will not receive any therapy for CP/CPPS.  
The screening procedures include (in sequence): 
(1) The medical history, demographic information and previous treatments; 
(2) Chinese-version National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI)29, 30; 
(3) Physical examinations (abdominal examination, digital rectal examination, external genital 
examination and perineal examination); 
(4) Urinalysis 
(5) Abdominal ultrasound and prostate ultrasound will be performed; 
(6) Urine and EPS culture; 
(7) Serum PAS testing; 
(8) Urinary flow rate; 
(9) Cystoscopy, if needed. 
Participants who are still eligible after the examinations will complete the baseline outcome 
assessment questionnaires at home, which include International Prostate Symptom Score (IPSS)31, 32, 
the Hospital Anxiety and Depression Scale (HADS)33, International Index of Erectile Function 5 
(IIEF-5)34, European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L)35, and participants’ 
expectation assessment. The NIH-CPSI will completed again. 
To eliminate the possible influence of invasive examinations on baseline assessment as much as 
possible, participants should complete the baseline questionnaires several days after the examinations, 
preferably on the last day of the screening period. During participants’ Visit 2 to hospital, research 
assistants will collect the questionnaires and verify the eligibility.  

 11 / 34 
 
Note: Although the eligibility screening and baseline assessment are interpreted as Visit 1 and Visit 2, 
participants might need to visit the hospital more than twice during the process. The clinical site can 
arrange the procedures of examinations in accordance with the rapidity of each examination in their 
own hospital to save participants’ time and visits to hospital.  
 
Figure 3. Subject Flow Chart 
EPS, expressed prostatic secretion; PSA, prostate-specific antigen; NIH-CPSI, National Institutes of 
Health Chronic Prostatitis Symptom Index; IPSS, International Prostate Symptom Score; HADS, 
Hospital Anxiety and Depression Scale; IIEF-5, International Index of Erectile Function 5; EQ-5D-5L, 
European Quality of Life-5 Dimensions-5 Levels. 

 12 / 34 
 
5.3 Group Assignment 
On patients’ Visit 2 to hospital, eligible participants will be randomly assigned either to acupuncture 
group or sham acupuncture group. The randomization will be completed by Acupuncturists. The details 
of the central randomization will be described below. 
6. Randomization and Blinding 
6.1 Randomization 
In this study, we will use permuted blocks randomization, stratified according to center. A 
web-response system of Central Randomization System for Clinical Research (designed by Clinical 
Evaluation Center, China Academy of Chinese Medical Sciences) will be applied in our trial. The 
allocation sequence will be generated by Institute of Basic Research in Clinical Medicine, China 
Academy of Chinese Medical Sciences using statistical analysis software SAS 9.4 with “proc plan” 
program. After production, the sequence will be signed and sealed by the staff who produce it and kept 
by other staff who take no part in this trial. It will not be allowed to be checked by anyone except the 
top system administrator.  
Only acupuncturists in each center will have access to random numbers and group allocation prior 
to treatment through the web. Participants will be randomly assigned to the acupuncture or sham 
acupuncture group at 1:1 ratio. 
6.2 Blinding 
Research assistants, statisticians, participants, and outcome assessors will be blind to treatment 
allocations. Only acupuncturists are aware of the group allocation to administrate treatments. 
Participants in the sham acupuncture group will receive minimally invasive, superficial needle 
insertion of 2-3mm at non-acupoints. Treatment protocol will be similar to that of the acupuncture 
group, and the acupuncturists will be trained to perform the same needling rituals in both groups.  
To test the success of blinding, within 5 minutes after treatment (sessions 19 or 20) at week 8, 
participants will be told that there are two kinds of acupuncture methods, which are the traditional 
acupuncture where the insertion is relatively deep, and the minimal acupuncture at non-acupoints 
where the insertion is relatively shallow; and participants will be randomly assigned to receive 
traditional acupuncture or minimal acupuncture at non-acupoints at 50% chance respectively. 
Participants will then be asked to answer the question that “Do you think you have received traditional 
acupuncture in the past weeks?” The participants will be able to choose one of the following options as 
the answer: “Yes”, “No” or “Unclear”. 
7. Interventions 
The intervention scheme of this trial will be based on consensus meeting with acupuncturists and 
acupuncture experts from CACMS and result of prior study. Sanyinjiao (SP6), Zhongliao (BL33), 
Shenshu (BL23), and Huiyang (BL35) were selected for the acupuncture treatment group. Based on the 
theories of traditional Chinese medicine (TCM) and acupuncture, the spleen meridian (SP), kidney 
meridian (KI), and liver meridian (LI) intersect at Sanyinjiao (SP6), one of the most frequently used 
acupoints for urological disorders. The urinary bladder meridian (BL) is commonly used for urologic 
disorders, including pelvic pain, lower urinary tract symptoms, and sexual disorders in both male and 
female patients. SP6 locates slightly above the medial malleolus, posterior to the tibia where the tibial 
nerve innervates anatomical structures. Previous research supports the possible beneficial effects of 
sacral nerve stimulation and tibial nerve stimulation on the severity and frequency of chronic pelvic 
pain36. 
There will be two full-time acupuncturists per center responsible for administration of acupuncture 

 13 / 34 
 
and sham acupuncture. In general, acupuncturists will be assigned to the same participants throughout 
the 8-week treatment schedule, except for vacation conflicts and staff turnover. All acupuncturists will 
be registered TCM practitioners with a clinical acupuncture experience of ≥2 years. Disposable 
acupuncture needles (sizes 0.30 × 75, 0.30 × 40 mm and 0.30 × 25 mm, Hwato Brand, Suzhou Medical 
Appliance Factory, Suzhou, China) will be used in this trial. 
Participants in both the acupuncture and the sham acupuncture groups will receive 20 sessions of 
treatment over an 8-week period after baseline (3 sessions in each of the first 4 weeks [ideally every 
other day], and 2 sessions in each of the remaining 4 weeks [ideally every two or three days]). Each 
session will last for 30 minutes.  
7.1 Acupuncture  
Acupoints of bilateral Zhongliao (BL33), Huiyang (BL35), Shenshu (BL23), and Sanyinjiao (SP6), 
which will be located according to the WHO Standardized Acupuncture Points Location37 will be used. 
Zhongliao (BL33) is located in the sacral region, the third posterior sacral foramen. Huiyang (BL35) is 
located in the buttock region, 0.5 proportional bone (skeletal) cun (B-cun) lateral to the extremity of the 
coccyx. Shenshu (BL23) is located in the lumbar region, at the same level as the inferior border of the 
spinous process of the second lumbar vertebra (L2), 1.5 B-cun lateral to the posterior median line. 
Sanyinjiao (SP6) is located on the tibial aspect of the leg, posterior to the medial border of the tibia, 3 
B-cun superiors to the prominence of the medial malleolus. 
With patients in a prone position in relaxation, acupuncturists will use 75% alcohol pads to sterilize 
the skin around the acupuncture points and then insert Hwato-brand disposable acupuncture needles 
(sizes 0.30 × 75 and 0.30 × 40 mm) into the acupuncture points. For bilateral Zhongliao (BL33), the 
needle will be inserted approximately 50–60 mm with a 30°-45° angle in an inferomedial direction. For 
Huiyang (BL35), the needle will be inserted approximately 50–60 mm in a slightly superolateral 
direction. For Shenshu (BL23) and Sanyinjiao (SP6), the needles will be inserted vertically with a 
depth of 25–30 mm. For acupuncture at BL23, BL35 and SP6, needle insertion will be followed by 
acupuncture manipulation of lifting and thrusting combined with twirling and rotating to reach deqi, 
which is defined as the sensation of aches, soreness, swelling, heaviness or numbness in the needle 
location region38. Manipulations will be performed once every 10 minutes, 30 seconds each time. 
Immediately after needle removal, the acupuncturist will gently press the needled skin area with dry 
sterilized cotton balls to avoid bleeding. 
7.2 Sham Acupuncture 
The participants in the sham acupuncture group will receive minimally invasive, superficial needle 
insertion of 2-3mm at bilateral sham BL23, BL33, BL35 and SP6 (non-acupuncture points lateral to the 
corresponding acupoints, 15 mm to BL23, BL33 and BL35; 10 mm to SP6). Treatment protocol will be 
similar to that of the acupuncture group, but Hwato-brand disposable acupuncture needles (size 0.30 × 
25 mm) will be inserted at sham acupoints with depths of 2–3 mm without manipulation39. 
7.3 Standardization of Treatment  
Guang’anmen Hospital will supply single-use, sterile, and disposable acupuncture needles for each 
participating site.  
Two certified acupuncturists will be needed in each site to perform all the treatments, while the 20 
sessions of treatment for each participant should be completed by one specific acupuncturist. All 
acupuncturists in this trial are required to have completed their professional training in acupuncture in 
universities of Chinese medicine with more than 2 years clinical experience.  
To improve the consistency of treatments, acupuncturists at each site will receive trial-specific 

 14 / 34 
 
(standardized operation procedure) training at the project launching session. The training will include 
detailed acupuncture points locations and manipulation methods in both the acupuncture and sham 
acupuncture groups. A video showing detailed information on how to perform the acupuncture and 
sham acupuncture will also be provided.  
To avoid the inadvertent unblinding, acupuncturists will not tell anyone else the treatment allocation. 
The contacts between acupuncturists and participants should be as short as possible.  
The acupuncturists will be instructed to follow standardized operating procedure: 
Step 1:  
The participant is piloted by research assistant to hospital bed, which was screened-off separately 
one-by-one. Their companions will be guided to wait outside the clinic, if any. The specific 
acupuncturist accepts the patient and asks the participant to take a rest. After a short while, 
acupuncturist instructs the patient to lie prone on the bed, with lumbosacral and lower shin areas 
exposed, and tell the participant that a 30-minute treatment will be given.  
Before the first session of treatment, participants will be told that they may receive either the 
traditional acupuncture or sham acupuncture group, and they may not have sensation during the 
30-minute retention of acupuncture needles out of body adaptation.  
Step 2: 
After sterilization, the acupuncturist will start to conduct administration according to treatment 
protocol. The acupuncture group will receive deep insertion of needles at acupuncture points, while the 
sham acupuncture group will receive superficial insertion of needles at non-acupuncture points.  
Step 3:  
After insertion of needles at appropriate areas, acupuncturist will conduct the first needle 
manipulation in the acupuncture group for 30 seconds, while in the sham acupuncture group, 
acupuncturists will hold the handles of acupuncture needles gently for 30 seconds without 
manipulations.  
Step 4:  
After 10 minutes, acupuncturist will conduct the second needle manipulation in the acupuncture 
group for 30 seconds, while in the sham acupuncture group, acupuncturists will hold the handles of 
acupuncture needles gently for 30 seconds without manipulations.   
Step 5: 
After another 10 minutes, acupuncturist will conduct the third needle manipulation in the 
acupuncture group for 30 seconds, while in the sham acupuncture group, acupuncturists will hold the 
handles of acupuncture needles gently for 30 seconds without manipulations.   
Step 6: 
After another 10 minutes, acupuncturist will remove the needles.  
7.4 Permitted and Prohibited Concomitant Treatments 
The use of medications or other therapies specific for symptoms of CP/CPPS will be discouraged 
during this trial, such as α blocker. However, medication use is allowed for intolerable symptoms as 
long as it is recorded accordingly, including the name and the dosage of the medication use. We will 
compare the proportion of subjects using rescue medications between groups. 
8. Subject Evaluation  
8.1. Outcomes Measurements 
8.1.1 Primary Outcomes 
The two co-primary outcomes include the proportions of responders at week 8 and week 32. The 

