Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

• Acupuncture (Device): For acupuncture group, Hwato brand disposable acupuncture needles (size 0.30 × 75mm; size 0.30 × 40mm) will be used. Bilateral SP6, BL33, BL23, and BL35, were selected as acupoints protocol. Acupuncture group consists of 20 sessions over an 8-week period after baseline, each for 30 minutes, and will be administered over 8 weeks (3 sessions in each of the first 4 weeks, and 2 sessions in each of the remaining 4 weeks).
• Sham acupuncture (Device): For sham acupuncture group, Hwato brand disposable acupuncture needles (size 0.30 × 25mm) will be used to insert vertically about 2-3 mm without manipulation into non-acupoints bilateral sham SP6, sham BL33, sham BL23, and sham BL35, which were located at different physical locations than SP6, BL23, BL 33, and BL35. Sham acupuncture group consists of 20 sessions over an 8-week period after baseline, each for 30 minutes, and will be administered over 8 weeks (3 sessions in each of the first 4 weeks, and 2 sessions in each of the remaining 4 weeks).

Primary outcomes

• Proportion of Responders at the End of 8-week [week 8]: The responder is defined as who has a decline of 6 or more than 6-point from baseline measured by using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI).
• Proportion of Responders at the End of 32-week [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.

Secondary outcomes

• Proportion of Responders at Other Time Points [weeks 1-7; week 20]: The responder is defined as who has a decline of 6 or more than 6-point from baseline measured by using the NIH-CPSI.
• the Change From Baseline in NIH-CPSI Total Score [weeks 1-8; week 20; week 32]: The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) is a universally accepted, reliable and valid instrument recommended for clinical evaluation and research of CP/CPPS by consensus guidelines. It measures the domains of pain (score range, 0-21), urinary function (0-10) and quality of life impact (0-12) in CP/CPPS, with a total score ranging from 0 to 43 and higher scores indicating worse conditions.
• the Change From Baseline in NIH-CPSI Subscales [weeks 1-8; week 20; week 32]: The NIH-CPSI is a universally accepted, reliable and valid instrument recommended for clinical evaluation and research of CP/CPPS by consensus guidelines. It measures the domains of pain, urinary function and quality of life impact in CP/CPPS. The score range of pain subscale is 0-21, with higher scores indicating worse conditions. The score range of urinary function subscale is 0-10, with higher scores indicating worse conditions. The score range of quality-of-life subscale is 0-12, with higher scores indicating worse quality of life.
• the Change From Baseline in the International Prostate Symptom Score (IPSS) [week 4; week 8; week 20; week 32]: IPSS is a valid, reliable and sensitive measure for patients with lower urinary tract symptoms; it is widely used in clinical practice and research to determine the severity of lower urinary tract symptoms, including incomplete bladder emptying, frequency of urination, intermittency, urgency, weak urine stream, straining and nocturia. Each of the questions is rated from 0 (not at all) to 5 (almost always). IPSS score ranges from 0 to 35, with higher score indicating more severe urinary symptoms.
• the Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) [week 8; week 20; 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 minutes. HADS score ranges from 0 to 42, with higher scores indicating greater anxiety and depression.
• the Change From Baseline in the International Index of Erectile Function 5 (IIEF-5) [week 8; week 20; week 32]: The IIEF-5 is a psychometrically valid and reliable instrument with high sensitivity and specificity for detecting treatment effects in patients with erection dysfunction of a broad spectrum of aetiology. Chinese version IIEF-5 score ranges from 0 to 25, with lower scores indicating greater severity of dysfunction and minimal clinical important difference over 5.
• the Change From Baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire [week 8; week 20; week 32]: The EQ-5D-5L is a well-established and suitable for evaluation of quality of life in participants with CP/CPPS. EQ-5D-5L overall index ranges from -0.39 to 1.00, with higher overall index indicating better generic health-status.
• the Proportions of Participants in Each Response Category of the Global Response Assessment (GRA) [week 4; week 8; week 20; week 32]: GRA consists of 7 response categories: markedly worsened, moderately worsened, slightly worsened, no change, slightly improved, moderately improved, and markedly improved.
• the Change for Peak and Average Urinary Flow Rate From Baseline [weeks 8 and 32]

Other outcomes

• Expectation Assessment [baseline]: Expectation assessment will be assessed at baseline, which includes 2 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 helpful to improve your CP/CPPS symptoms?" For each question, participants could choose "Yes", "No" or "unclear" as the answer.

Sex: Male, ages: 18 Years to 50 Years

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 Chronic Prostatitis Symptom Index (NIH- CPSI) total score ≥ 15.