 15 / 34 
 
responder is defined as a participant with a decline of 6 points or more from baseline in the total score 
of the Chinese version NIH-CPSI. As a validated, self-reported questionnaire, NIH-CPSI is widely 
used to assess CP/CPPS symptoms29, 30. NIH-CPSI consists of 9 items divided into 3 discrete domains: 
pain (0–21 points), urinary symptoms (0–10 points) and QoL (0–12 points), with a total score of 0–43 
points (a higher score indicates worse symptoms). A decline of at least 6 points in NIH-CPSI has been 
identified as the minimal clinically important difference (MCID)25.  
8.1.2 Secondary Outcomes 
Secondary outcomes include: 
(1) Proportion of responders during weeks 1-7, and at week 20.  
The NIH-CPSI will be assessed once a week during treatment, and at week 20 and week 32. The 
responder is defined as who has a decline of 6 or more than 6-point from baseline measured by using 
the NIH-CPSI. 
(2) The change from baseline in NIH-CPSI total score during weeks 1-8, at week 20, and at week 32. 
(3) The change from baseline in NIH-CPSI subscales (pain, urinary symptoms and QoL) during weeks 
1-8, at week 20, and at week 32. 
(4) The change from baseline in IPSS at week 4, week 8, week 20, and week 32. 
IPSS is a valid, reliable and sensitive measure for patients with lower urinary tract symptoms (LUTS); 
it is widely used in clinical practice and research to determine the severity of LUTS, including 
incomplete bladder emptying, frequency of urination, intermittency, urgency, weak urine stream, 
straining and nocturia31, 32. Each of the questions is rated from 0 (not at all) to 5 (almost always); 
severity of LUTS can be graded as mild (0–7), moderate (8–19) or severe (20–35). IPSS will be 
assessed at the end of the 4th, 8th, 20th, and 32nd week. 
(5) The change from baseline in HADS at week 8, week 20, and week 32. 
HADS will be assessed at the end of the week 8, week 20, and week 32. HADS is made up of 7 items 
for the assessment of depression and anxiety; the completion of this scale usually requires 2–5 
minutes33. 
(6) The change from baseline in IIEF-5 at week 8, week 20, and week 32. 
Chinese version IIEF-5 will be assessed at the end of the week 8, week 20, and week 32. The IIEF-5 
consists of 15 items in 5 domains with a total score ranging from 5 to 25 (mild ED, 12–21; moderate 
ED, 8–11; severe ED, 5–7); it is a psychometrically valid and reliable instrument with high 
sensitivity and specificity for detecting treatment effects in patients with ED of a broad  
spectrum of aetiology34. 
(7) The change from baseline in EQ-5D-5L at week 8, week 20, and week 32. 
The EQ-5D-5L will be assessed at the end of week 8, week 20, and week 32. The EQ-5D-5L is a 
generic instrument designed for self-completion and postal surveys; it is well-established and suitable 
for evaluation of QoL in participants with CP/CPPS35. 
(8) The proportions of participants in each response category of the Global Response Assessment 
(GRA) at week 4, week 8, week 20, and week 32. 
The proportions of participants in each response category of the GRA in the two groups after treatment 
will be measured at the end of the week 4, week 8, week 20, and week 32. GRA consists of 7 response 
categories: markedly worsened, moderately worsened, slightly worsened, no change, slightly improved, 
moderately improved, and markedly improved. We will identify a participant who reports “moderate” 
or “marked improvement” as a responder40.  
(9) The change for peak and average urinary flow rate from baseline at weeks 8 and 32. 

 16 / 34 
 
Peak and average urinary flow rates will be measured at weeks 8 and 32. 
(10)  Expectation assessment at baseline 
Expectation assessment will be assessed at baseline, which includes two brief questions to investigate 
whether patients are confident that acupuncture treatment will help their CP/CPPS: “In general, is 
acupuncture effective for controlling the illness?”, “Do you think acupuncture will be helpful to 
improve your CP/CPPS symptoms?” For each question, participants could choose “Yes”, “No” or 
“Unclear” as the answer. 
8.2 Evaluation Procedures 
8.2.1 Schedule of Evaluation 
Table 2. Enrolment, Intervention and Evaluation Schedules 
Abbreviations: NIH-CPSI National Institutes of Health Chronic Prostatitis Symptom Index, IIEF-5 
International Index of Erectile Function 5, HADS Hospital Anxiety and Depression Scale, GRA Global 
Response Assessment, EQ-5D-5L Five-level EuroQol five-dimensional questionnaire, VAS visual 
analogue scale 
 
STUDY PERIOD 
 
Enrolment 
Allocation 
Treatment 
Follow-up 
TIMEPOINT (W, week) 
-2 and -1 
0 
1 
2 
3 
4 
5 
6 
7 
8 
20 
32 
Enrolment 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
× 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
× 
 
 
 
 
 
 
 
 
 
 
 
Demography characteristics 
× 
 
 
 
 
 
 
 
 
 
 
 
Allocation 
 
× 
 
 
 
 
 
 
 
 
 
 
Interventions 
 
 
 
 
 
 
 
 
 
 
 
 
Acupuncture 
 
 
× 
× 
× 
× 
× 
× 
× 
× 
 
 
Sham acupuncture 
 
 
× 
× 
× 
× 
× 
× 
× 
× 
 
 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
Proportion of responders 
 
 
 
 
 
 
 
 
 
× 
 
× 
NIH-CPSI 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
IPSS 
× 
 
 
 
 
× 
 
 
 
× 
× 
× 
IIEF-5 
× 
 
 
 
 
 
 
 
 
× 
× 
× 
HADS 
× 
 
 
 
 
 
 
 
 
× 
× 
× 
EQ-5D-5L 
× 
 
 
 
 
 
 
 
 
× 
× 
× 
GRA 
 
 
 
 
 
× 
 
 
 
× 
× 
× 
Expectation assessment 
× 
 
 
 
 
 
 
 
 
 
 
 
Urinary flow rate 
× 
 
 
 
 
 
 
 
 
× 
 
× 

 17 / 34 
 
8.2.2 Baseline assessment 
The baseline demographic information and outcome assessment will be collected in Visit 1 and Visit 
2, which has been described in 5.2 Screening and Baseline Assessment.  
8.2.3 Eight-week Treatment Phase 
During the 8-week treatment (weeks 1-8), Visits 3-10 are scheduled weekly. 
Participants will complete the NIH-CPSI every week; IPSS and GRA at weeks 4 and 8; and IIEF-5, 
HADS and EQ-5D-5L at week 8. We will provide a self-assessment questionnaires/scales notebook for 
each participant. They will be asked to complete the notebook at home weekly, and bring the manual to 
hospital the following week. Data from the notebook will be checked by outcome assessors, and then 
entered into the electronic database by CRC. Both the outcome assessors and CRC are unaware of the 
group allocation. The data from the notebook will be the raw data for analysis. 
The urinary flow rate will be collected at week 8 after the treatment at hospital.  
Within 5 minutes after treatment (sessions 19 or 20) at the week 8, the success of blinding will be 
assessed by outcome assessors at hospital.  
8.2.4 Twenty-four-week Follow-up Phase 
During the 24-week follow-up (weeks 9-32), Visit 11 will be scheduled at week 20, and Visit 32 will 
be scheduled at week 32. 
Participants will complete the NIH-CPSI, IPSS, GRA, IIEF-5, HADS and EQ-5D-5L at weeks 20 
and 32. Urinary flow rate will be completed at week 32. 
For the results of Visit 11 (week 20), the notebook could be mailed to hospitals or submit to hospitals 
by participants in person. At weeks 32, participants need to visit the hospital in person for the 
examination of urinary flow rate, therefore they will bring the notebook to hospital by themselves. 
9. Safety Assessment and Subject Withdrawal 
9.1 Adverse Events 
We will handle and document the adverse events using the standard operating procedures for 
monitoring and reporting all adverse events.  
According to their potential association with the treatment, AEs will be categorized as 
treatment-related or non-treatment-related within 24 hours after their occurrence. Treatment-related 
adverse events include pain, haematoma, localized infection, broken needle, fainting, nausea, headache, 
dizziness, insomnia, vomiting, or palpitations during or after treatment.  
Serious adverse events will be defined as events requiring hospitalization, causing disability or 
impaired ability to work, threatening life or resulting in death. Any serious adverse events will be 
immediately reported to the principal investigator (ZL) and Medical Ethics Committee at individual 
clinical site and Guang’anmen Hospital within 24 hours. A research assistant will be required to record 
serious adverse events, including information on the time of occurrence, severity, duration, 
measurement, management, and its outcome.  
All the serious adverse events and adverse events will be recorded and measured by participants 
themselves, acupuncturists and urologists through the whole trial. Guang’anmen Hospital has 
insurance covering for harm associated with the interventions during this trial. 
9.2 Subject Withdrawals 
Participants may withdraw from the trial at any time at their own discretion; the investigator may 
also determine whether it is in the best interest of subjects to withdraw from the trial due to worsening 
of symptoms, or the occurrence of a serious adverse event. 

 18 / 34 
 
10. Administrative Responsibilities 
10.1 Institutional Review Board 
For every study site, only when the trial protocol is approved by the institutional review board, the 
enrollment of participant will begin, but all should be after July 25, 2017.  
10.2 Funding 
This study was supported and funded by the “the first batch of key research program in the 13th 
Five-year’’ (ZZ10-012) by the China Academy of Chinese Medical Sciences. The funder will not 
interfere the data collection, analysis, and interpretation; nor in the finishing of the manuscript, and 
decision to submit the manuscript for publication. 
10.3 Compliance Improvement  
(1) Participants should participate in the trial voluntarily, and sign the informed consent;  
(2) Researchers assistants should record the participants’ contact information in detail for the 
convenience of follow-up;  
(3) Before randomization, researchers should inform the participants that all the cost related to the 
examination and treatment would be exempted; 
(4) Each participant’s participation in the trial should be taken charge of by the same research 
assistant and outcome assessor throughout the trial. They will explain the contents of notebook to 
participants if necessary, remind the participants of their schedule by phone or we-chat, and instruct 
participants to complete the notebook.  
(5) For participants who have less compliance, we will still follow them up to record outcome 
measurements through phone or message; 
10.4 Data Management 
10.4.1 The Raw Data Management and Archiving 
We will use Remote Data Capture (RDC) system to perform data entry. The research assistants will 
fill out all the electrical CRF through RDC system. Researchers will inspect the eCRF, and signed 
electrically for the eCRF going into effect. The eCRF and the trace of eCRF revising will be left in the 
Oracle database. 
10.4.2 Data Entry and Storage 
10.4.2.1 Database Building and Testing, Data Entry Interface 
The eCRF will be noted through CDISC SDTM standard, and the data entry interface will be 
generated through the Oracle Clinical software. The data entry interface should be in accordance with 
the paper version CRF as close as possible. The inputted data will be stored in the Oracle database. 
After preliminarily setting up the database, the entry clerks will input some analog data according to 
the CRF to test the database. The testing contains: (1) the agreement of the data entry interface and the 
paper version CRF; (2) the agreement of the exported data from the database and the analog data; (3) 
the agreement of the structure of the exported database and the paper-version CRF. After the testing, 
data administrators should revise the database and make a testing report. Then they electrically signed 
on the approval page of the database to indicate that the testing is completed. The electrical files of the 
analog CRF, Noted CRF, screenshot of the data entry interface, database testing report, and the 
approval page of the database should be saved. If the database updates during the trial, the electrical 
files mentioned above will also need to be updated. 
10.4.2.2 Data Entry and Inspection 
The research assistants take charge of the data entry for our trial. Before the entry, all the research 
assistants will accept the related training according to the data entry handbook. Researchers will inspect 

 19 / 34 
 
the database, and then sign electronically to let the data go in to effect. 
10.4.3 Data Verification and Problems Solving 
Researchers will verify the data through Data Verification Plan (DVP) approved by the data 
administrator and the statisticians. Data queries will be inputted to a data query database, and form the 
DCF. After being inspected, the DCF will then be handed back to the original site, and the researchers 
of the site should answer the queries. Any revision of the database will be recorded through the RDC 
software. 
10.4.4 Medical Coding 
A data administrator who has the medical background will take charge of the medical coding. The 
contents of the coding are the clinical history, adverse events, and combined medication use if any. The 
clinical history and adverse events will be coded through MedDRA dictionary (Version 13.0), and the 
combined medication use will be coded via WHO DD dictionary (Version 2007.03). The lead 
researchers will verify the coded e-files. 
10.4.5 Data Report 
Data report contains the aspects as followed: (1) members of the project; (2) disagreement from the 
primary data management plan; (3) actual finish time of every project; (4) problems and solutions 
during data management (if have any); (5) reconstruction of the database (if have any); (6) distribution 
of the participants; (7) participants who disobey the trial protocol; (8) classifying plan of the statistical 
analysis population. Data report will be performed monthly since the first entry of the eCRF. 
10.4.6 Data Auditing and Blinding Review 
When the data checking is finished, a data auditing and blinding review meeting will be hold. In the 
meeting, the data administrators, statisticians, researchers, clinical inspectors, and other related 
members will have a discussion on the following items according to the data management report and 
the data lists:  
•Distribution of the participants; 
•Protocol disobeying or not; 
•Possible outlier; 
•Baseline data; 
•Outcomes; 
•Statistical analysis plan. 
Participants will be classified to their suitable statistical analysis sets according to the definition in 
the protocol. No patient can be excluded from the analysis, unless getting the permission of the meeting 
participants. All the meeting participants will sign the data locking consent, and the data auditing 
resolution. 
10.4.7 Database Locking 
The database will be locked if it fulfills all the aspects as followed: All the queries have been solved, 
and the database has been updated; No query has been found through the data inspection; The medical 
coding has been completed; The plan of the participants’ classification has been approved; The final 
draft of the SAP has been made, and approved by the project leader. 
The statisticians and the data administrators will sign the data locking form, and then the database will 
be locked. The locked database will be sent to the statisticians for further statistical analysis through the 
data format of SAS. 
10.5 Quality Control 
(1) To guarantee the quality of the study, the trial protocol will be reviewed and may be revised by 

 20 / 34 
 
expert acupuncturists, urologist, and statisticians several times.  
(2) A central randomization system will be adopted to avoid selection bias.  
(3) Strict eligible criteria will be pre-set to restrict the research population. The diagnosis, inclusion and 
exclusion criteria are designed in accordance with the guidance of NIH Chronic Prostatitis Clinical 
Research Network; 
(4) Trial-specific (standardized operation procedure) extensive training will be given to all the research 
staff participating the trial at the project launching session. Acupuncturists will be trained on how to 
use the central randomization system, the standardized manipulation method and needling rituals. 
Outcome assessors will be trained how to fill the case report form. Clinical Research Assistants (CRC) 
will be trained to use data entry system. 
(5) We will provide a self-assessment questionnaires/scales notebook for each participant. Participants 
will be asked to complete the notebook at home. During 8-week treatment period and the last 
assessment (Visit 12), participants will bring the notebook to hospital themselves. For the outcome 
assessment at week 20, they can mail the notebook to hospital or bring the manual to hospital 
themselves. The data from the notebook will be the raw data for analysis, and will be checked and 
recorded in CRF by outcome assessors. The data in CRF will be entered into the electronic database by 
CRC in a double-entry method. The statistical analysis of the data will be calculated by independent 
statisticians. The participants, outcome assessors, CRC and statisticians will all be unaware of the 
group allocation. 
(6) Participation processes in the trial of the same participants should be taken charge of by the same 
acupuncturist, research assistant and outcome assessor throughout the trial.  
(7) A 3-level monitoring system will be established to periodically assess the performance of the trial: 
Level 1, Inspection; Level 2, Supervision; Level 3, Audit. Inspection: The investigator of each center 
will designate at least one researcher who take no part in the intervention to conduct a quality review of 
the center; Supervision: for each center, the study organizer (Guang’anmen Hospital, China Academy 
of Chinese Medical Sciences) will designate at least three researchers who take no part in the 
intervention to monitor the quality of the studies of that center; Audit: the China Academy of Chinese 
Medical Sciences will designate at least five quality control personnel to conduct a quality audit of the 
research. 
11. Statistical consideration 
11.1 Sample Size Calculations 
Sample-size calculations were based on 90% power to detect a difference of 17% between response 
rates in the two groups (63.7% in the acupuncture group compared with 46.7% in the control group) for 
the primary outcome, defined as a decline of 6 or more points in the NIH-CPSI total score21. These 
values are equivalent to an odds ratio of 2.0. On the basis of a two-sided alpha level of 0.05, we 
calculated that a sample of 440 participants will be required (220 in each group). This proposed sample 
size includes a 15% increase to account for dropouts. To control for type I error, the two time points in 
the primary outcomes will have to be positive in order for the trial to prove the efficacy of acupuncture. 
11.2 Statistical Analysis 
Details of the pre-specified statistical analyses can be found in the Statistical Analysis Plan (SAP). 
Prior to database lock and before code breaking, a final version of the SAP shall be issued and 
approved by the study statistician, and the principal investigator. The SAP will define all “pre-specified, 
planned analyses” and provide the general specifications for the analysis of the data to be collected and 
presented in the Clinical Study Report.

 21 / 34 
 
12. References 
1. 
Krieger JN, Nyberg L, Nickel JC. NIH consensus definition and classification of prostatitis. Jama-Journal of the 
American Medical Association 1999;282:236-237. 
2. 
Nickel JC, Downey J, Hunter D, et al. Prevalence of prostatitis-like symptoms in a population based study using the 
National Institutes of Health chronic prostatitis symptom index. Journal of Urology 2001;165:842-845. 
3. 
Collins MM, Meigs JB, Barry MJ, et al. Prevalence and correlates of prostatitis in the health professionals follow-up 
study cohort. J Urol 2002;167:1363-6. 
4. 
Roberts RO, Jacobson DJ, Girman CJ, et al. Prevalence of prostatitis-like symptoms in a community based cohort of 
older men. J Urol 2002;168:2467-71. 
5. 
Litwin MS, McNaughton-Collins M, Fowler FJ, et al. The National Institutes of Health Chronic Prostatitis Symptom 
Index: Development and Validation of a New Outcome Measure. Journal of Urology 1999;162:369-375. 
6. 
Rees J, Abrahams M, Doble A, et al. Diagnosis and treatment of chronic bacterial prostatitis and chronic 
prostatitis/chronic pelvic pain syndrome: a consensus guideline. Bju International 2015;116:509-525. 
7. 
Bartoletti R, Cai T, Mondaini N, et al. Prevalence, incidence estimation, risk factors and characterization of chronic 
prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy: results of a multicenter 
case-control observational study. J Urol 2007;178:2411-5; discussion 2415. 
8. 
Lee SW, Liong ML, Yuen KH, et al. Adverse impact of sexual dysfunction in chronic prostatitis/chronic pelvic pain 
syndrome. Urology 2008;71:79-84. 
9. 
Hao ZY, Li HJ, Wang ZP, et al. The prevalence of erectile dysfunction and its relation to chronic prostatitis in Chinese 
men. J Androl 2011;32:496-501. 
10. 
Chung SD, Keller JJ, Lin HC. A case-control study on the association between chronic prostatitis/chronic pelvic pain 
syndrome and erectile dysfunction. BJU Int 2012;110:726-30. 
11. 
Tran CN, Shoskes DA. Sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome. World J Urol 
2013;31:741-6. 
12. 
Tripp DA, Nickel JC, Wang Y, et al. Catastrophizing and pain-contingent rest predict patient adjustment in men with 
chronic prostatitis/chronic pelvic pain syndrome. J Pain 2006;7:697-708. 
13. 
Collins MM, Pontari MA, O'Leary MP, et al. Quality of life is impaired in men with chronic prostatitis. The chronic 
prostatitis collaborative research network. Journal of Urology 2002;168:395-396. 
14. 
Wenninger K, Heiman JR, Rothman I, et al. Sickness impact of chronic nonbacterial prostatitis and its correlates. J 
Urol 1996;155:965-8. 
15. 
JQ C. Male chronic pelvic pain syndrome: Prevalence, risk factors, treatment patterns, and socioeconomic impact. 
Curr Prostate Rep 2008;6. 
16. 
Calhoun EA, McNaughton Collins M, Pontari MA, et al. The economic impact of chronic prostatitis. Arch Intern Med 
2004;164:1231-6. 
17. 
Liang CZ, Li HJ, Wang ZP, et al. Treatment of chronic prostatitis in Chinese men. Asian J Androl 2009;11:153-6. 
18. 
McNaughton Collins M, MacDonald R, Wilt TJ. Diagnosis and treatment of chronic abacterial prostatitis: a 
systematic review. Ann Intern Med 2000;133:367-81. 
19. 
Engeler DS BA, Dinis-Oliveira P, Elneil S, Hughes J, Messelink EJ, et al. The 2013 EAU guidelines on chronic pelvic 
pain: is management of chronic pelvic pain a habit, a philosophy, or a science? 10 years of development. European 
Urology 2013;64:431-9. 
20. 
McNaughton C, Mac Donald R, Wilt T. Interventions for chronic abacterial prostatitis. Cochrane Database Syst Rev 
2001:CD002080. 
21. 
Lee SWH, Liong ML, Yuen KH, et al. Acupuncture versus sham acupuncture for chronic prostatitis/chronic pelvic 
pain. American Journal of Medicine 2008;121. 