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 of more than 100,000 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≥100ML.
* 5\. Qmax≤15ML/S.
* 6\. Prior 4 weeks used androgen hormone inhibitors (finasteride), alpha-blockers (terazosin HCI, doxazosin mesylate, tamsulosin hydrochloride), antibiotics (ciprofloxacin hydrochloride), or any other prostatitis-specific medication (including herb and Chinese medicine).

Participant flow

Outcome results

• Proportion of Responders at the End of 8-week (Primary), Number, percentage of participants: Acupuncture 60.6; Sham Acupuncture 36.8
• Proportion of Responders at the End of 32-week (Primary), Number, percentage of participants: Acupuncture 61.5; Sham Acupuncture 38.3
• Proportion of Responders at Other Time Points (Secondary), Number, percentage of participants: Acupuncture 9.1; Sham Acupuncture 8.3
• the Change From Baseline in NIH-CPSI Total Score (Secondary), Mean, score on a scale: Acupuncture -1.9 (-2.4 to -1.5); Sham Acupuncture -1.3 (-1.8 to -0.9)
• the Change From Baseline in NIH-CPSI Subscales (Secondary), Mean, score on a scale: Acupuncture -0.6 (-0.9 to -0.4); Sham Acupuncture -0.5 (-0.7 to -0.2)
• the Change From Baseline in the International Prostate Symptom Score (IPSS) (Secondary), Mean, score on a scale: Acupuncture -2.7 (-3.2 to -2.3); Sham Acupuncture -1.7 (-2.1 to -1.2)
• the Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) (Secondary), Mean, score on a scale: Acupuncture -1.9 (-2.5 to -1.4); Sham Acupuncture -0.8 (-1.3 to -0.3)
• the Change From Baseline in the International Index of Erectile Function 5 (IIEF-5) (Secondary), Mean, score on a scale: Acupuncture 0.8 (0.2 to 1.3); Sham Acupuncture 0.3 (-0.3 to 0.8)
• the Change From Baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire (Secondary), Mean, units on a scale: Acupuncture 0.06 (0.05 to 0.07); Sham Acupuncture 0.03 (0.02 to 0.04)
• the Proportions of Participants in Each Response Category of the Global Response Assessment (GRA) (Secondary), Number, percentage of participants: Acupuncture 15.9; Sham Acupuncture 7.5
• the Change for Peak and Average Urinary Flow Rate From Baseline (Secondary), Mean, ml/s: Acupuncture 0.6 (-0.3 to 1.6); Sham Acupuncture 0.7 (-0.2 to 1.6)
• Expectation Assessment (Other pre specified), Count of participants, Participants: Acupuncture 167; Sham Acupuncture 165

Adverse events

Time frame: 34 weeks

Other adverse events by term

• Qin Z, Liu Y, Zhou K, Wu J, Pang R, Li N, Xu C, Kwong JSW, Liu Z. Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: study protocol for a randomized controlled trial. Trials. 2017 Dec 22;18(1):616. doi: 10.1186/s13063-017-2383-8. PMID 29273095
• Results publication: Sun Y, Liu Y, Liu B, Zhou K, Yue Z, Zhang W, Fu W, Yang J, Li N, He L, Zang Z, Su T, Fang J, Ding Y, Qin Z, Song H, Hu H, Zhao H, Mo Q, Zhou J, Wu J, Liu X, Wang W, Pang R, Chen H, Wang X, Liu Z. Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial. Ann Intern Med. 2021 Oct;174(10):1357-1366. doi: 10.7326/M21-1814. Epub 2021 Aug 17. PMID 34399062
• Results publication: Zhu L, Sun Y, Yan S, Liu X, Wang X, Liu Z. Efficacy of acupuncture on drinkers with chronic prostatitis / chronic pelvic pain syndrome: secondary analysis of a randomized clinical trial. Acupunct Med. 2024 Oct;42(5):243-250. doi: 10.1177/09645284241274158. Epub 2024 Sep 1. PMID 39219163
• Results publication: Zhu L, Fang J, Sun Y, Yang M, Yao H, Liu Z. Impact of ejaculation upon effect of acupuncture on chronic prostatitis/chronic pelvic pain syndrome: Secondary analysis of a randomized controlled trial. Integr Med Res. 2023 Jun;12(2):100943. doi: 10.1016/j.imr.2023.100943. Epub 2023 Apr 3. PMID 37122487

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form (PDF, 2017-09-04)

• Zhishun Liu, Principal investigator, Guang'anmen Hospital of China Academy of Chinese Medical Sciences