 22 / 34 
 
22. 
Lee S-H, Lee B-C. Electroacupuncture Relieves Pain in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: 
Three-arm Randomized Trial. Urology 2009;73:1036-1041. 
23. 
Qin Z, Wu J, Tian J, et al. Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on 
Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Sci Rep 2016;6:35737. 
24. 
Qin Z, Wu J, Zhou J, et al. Systematic Review of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome. 
Medicine (Baltimore) 2016;95:e3095. 
25. 
Propert KJ, Litwin MS, Wang Y, et al. Responsiveness of the National Institutes of Health Chronic Prostatitis 
Symptom Index (NIH-CPSI). Qual Life Res 2006;15:299-305. 
26. 
Khan A. Updates on therapies for chronic prostatitis/chronic pelvic pain syndrome. World Journal of Pharmacology 
2015;4. 
27. 
Chang SC, Hsu CH, Hsu CK, et al. 9. The efficacy of acupuncture in managing patients with chronic 
prostatitis/chronic pelvic pain syndrome: A systemic review and meta-analysis. Neurourol Urodyn 2017;36:474-481. 
28. 
Nickel JC, Shoskes D, Wang Y, et al. How does the pre-massage and post-massage 2-glass test compare to the 
Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome? J Urol 2006;176:119-24. 
29. 
Hong K, Xu QQ, Jiang H, et al. [Chronic prostatitis symptom index of Chinese]. Zhonghua Nan Ke Xue 
2002;8:38-41. 
30. 
Litwin MS. A review of the development and validation of the National Institutes of Health Chronic Prostatitis 
Symptom Index. Urology 2002;60:14-18. 
31. 
Choi EP, Lam CL, Chin WY. Validation of the International Prostate Symptom Score in Chinese males and females 
with lower urinary tract symptoms. Health Qual Life Outcomes 2014;12:1. 
32. 
Szeto PS. Applilcation of the Chinese version of the international prostate symptom score for the management of 
lower urinary tract symptoms in a primary health care setting. Hong Kong Medical Journal 2008;14:458-464. 
33. 
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361-70. 
34. 
Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an abridged, 5-item version of the 
International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 
1999;11:319-26. 
35. 
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D 
(EQ-5D-5L). Qual Life Res 2011;20:1727-36. 
36. 
Siegel S, Paszkiewicz E, Kirkpatrick C, et al. Sacral nerve stimulation in patients with chronic intractable pelvic pain. 
Journal of Urology 2001;166:1742-1745. 
37. 
Pacific WROftW. WHO Standard Acupuncture Point Locations in the Western Pacific Region. Manila, 
Philippines2008. 
38. 
Zhou K, Fang J, Wang X, et al. Characterization of de qi with electroacupuncture at acupoints with different 
properties. J Altern Complement Med 2011;17:1007-13. 
39. 
Lee SW, Liong ML, Yuen KH, et al. Validation of a sham acupuncture procedure in a randomised, controlled clinical 
trial of chronic pelvic pain treatment. Acupunct Med 2011;29:40-6. 
40. 
Nickel JC, Krieger JN, McNaughton-Collins M, et al. Alfuzosin and symptoms of chronic prostatitis-chronic pelvic 
pain syndrome. New England Journal of Medicine 2008;359:2663-2673. 

 23 / 34 
 
Appendix 1 Patient Informed Consent 
Dear male participants: 
If your doctor thinks you have chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), we 
invite you to participate in this study aiming to evaluate the effectiveness and safety of acupuncture for 
management of CP/CPPS. This study is supported and funded by China Academy of Chinese Medical 
Sciences (ZZ10-012). 
Before you decide to participate in the study, please read the following information carefully. It is 
helpful for you to know this study, understand why the study is performed, the study procedures, the 
duration and benefits of the study, risks and potential discomforts during and after study participation. 
If you like, you can also discuss this study with your relatives and friends, or consult doctors for 
explanation and help to make the decision. 
Introduction 
I. The prevalence of CP/CPPS is high, and it affects approximately 10–16% of men worldwide. The 
diagnosis of CP/CPPS is mainly based on symptoms. Definitive treatments for CP/CPPS are still 
lacking, and pharmacological interventions are accompanied with adverse effects. Previous studies 
suggest that acupuncture may be a potential treatment for CP/CPPS. 
In this study, a randomized controlled trial design will be used and we aim to evaluate the effectiveness 
and safety of acupuncture for relieving symptoms of CP/CPPS. This study will be carried out 
simultaneously in 10 hospitals all over China, and we expect a total number of 440 participants for 
voluntary participation. 
II. Exclusion criteria 
(1) Prostate, bladder, or urethral cancer, seizure disorder in any medical history; 
(2) Inflammatory bowel disease, active urethral stricture, neurologic disease or disorder affecting the 
bladder, liver disease, neurologic impairment or psychiatric disorder preventing understanding of 
consent and self-report scale; 
(3) Urinary tract infection with a urine culture value >100,000 colony forming units (CFU)/mL, 
clinical evidence of urethritis, including urethral discharge or positive culture, diagnostic of sexually 
transmitted diseases (including gonorrhoea, chlamydia, mycoplasma or trichomonas, but not including 
HIV/AIDS), symptoms of acute or chronic epididymitis; 
(4) Residual urine volume≥100 mL; 
(5) Qmax≤15mL/s; 
(6) During previous 4 weeks used androgen hormone inhibitors (finasteride), alpha-blockers 
(terazosin, doxazosin mesylate. tamsulosin hydrochloride), antibiotics (ciprofloxacin hydrochloride), or 
any other prostatitis-specific medication (including herbal and Chinese medicine). 
III. What do you do next, if you decide to participate? 
Before your enrollment in the study, your medical history will be collected and you will receive a 
series of examinations to determine whether you are eligible to participate in the study, including 
physical examination, urinalysis and a urine culture, collection of expressed prostatic secretion, 
abdominal ultrasound, prostate ultrasound, serum PAS testing and urinary flow rate (certain patients 
may also need to receive cystoscopy). You will also need to complete a series of questionnaires to 
assess the severity of the disease and the influence on quality of life. 
2. If the results of the above screening examinations meet the inclusion criteria and you are willing 
to participate in this study, you will be invited to continue study participation in the following steps: 
(1) Based on the random number generated from the computer, the doctor will assign you to either 

 24 / 34 
 
the traditional acupuncture or sham acupuncture group. Participants in the traditional acupuncture 
group will receive deep needling on the Zhongliao (BL33), Huiyang (BL35), Shenshu (BL23), and 
Sanyinjiao (SP6) for 30 min; participants in the sham acupuncture group will receive minimally 
invasive, superficial needle insertion of 2-3mm on the sham Zhongliao (BL33), Huiyang (BL35), 
Shenshu (BL23), and Sanyinjiao (SP6). 
(2) In the study, Hwato brand disposable needles (Suzhou Medical Appliance, Jiangsu, China, 
Jiangsu Food, Drug, and Medical Appliance Administration production approval No.: 2001–0020, 
Registration No:2270202 in Year 2004) will be used.  
(3) The duration of this study is 34 weeks in total for a patient including 2-week baseline assessment, 
8-week treatment, and 24-week follow up. Frequency and duration of acupuncture: 3 sessions per week 
in weeks 1-4, and 2 sessions per week in weeks 5-8. The participants will receive 20 sessions of 
treatment in total. 
(4) During the study period, you need to complete the questionnaires faithfully. 
3. Other requirements for your cooperation 
As a participant of this study, you will have some relevant responsibilities, such as adherence to the 
schedule for examination, treatment, and clinical follow-up. Additionally, you are also responsible for 
reporting any changes in your physical and mental status to your doctor during the study process 
regardless of whether you think these changes are related to the study or not. You should follow the 
scheduled appointments with the doctor to come to the hospital for treatment. Your follow-up is very 
important because the doctor will determine whether the treatment that you are receiving really works 
and their safety profile.  
During the study, you are not allowed to use other treatments for CP/CPPS. However, if you use, 
please inform the doctor the treatment you received in detail. Every use of specialized treatment should 
be recorded as required. 
IV. Potential benefits of study participation 
You may benefit from this study. The benefits may include improvement of symptoms, even by sham 
acupuncture. The study may also help doctors and researchers to further evaluate the efficacy of 
acupuncture for CP/CPPS. The information will be beneficial in the management of other patients with 
a similar condition in the future. If you decide to participate in the study, you will get relevant physical 
and biochemical examination as well the study intervention for free during the study period. 
V. Potential side effects, risks, discomforts, and inconveniences 
The doctors will make every effort to prevent and treat any side effects brought on by this study. 
During treatment, you may feel soreness, numbness, heavy, distension sensation, etc., which are normal 
reactions to acupuncture. Acupuncture treatment may have some adverse effects, but it is rare and mild. 
You may feel fainting due to your individual physique or emotional stress when receive acupuncture 
needling. Your symptoms should be relieved after the cessation of acupuncture treatment and rest. 
Bleeding, hematoma, and other phenomena may occur after acupuncture treatment, and these 
phenomena should disappear after applying local pressure. If infection occurs in the needle site, your 
doctor will handle it timely. With the treatment following the study protocol in the study, if you 
experience adverse reactions and events related to acupuncture treatment, please feel free to call your 
doctor for help. The doctor will provide you timely treatment. If injuries have been confirmed and are 
caused by adverse reactions and events of the study, the study group will deal with them appropriately 
in accordance with relevant provisions. If you experience any discomfort or new change of your 
symptoms, or any other unforeseen circumstances during study period, regardless of whether these 

 25 / 34 
 
events are relevant with treatment of the study or not, you shall promptly notify your doctor, and he / 
she will evaluate the condition and give you appropriate medical treatment. 
VI. Payments/compensation for participation 
If you participate in the study, during the study, you will get relevant physical and biochemical 
examination and acupuncture treatment for free. If adverse events occur during the study, they will be 
managed accordingly by medical experts who will also identify whether they are related to the study or 
not. The treatment and examination required for your concomitant diseases nonrelated to the study will 
not be free of charge. 
VII. Confidentiality of personal information 
All the information related to your participation in this study will be kept confidential by the institute 
where your participation takes place. Only the institutes responsible for the study, clinical research 
institutes, and ethics committees may have access to your medical records. Your name will not appear 
in any publication or report related to this study. We will make every effort to protect the privacy of 
your personal medical information as per legal requirements and laws. 
VIII. How to acquire extra information? 
You can ask any questions about the study at any time and will get answers timely. If we notice any 
new information that may affect your willingness and decision to continue participating in the study, 
the doctor will keep you informed 
IX. Can you voluntarily choose to participate in or withdraw from the study? 
Whether to participate in this study or not entirely depends on your desire. You can refuse to 
participate in the study, or withdraw from the study at any time during the study, which will not affect 
the relationship between you and your doctor and will not affect your medical interests or interests in 
other areas. For the consideration of your best interests, doctors or researchers may terminate your 
participation in this study at any time. If you withdraw from the study for any reason, you may be 
asked for information related of acupuncture treatment or the use of other medications during your 
participation of the study. If the doctor considers it necessary, you may also be asked to have some 
laboratory tests and physical examinations performed. 
X. What you need to do now? 
Decide whether to participate in this study or not. Before you make the decision to participate in the 
study, please ask your doctor if you have any concerns. 
Thank you for reading the above information. If you decide to participate in this study, please tell your 
doctor, he / she will help you make arrangement for the study. 
Please keep this document for your own record. 
Informed Consent: Signature Page 
Study title: Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled 
trial 
Organizer of this study: Guang’anmen Hospital, China Academy of Chinese Medical Sciences 
Collaborative institute: 
Statement of agreement: 
I have read the above information about this study and have the opportunity to discuss this study 
with my doctor and ask questions. All my questions were answered satisfactorily. I understand the 
potential risks and benefits from participation in this study. I understand the participation of the study is 
voluntary and I confirm that I was given sufficient time for consideration of study participation. I 
confirm that I understand that: 

 26 / 34 
 
I can always ask the doctor for additional/more information. 
I can withdraw from the study at any time without discrimination or retaliation and my medical 
treatment and interests will not be affected. 
I understand that if I withdraw from the study, I will tell the doctor the changes of my disease 
condition and complete the relevant physical and biochemical examinations if needed, which will be 
very helpful for the whole study. 
If I need to take any other medications due to the changes of my medical condition, I will seek 
medical advice from the doctor beforehand or afterwards tell the doctor truthfully. 
I agree to allow the research institute, collaborative institutes, and ethics committees to inspect the 
data relevant to my study participation. 
I will receive a signed and dated copy of the informed consent form. 
Finally, I decide and agree to participate in this study and ensure the adherence to doctor’s orders to 
the best I can. 
Signature of patient:                                    Year month day 
Telephone: 
I confirm that I have explained this study in detail to the patient, including patient’s rights as well as 
the potential benefits and risks, and have given the patient a signed copy of the informed consent form. 
Signature of doctor: Year month day 
Office phone number of doctor:

 27 / 34 
 
Appendix 2 Outcome Assessment Tools 
List of the outcome assessment tools:  
National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) 
International Prostate Symptom Score (IPSS)  
Hospital Anxiety and Depression Scale (HADS) 
International Index of Erectile Function 5 (IIEF-5) 
European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) 
Expectation Assessment 

 28 / 34 
 
National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) 
Pain or Discomfort 
1. In the last week, have you experienced any 
pain or discomfort in the following areas? 
a. Area between rectum and testicles (perineum) 
b. Testicles 
c. Tip of the penis (not related to urination) 
d. Below your waist, in your pubic or bladder 
area 
 
2. In the last week, have you experienced: 
a. Pain or burning during urination? 
b. Pain or discomfort during or after sexual 
climax (ejaculation)? 
 
Yes 
 
□1 
□1 
□1 
□1 
 
 
Yes 
□1 
□1 
 
 
No 
 
□0 
□0 
□0 
□0 
 
 
No 
□0 
□0 
 
6. How often have you had to urinate again less than two 
hours after you finished urinating, over the last week? 
□0 Not at all 
□1 Less than 1 time in 5 
□2 Less than half the time 
□3 About half the time 
□4 More than half the time 
□5 Almost always 
 
Impact of Symptoms 
7. How much have your symptoms kept you from doing 
the kinds of things you would usually do, over the last 
week? 
□0 None 
□1 Only a little 
□2 Some 
□3 A lot 
 
8. How much did you think about your symptoms, over 
the last week? 
□0 None 
□1 Only a little 
□2 Some 
□3 A lot 
 
Quality of Life 
9. If you were to spend the rest of your life with your 
symptoms just the way they have been during the last 
week, how would you feel about that? 
□0 Delighted 
□1 Pleased 
□2 Mostly satisfied 
□3 Mixed (about equally satisfied and dissatisfied) 
□4 Mostly dissatisfied 
□5 Unhappy 
□6 Terrible 
 
Scoring the NIH-Chronic Prostatitis Symptom Index 
Domains 
Pain: Total of items 1a, 1b, 1c, 1d, 2a, 2b, 3, and 4 
=_____ 
Urinary Symptoms: Total of items 5 and 6 =_____ 
Quality of Life Impact: Total of items 7, 8 and 9 =_____ 
 
3. How often have you had pain or discomfort in any of these 
areas over the last week? 
□0 Never 
□1 Rarely 
□2 Sometimes  
□3 Often 
□4 Usually 
□5 Always 
 
4. Which number best describes your AVERAGE pain or 
discomfort on the days that you had it, over the last week? 
□  □  □  □  □  □  □  □  □  □  □ 
0   1    2   3   4    5   6   7    8   9   10 
NO PAIN                                   PAIN AS  
BAD AS  
YOU CAN  
IMAGING 
Urination 
5. How often have you had a sensation of not emptying your 
bladder completely after you finished urinating, over the last 
week? 
□0 Not at all 
□1 Less than 1 time in 5 
□2 Less than half the time 
□3 About half the time 
□4 More than half the time 
□5 Almost always 

 29 / 34 
 
International Prostate Symptom Score (IPSS)  
 
Not 
at all 
Less than 
1 time in 
5  
Less than 
half the 
time 
About 
half the 
time 
More 
than 
half the 
time 
Almost 
always 
Your 
score 
Incomplete emptying 
Over the past month, how often 
have you had a sensation of not 
emptying your bladder completely 
after you finish urinating? 
0 
1 
2 
3 
4 
5 
Frequency 
Over the past month, how often 
have you had to urinate again less 
than two hours after you finished 
urinating? 
0 
1 
2 
3 
4 
5 
Intermittency 
Over the past month, how often 
have you found you stopped and 
started again several times when 
you urinated? 
0 
1 
2 
3 
4 
5 
Urgency 
Over the last month, how difficult 
have you found it to postpone 
urination? 
0 
1 
2 
3 
4 
5 
Weak stream 
Over the past month, how often 
have you had a weak urinary 
stream? 
0 
1 
2 
3 
4 
5 
Straining 
Over the past month, how often 
have you had to push or strain to 
begin urination? 
0 
1 
2 
3 
4 
5 
 
None 
1 time 
2 times 
3 times 
4 times 
5 times 
Nocturia 
Over the past month, many times 
did you most typically get up to 
urinate from the time you went to 
bed until the time you got up in the 
morning? 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
 

 30 / 34 
 
Hospital Anxiety and Depression Scale (HADS) 
Tick the box beside the reply that is closest to how you have been feeling in the past week. Don’t take too long 
over you replies: your immediate is best. 
1. I feel tense or 'wound up': 
8. I feel as if I am slowed down: 
3 Most of the time 
3 Nearly all the time 
2 A lot of the time 
2 Very often 
1 From time to time, occasionally 
1 Sometimes 
0 Not at all 
0 Not at all 
2. I still enjoy the things I used to enjoy: 
9. I get a sort of frightened feeling like 
'butterflies' in the stomach: 
□0 Definitely as much 
□0 Not at all 
□1 Not quite so much 
□1 Occasionally 
□2 Only a little 
□2 Quite Often 
□3 Hardly at all 
□3 Very Often 
3. I get a sort of frightened feeling as if something awful 
is about to happen: 
10. I have lost interest in my appearance: 
□3 Very definitely and quite badly 
□3 Definitely 
□2 Yes, but not too badly 
□2 I don't take as much care as I should 
□1 A little, but it doesn't worry me 
□1 I may not take quite as much care 
□0 Not at all 
□0 I take just as much care as ever 
4. I can laugh and see the funny side of things: 
11. I feel restless as I have to be on the move: 
□0 As much as I always could 
□3 Very much indeed 
□1 Not quite so much now 
□2 Quite a lot 
□2 Definitely not so much now 
□1 Not very much 
□3 Not at all 
□0 Not at all 
5. Worrying thoughts go through my mind: 
12. I look forward with enjoyment to things: 
□3 A great deal of the time 
□0 As much as I ever did 
□2 A lot of the time 
□1 Rather less than I used to 
□1 From time to time, but not too often 
□2 Definitely less than I used to 
□0 Only occasionally 
□3 Hardly at all 
6. I feel cheerful: 
13. I get sudden feelings of panic: 
□3 Not at all 
□3 Very often indeed 
□2 Not often 
□2 Quite often 
□1 Sometimes 
□1 Not very often 
□0 Most of the time 
□0 Not at all 
7. I can sit at ease and feel relaxed: 
14. I can enjoy a good book or radio or TV 
program: 
□0 Definitely 
□0 Often 
□1 Usually 
□1 Sometimes 
□2 Not Often 
□2 Not often 
□3 Not at all 
□3 Very seldom 

 31 / 34 
 
International Index of Erectile Function 5 (IIEF-5)  
1. How do you rate your confidence that you could get 
and keep an erection? 
 
□0 No confidence 
□1 Very low 
□2 Low  
□3 Moderate 
□4 High  
□5 Very high 
2. When you had erections with sexual stimulation, how 
often were your erections hard enough for penetration? 
 
□0 No sexual activity 
□1 Almost never/never 
□2 A few times (much less than half the time) 
□3 Sometimes (about half the time) 
□4 Most times (much more than half the time) 
□5 Almost always/always 
3. During sexual intercourse, how often were you able to 
maintain your erection after you had penetrated (entered) 
your partner? 
 
□0 No sexual intercourse 
□1 Almost never/never 
□2 A few times (much less than half the time) 
□3 Sometimes (about half the time) 
□4 Most times (much more than half the time) 
□5 Almost always/always 
4. During sexual intercourse, how difficult was it to 
maintain your erection to completion of intercourse? 
 
□0 No sexual intercourse 
□1 Extremely difficult 
□2 Very difficult 
□3 Difficult  
□4 Slightly difficult 
□5 Not difficult 
5. When you attempted sexual intercourse, how often 
was it satisfactory for you? 
 
□0 No sexual intercourse 
□1 Very low 
□2 Low  
□3 Moderate 
□4 High  
□5 Very high 

 32 / 34 
 
European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) 
MOBILITY 
 
I have no problems in walking about 
□ 
I have slight problems in walking about 
□ 
I have moderate problems in walking about 
□ 
I have severe problems in walking about 
□ 
I am unable to walk about 
□ 
SELF-CARE 
 
I have no problems washing or dressing myself 
□ 
I have slight problems washing or dressing myself 
□ 
I have moderate problems washing or dressing myself 
□ 
I have severe problems washing or dressing myself 
□ 
I am unable to wash or dress myself 
□ 
USUAL ACTIVITIES (e.g. work, study, housework, family or leisure activities) 
 
I have no problems doing my usual activities 
□ 
I have slight problems doing my usual activities 
□ 
I have moderate problems doing my usual activities 
□ 
I have severe problems doing my usual activities 
□ 
I am unable to do my usual activities 
□ 
PAIN/DISCOMFORT 
 
I have no pain or discomfort 
□ 
I have slight pain or discomfort 
□ 
I have moderate pain or discomfort 
□ 
I have severe pain or discomfort 
□ 
I am extreme pain or discomfort 
□ 
ANXIETY/DEPRESSION 
 
I am not anxious or depressed 
□ 
I am slightly anxious or depressed 
□ 
I am moderately anxious or depressed 
□ 
I am severely anxious or depressed 
□ 
I am extreme anxious or depressed 
□ 
 
 
 
 
 
 
 
 
 

 33 / 34 
 
Expectation Assessment  
In general, is acupuncture effective for controlling the illness? 
□ Yes  
□ No 
□ Unclear 
Do you think acupuncture will be helpful to improve your CP/CPPS symptoms 
□ Yes  
□ No 
□ Unclear 

Acupuncture for Chronic 
Prostatitis/Chronic Pelvic Pain 
Syndrome 
Statistical Analysis Plan (SAP) 
NCT number: NCT03213938 
September 4, 2017 
Prepared by an Independent Statistician: 
Yan Liu (Statistician), Data Centre of Traditional Chinese Medicine, China Academy 
of Chinese Medical Sciences 

Content 
1. Introduction .......................................................................................................................................... 1 
2. Study Objective .................................................................................................................................... 4 
3. Design ................................................................................................................................................... 4 
3.1 Overview ........................................................................................................................................ 4 
3.2 Eligibility criteria ............................................................................................................................ 4 
3.2.1 Inclusion Criteria ..................................................................................................................... 4 
3.2.2 Exclusion criteria ..................................................................................................................... 4 
4. Schedule of Evaluation ......................................................................................................................... 5 
5. Efficacy and Safety outcomes .............................................................................................................. 6 
5.1 Efficacy outcomes .......................................................................................................................... 6 
5.1.1 Primary Outcomes ................................................................................................................... 6 
5.1.2 Secondary Outcomes ............................................................................................................... 6 
5.2 Safety outcomes .............................................................................................................................. 7 
6. Statistical Considerations ..................................................................................................................... 7 
6.1 Study hypothesis ............................................................................................................................. 7 
6.2 Study Populations ........................................................................................................................... 7 
6.3 Statistical Analyses ......................................................................................................................... 7 
6.3.1 The general principle ............................................................................................................... 7 
6.3.2 Demographics and Baseline Characteristics ............................................................................ 8 
6.3.3 Analyses for Primary Outcome ................................................................................................ 8 
6.3.4 Analyses for Secondary Outcome ............................................................................................ 8 
6.3.5 Safety Analyses ....................................................................................................................... 9 
References: ............................................................................................................................................... 9 

1. Introduction 
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to the presence of bothersome 
pelvic pain symptoms without an identifiable cause1. Table 1 illustrates the 4 categories of prostatitis 
per the National Institutes of Health (NIH) classification of prostatitis syndromes. CP/CPPS affects 
approximately 10–16% of men worldwide1-4. Men of all ages can be impacted, among whom those 
aged 36–50 years are the most commonly affected5. There is no apparent racial predisposition to this 
disease.  
Common symptoms of CP/CPPS include discomfort in the perineum, suprapubic region, and lower 
urinary tract symptoms6. Patients with CP/CPPS also frequently experience a wide array of sexual 
dysfunctions, including erectile dysfunction (ED), painful ejaculation and premature ejaculation (PE)7-
11, on top of symptoms suggestive of negative cognition or emotional consequences12. The 
aforementioned symptoms negatively impact upon the patient’s quality of life (QoL) to a similar degree 
or worse than those of congestive heart failure, Crohn’s disease, diabetes mellitus or angina13, 14. 
Because of its high prevalence and lack of effective therapies, direct and indirect costs associated with 
CP/CPPS are substantial15. Approximately 25% of men experience loss of work and approximately 
50% have reduced leisure time at some point due to CP/CPPS16. The direct and indirect cost of care in 
China approaches 8059 CNY per person in 200917, and data indicate that in the USA, the total annual 
cost for patients with prostatitis was US$4387 in 200615.  
Unlike acute/chronic bacterial prostatitis, the cause of CP/CPPS is unknown and no well-conducted 
epidemiologic studies are available to support any particular risk factors18. The diagnosis of CP/CPPS 
is mainly based on symptoms. Treatments for CP/CPPS usually include alpha-blockers, antibiotics, 
nonsteroidal anti-inflammatory drugs (NSAIDs), and phytotherapy. Alpha-blockers and antibiotics 
have moderate effects on pain, voiding and QoL19. Both alpha-blockers and antibiotics are 
recommended for patients with CP/CPPS for less than 1 year, but only antibiotics are recommended in 
treatment-naïve patients. NSAIDs and phytotherapy are less commonly used, because of lack of 
research evidence19. Although advances have been made in research and developing novel treatment 
options, definitive treatments for CP/CPPS are still lacking19. Besides, pharmacological interventions 
are accompanied with adverse effects such as dizziness, nausea, and postural hypotension, which also 
reduce patients’ compliance to treatments20. Previous studies suggest that acupuncture may be a 
potential treatment for CP/CPPS 21-25. However, owing to small sample sizes and other methodological 
limitations of clinical trials, the efficacy of acupuncture in CP/CPPS remains inconclusive 19, 26. In 
addition, the durable efficacy of the acupuncture is still unclear.27  
NIH consensus classification of prostatitis 
Definition 
(I) Acute bacterial prostatitis 
Acute infection of the prostate 
(II) Chronic bacterial prostatitis 
Chronic or recurrent infection of the prostate 
(III) Chronic prostatitis/chronic pelvic pain 
syndrome 
No demonstrated infection 
    A. Inflammatory 
Leukocytes in expressed prostatic secretions, post 
prostate massage urine, or semen 
    B. Noninflammatory 
No evidence of inflammation 
(IV) Asymptomatic inflammatory 
prostatitis 
No subjective symptoms detected, inflammation 
shown either by prostate biopsy or the presence of 
leukocytes in EPS/semen during evaluation for 
infertility or other disorders 

Table 1. NIH consensus classification and definition of 4 categories of prostatitis1 
2. Study Objective 
The objective of this multi-center, randomized, sham acupuncture-controlled trial is to assess the 
effectiveness, especially the long-term efficacy of acupuncture for relieving symptoms of CP/CPPS.  
3. Design 
3.1 Overview 
This is a multicenter, participants-blinded, parallel-group, randomized controlled study conducted in 
China. 
The participants will be recruited in 10 clinical sites, which are Dongfang Hospital Beijing 
University of Chinese Medicine; Beijing Fengtai Hospital of Integrated Traditional and Western 
Medicine; West China Hospital of Sichuan University; The Third Affiliated Hospital of Zhejiang 
Chinese Medical University; The First Affiliated Hospital of Anhui University of Chinese Medicine; 
Hengyang Hospital Affiliated to Hunan University of Chinese Medicine; The First Hospital of Hunan 
University of Chinese Medicine; Guangdong Provincial Hospital of Traditional Chinese Medicine; 
Yantai Hospital of Traditional Chinese Medicine; and Shaanxi Provincial Hospital of Traditional 
Chinese Medicine. Guang’anmen Hospital, China Academy of Chinese Medical Sciences will be 
responsible for study design and organization. A data coordination center will be established at China 
Academy of Chinese Medical Sciences (CACMS) to monitor data management. 
3.2 Eligibility criteria 
3.2.1 Inclusion Criteria 
(1) History of pain perceived in the prostate region and absence of other lower urinary tract pathology 
for a minimum of three of the past 6 months. In addition, any associated lower urinary tract 
symptoms, sexual function, and psychological factors should be addressed. Physical examinations, 
urinary analyses, and urine cultures will be performed for all subjects; 
(2)  Age 18 to 50 years; 
(3)  NIH-CPSI total score≥15. 
3.2.2 Exclusion criteria 
(1) Other types of prostatitis, such as acute bacterial prostatitis, chronic bacterial prostatitis, or 
asymptomatic inflammatory prostatitis; 
(2) Urinary tract infection with a urine culture value >100,000 colony forming units (CFU)/mL, 
clinical evidence of urethritis, including urethral discharge or positive culture, diagnostic of 
sexually transmitted diseases (including gonorrhoea, chlamydia, mycoplasma or trichomonas, but 
not including HIV/AIDS), symptoms of acute or chronic epididymitis; 
(3) Prostate, penile, testicular, bladder, or urethral cancer, seizure disorder in any medical history; 
(4) Inflammatory bowel disease, active urethral stricture, bladder outlet obstruction, neurologic 
disease or disorder affecting the bladder, neurologic impairment or psychiatric disorder preventing 
understanding of consent and self-report scale; 
(5) Overactive bladder, neurogenic bladder, interstitial cystitis, glandular cystitis; 
(6) Organic disease of the urinary system; 
(7) Severe cardiac, lung, cerebrum, liver or renal system disease, or hematopoietic system disease; 
(8) Residual urine volume≥100 mL; 
(9) Qmax≤15mL/s; 
(10) During previous 4 weeks prior to study participation, used androgen hormone inhibitors 
(finasteride), alpha-blockers (terazosin, doxazosin mesylate. tamsulosin hydrochloride), antibiotics 

(ciprofloxacin hydrochloride), or any other prostatitis-specific medication (including herbal and 
Chinese medicine)  
4. Schedule of Evaluation 
Table 2. Enrolment, Intervention and Evaluation Schedules 
Abbreviations: NIH-CPSI National Institutes of Health Chronic Prostatitis Symptom Index, IIEF-5 
International Index of Erectile Function 5, HADS Hospital Anxiety and Depression Scale, GRA Global 
Response Assessment, EQ-5D-5L Five-level EuroQol five-dimensional questionnaire, VAS visual 
analogue scale 
 
STUDY PERIOD 
 
Enrolment 
Allocation 
Treatment 
Follow-
up 
TIMEPOINT (W, week) 
-2 and -1 
0 
1 
2 
3 
4 
5 
6 
7 
8 
20 
32 
Enrolment 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
× 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
× 
 
 
 
 
 
 
 
 
 
 
 
Demography characteristics 
× 
 
 
 
 
 
 
 
 
 
 
 
Allocation 
 
× 
 
 
 
 
 
 
 
 
 
 
Interventions 
 
 
 
 
 
 
 
 
 
 
 
 
Acupuncture 
 
 
× 
× 
× 
× 
× 
× 
× 
× 
 
 
Sham acupuncture 
 
 
× 
× 
× 
× 
× 
× 
× 
× 
 
 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
Proportion of responders 
 
 
 
 
 
 
 
 
 
× 
 
× 
NIH-CPSI 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
IPSS 
× 
 
 
 
 
× 
 
 
 
× 
× 
× 
IIEF-5 
× 
 
 
 
 
 
 
 
 
× 
× 
× 
HADS 
× 
 
 
 
 
 
 
 
 
× 
× 
× 
EQ-5D-5L 
× 
 
 
 
 
 
 
 
 
× 
× 
× 
GRA 
 
 
 
 
 
× 
 
 
 
× 
× 
× 
Expectation assessment 
× 
 
 
 
 
 
 
 
 
 
 
 
Urinary flow rate 
× 
 
 
 
 
 
 
 
 
× 
 
× 

5. Efficacy and Safety outcomes  
5.1 Efficacy outcomes  
5.1.1 Primary Outcomes 
The two co-primary outcomes include the proportions of responders at week 8 and week 32. The 
responder is defined as a participant with a decline of 6 points or more from baseline in the total score 
of the Chinese version NIH-CPSI. As a validated, self-reported questionnaire, NIH-CPSI is widely 
used to assess CP/CPPS symptoms28, 29. NIH-CPSI consists of 9 items divided into 3 discrete domains: 
pain (0–21 points), urinary symptoms (0–10 points) and QoL (0–12 points), with a total score of 0–43 
points (a higher score indicates worse symptoms). A decline of at least 6 points in NIH-CPSI has been 
identified as the minimal clinically important difference (MCID)25.  
5.1.2 Secondary Outcomes 
(1) Proportion of responders during weeks 1-7, and at week 20.  
The NIH-CPSI will be assessed once a week during treatment, and at week 20 and week 32. The 
responder is defined as who has a decline of 6 or more than 6-point from baseline measured by using 
the NIH-CPSI. 
(2) The change from baseline in NIH-CPSI total score during weeks 1-8, at week 20, and at week 32. 
(3) The change from baseline in NIH-CPSI subscales (pain, urinary symptoms and QoL) during weeks 
1-8, at week 20, and at week 32. 
(4) The change from baseline in IPSS at week 4, week 8, week 20, and week 32. 
IPSS is a valid, reliable and sensitive measure for patients with lower urinary tract symptoms (LUTS); 
it is widely used in clinical practice and research to determine the severity of LUTS, including 
incomplete bladder emptying, frequency of urination, intermittency, urgency, weak urine stream, 
straining and nocturia30, 31. Each of the questions is rated from 0 (not at all) to 5 (almost always); 
severity of LUTS can be graded as mild (0–7), moderate (8–19) or severe (20–35). IPSS will be 
assessed at the end of the 4th, 8th, 20th, and 32nd week. 
(5) The change from baseline in HADS at week 8, week 20, and week 32. 
HADS will be assessed at the end of the week 8, week 20, and week 32. HADS is made up of 7 items 
for the assessment of depression and anxiety; the completion of this scale usually requires 2–5 
minutes32. 
(6) The change from baseline in IIEF-5 at week 8, week 20, and week 32. 
Chinese version IIEF-5 will be assessed at the end of the week 8, week 20, and week 32. The IIEF-5 
consists of 15 items in 5 domains with a total score ranging from 5 to 25 (mild ED, 12-21; moderate 
ED, 8-11; severe ED, 5-7); it is a psychometrically valid and reliable instrument with high 
sensitivity and specificity for detecting treatment effects in patients with ED of a broad  
spectrum of aetiology33. 
(7) The change from baseline in EQ-5D-5L at week 8, week 20, and week 32. 
The EQ-5D-5L will be assessed at the end of week 8, week 20, and week 32. The EQ-5D-5L is a 
generic instrument designed for self-completion and postal surveys; it is well-established and suitable 
for evaluation of QoL in participants with CP/CPPS34. 
(8) The proportions of participants in each response category of the Global Response Assessment 
(GRA) at week 4, week 8, week 20, and week 32. 
The proportions of participants in each response category of the GRA in the two groups after treatment 
will be measured at the end of the week 4, week 8, week 20, and week 32. GRA consists of 7 response 
categories: markedly worsened, moderately worsened, slightly worsened, no change, slightly improved, 

moderately improved, and markedly improved. We will identify a participant who reports “moderate” 
or “marked improvement” as a responder35.  
(9) The change for peak and average urinary flow rates from baseline at weeks 8 and 32. 
Peak and average urinary flow rates will be measured at weeks 8 and 32. 
(10)  Expectation assessment at baseline 
Expectation assessment will be assessed at baseline, which includes two brief questions to investigate 
whether patients are confident that acupuncture treatment will help their CP/CPPS: “In general, is 
acupuncture effective for controlling the illness?”, “Do you think acupuncture will be helpful to 
improve your CP/CPPS symptoms?” For each question, participants could choose “Yes”, “No” or 
“Unclear” as the answer. 
5.2 Safety outcomes 
According to their potential association with the treatment, AEs will be categorized as treatment-
related or non-treatment-related within 24 hours after their occurrence. Treatment-related adverse 
events include pain, haematoma, localized infection, broken needle, fainting, nausea, headache, 
dizziness, insomnia, vomiting, or palpitations during or after treatment.  
Serious adverse events will be defined as events requiring hospitalization, causing disability or 
impaired ability to work, threatening life or resulting in death. 
All the adverse events and serious adverse events, whether related to acupuncture or not, will be 
reported and documented.  
6. Statistical Considerations 
6.1 Study hypothesis 
The primary study hypothesis is that acupuncture is more effective than sham acupuncture in 
relieving symptoms of CP/CPPS. 
6.2 Study Populations 
All patients with randomization will be included in the analysis set regardless of whether they 
receive any treatment. According to the intention-to-treat principle, all analysis will be based on the 
randomization set. 
6.3 Statistical Analyses 
6.3.1 The general principle 
Summary Statistics 
Summary tables (descriptive statistics and/or frequency tables) will be provided for all variables at 
different endpoints. For continuous variables, means and standard deviations will be presented, unless 
the variable has a skewed distribution, in which case medians, 25th and 75th percentiles will be 
presented. For categorical variables, the number and percentage of participants within each category 
will be presented. For each variable (continuous or categorical), the number of missing values will be 
reported. 
Statistical Comparisons Between Groups 
Continuous variables will be compared using a two-sample t-test or Wilcoxon rank-sum test if data 
show serious deviations from a normal distribution. Categorical data or ordinal data will be compared 
using a Wilcoxon rank-sum test, chi-square test or Fisher’s exact test, as appropriate. All tests will be 
two-sided. 
For the analysis of the primary and secondary outcomes, estimated treatment differences and 
associated 95% two-sided confidence intervals will be presented. 
Multiple Comparisons 

Since only one co-primary outcome is defined, no adjustments to the significance level will be required 
to account for multiple testing.  
For the analysis of the secondary and safety outcomes, no adjustment for multiple comparisons will 
be made. 
Analysis Software 
For all statistical analyses, SAS 9.4 software will be used. All hypothesis testing will be carried out at 
the 5% (2-sided) significance level. 
6.3.2 Demographics and Baseline Characteristics 
All data recorded at baseline will be summarized by group. Comparisons between groups will be 
performed using the methodology described in section 6.3.1. Summaries will be presented for the ITT 
Set in both groups. 
6.3.3 Analyses for Primary Outcome 
Primary outcome analysis will be conducted with a logistic generalized linear mixed model (GLMM) 
for repeated measures. Responder or non-responder at each scheduled post-baseline visit (end of 
treatment, and 20 and 24 weeks after treatment) is the dependent variable. Subjects who discontinue 
without providing the NIH-CPSI score will be considered as non-responders. The logistic GLMM is 
fitted using the logit link and the binomial distribution. The model will include the baseline NIH-CPSI 
total score as a fixed-effect covariate, with treatment group (acupuncture and sham acupuncture), visit 
and treatment × visit interaction as fixed-effect categorical factors. The interaction will remain in the 
model regardless of significance. Treatment group comparisons at each visit will be estimated by 
differences between least squares means from the treatment × visit interaction, and will be presented as 
odds ratios with accompanying p values and 95% CIs. The predicted probability of response at each visit 
will also be presented. Such models provide fairly robust results for treatment comparisons when 
longitudinal binary responses are missing, with an assumption that data are missing at random(MAR), 
according to reported values36.  
Sensitivity Analyses for the Primary Outcome 
Because the MAR assumption cannot be verified using the data, the sensitivity of inferences to 
departures from the MAR assumption should be tested37. A straightforward sensitivity analysis for the 
MAR assumption in multiple imputation is based on the control-based pattern imputation model under 
the MNAR assumption by using the SAS procedure Proc MI process. Therefore, mixed-effect model 
under MNAR assumption will be used. 6.3.4 Analyses for Secondary Outcome 
Efficacy analyses for all secondary outcomes will be performed in the ITT population, without 
imputation of missing data. 
Continuous data will be described with the average, standard deviation, median, minimum value, and 
maximum value, whereas categorical data will be represented by percentages as appropriate. Changes 
from baseline in the NIH-CPSI total score will be analyzed using linear mixed-effects model. The model 
will include the observed change from baseline score at each assessment point as the dependent variable; 
the baseline value, treatment group (acupuncture and sham acupuncture), visit and treatment × visit 
interaction as fixed effects. Treatment group comparisons at each visit will be estimated by differences 
between least squares means from the treatment × visit interaction, with accompanying p values and 95% 
CIs. Log-transformation may be applied in the case of serious violations of the model assumptions 
(normality and constant variance of the residuals). If not appropriate, the Wilcoxon rank-sum test will be 
used. The effect of the treatment will be estimated by the difference (or ratio, in the case of log-
transformation) between treatments and will be presented along with its associated 95% CI. The same 

approach will be used in other longitudinal continuous outcomes such as NIH-CPSI subscale scores (pain, 
urinary symptoms, and QoL).  
Other categorical data or ordinal data will be compared between groups using the Wilcoxon rank-sum 
test, chi-square test or Fisher’s exact test, as appropriate. The James and Bang blinding indices will be 
used to assess the success of blinding. The James blinding index is a variation on the statistic in which 1 
represents perfect blinding. The Bang blinding index for each group represents the proportion of 
participants making a correct treatment guess beyond chance; 0 represents perfect blinding, a positive 
index indicates a correct guess, and a negative index indicates a guess in the opposite direction. 
6.3.5 Safety Analyses 
All adverse events and serious adverse events will be listed. Adverse events include the acupuncture-
related adverse events and other adverse events. Chi-square test or Fisher’s exact test will be used to 
compare the incidence of adverse events between the acupuncture and sham acupuncture groups. P-value 
will not be adjusted for multiple tests. 
 
References: 
1. 
Krieger JN, Nyberg L, Nickel JC. NIH consensus definition and classification of prostatitis. 
Jama-Journal of the American Medical Association 1999;282:236-237. 
2. 
Nickel JC, Downey J, Hunter D, et al. Prevalence of prostatitis-like symptoms in a population 
based study using the National Institutes of Health chronic prostatitis symptom index. Journal 
of Urology 2001;165:842-845. 
3. 
Collins MM, Meigs JB, Barry MJ, et al. Prevalence and correlates of prostatitis in the health 
professionals follow-up study cohort. J Urol 2002;167:1363-6. 
4. 
Roberts RO, Jacobson DJ, Girman CJ, et al. Prevalence of prostatitis-like symptoms in a 
community based cohort of older men. J Urol 2002;168:2467-71. 
5. 
Litwin MS, McNaughton-Collins M, Fowler FJ, et al. The National Institutes of Health Chronic 
Prostatitis Symptom Index: Development and Validation of a New Outcome Measure. Journal 
of Urology 1999;162:369-375. 
6. 
Rees J, Abrahams M, Doble A, et al. Diagnosis and treatment of chronic bacterial prostatitis and 
chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline. Bju International 
2015;116:509-525. 
7. 
Bartoletti R, Cai T, Mondaini N, et al. Prevalence, incidence estimation, risk factors and 
characterization of chronic prostatitis/chronic pelvic pain syndrome in urological hospital 
outpatients in Italy: results of a multicenter case-control observational study. J Urol 
2007;178:2411-5; discussion 2415. 
8. 
Lee SW, Liong ML, Yuen KH, et al. Adverse impact of sexual dysfunction in chronic 
prostatitis/chronic pelvic pain syndrome. Urology 2008;71:79-84. 
9. 
Hao ZY, Li HJ, Wang ZP, et al. The prevalence of erectile dysfunction and its relation to chronic 
prostatitis in Chinese men. J Androl 2011;32:496-501. 
10. 
Chung SD, Keller JJ, Lin HC. A case-control study on the association between chronic 
prostatitis/chronic pelvic pain syndrome and erectile dysfunction. BJU Int 2012;110:726-30. 
11. 
Tran CN, Shoskes DA. Sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome. 
World J Urol 2013;31:741-6. 
12. 
Tripp DA, Nickel JC, Wang Y, et al. Catastrophizing and pain-contingent rest predict patient 
adjustment in men with chronic prostatitis/chronic pelvic pain syndrome. J Pain 2006;7:697-

708. 
13. 
Collins MM, Pontari MA, O'Leary MP, et al. Quality of life is impaired in men with chronic 
prostatitis. The chronic prostatitis collaborative research network. Journal of Urology 
2002;168:395-396. 
14. 
Wenninger K, Heiman JR, Rothman I, et al. Sickness impact of chronic nonbacterial prostatitis 
and its correlates. J Urol 1996;155:965-8. 
15. 
JQ C. Male chronic pelvic pain syndrome: Prevalence, risk factors, treatment patterns, and 
socioeconomic impact. Curr Prostate Rep 2008;6. 
16. 
Calhoun EA, McNaughton Collins M, Pontari MA, et al. The economic impact of chronic 
prostatitis. Arch Intern Med 2004;164:1231-6. 
17. 
Liang CZ, Li HJ, Wang ZP, et al. Treatment of chronic prostatitis in Chinese men. Asian J Androl 
2009;11:153-6. 
18. 
McNaughton Collins M, MacDonald R, Wilt TJ. Diagnosis and treatment of chronic abacterial 
prostatitis: a systematic review. Ann Intern Med 2000;133:367-81. 
19. 
Engeler DS BA, Dinis-Oliveira P, Elneil S, Hughes J, Messelink EJ, et al. The 2013 EAU 
guidelines on chronic pelvic pain: is management of chronic pelvic pain a habit, a philosophy, 
or a science? 10 years of development. European Urology 2013;64:431-9. 
20. 
McNaughton C, Mac Donald R, Wilt T. Interventions for chronic abacterial prostatitis. 
Cochrane Database Syst Rev 2001:CD002080. 
21. 
Lee SWH, Liong ML, Yuen KH, et al. Acupuncture versus sham acupuncture for chronic 
prostatitis/chronic pelvic pain. American Journal of Medicine 2008;121. 
22. 
Lee S-H, Lee B-C. Electroacupuncture Relieves Pain in Men With Chronic Prostatitis/Chronic 
Pelvic Pain Syndrome: Three-arm Randomized Trial. Urology 2009;73:1036-1041. 
23. 
Qin Z, Wu J, Tian J, et al. Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-
blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Sci Rep 
2016;6:35737. 
24. 
Qin Z, Wu J, Zhou J, et al. Systematic Review of Acupuncture for Chronic Prostatitis/Chronic 
Pelvic Pain Syndrome. Medicine (Baltimore) 2016;95:e3095. 
25. 
Propert KJ, Litwin MS, Wang Y, et al. Responsiveness of the National Institutes of Health 
Chronic Prostatitis Symptom Index (NIH-CPSI). Qual Life Res 2006;15:299-305. 
26. 
Khan A. Updates on therapies for chronic prostatitis/chronic pelvic pain syndrome. World 
Journal of Pharmacology 2015;4. 
27. 
Chang SC, Hsu CH, Hsu CK, et al. 9. The efficacy of acupuncture in managing patients with 
chronic prostatitis/chronic pelvic pain syndrome: A systemic review and meta-analysis. 
Neurourol Urodyn 2017;36:474-481. 
28. 
Hong K, Xu QQ, Jiang H, et al. [Chronic prostatitis symptom index of Chinese]. Zhonghua Nan 
Ke Xue 2002;8:38-41. 
29. 
Litwin MS. A review of the development and validation of the National Institutes of Health 
Chronic Prostatitis Symptom Index. Urology 2002;60:14-18. 
30. 
Szeto PS. Applilcation of the Chinese version of the international prostate symptom score for 
the management of lower urinary tract symptoms in a primary health care setting. Hong Kong 
Medical Journal 2008;14:458-464. 
31. 
Choi EP, Lam CL, Chin WY. Validation of the International Prostate Symptom Score in Chinese 
males and females with lower urinary tract symptoms. Health Qual Life Outcomes 2014;12:1. 

32. 
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 
1983;67:361-70. 
33. 
Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an abridged, 5-item 
version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile 
dysfunction. Int J Impot Res 1999;11:319-26. 
34. 
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-
level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727-36. 
35. 
Nickel JC, Krieger JN, McNaughton-Collins M, et al. Alfuzosin and symptoms of chronic 
prostatitis-chronic pelvic pain syndrome. New England Journal of Medicine 2008;359:2663-
2673. 
36. 
Frank Liu G, Zhan X. Comparisons of methods for analysis of repeated binary responses with 
missing data. J Biopharm Stat. 2011. 21(3): 371-92. 
37. 
Little RJ, D'Agostino R, Cohen ML, et al. The prevention and treatment of missing data in 
clinical trials. N Engl J Med. 2012;367(14):1355-60.