STRENGTHS AND LIMITATIONS OF THIS STUDY

Research with musculoskeletal focus has shown positive results for men with chronic primary pelvic pain syndrome but has not yet been evaluated with objective urodynamic measurements, including the assessment of the pelvic floor muscles.

This study will explore if subjective outcomes can be correlated to objective changes on urodynamic measures, which has not been addressed in earlier research.

This study will have a follow-up period of 12 months, which is longer than that in previous studies and relevant for a patient group with long-term symptoms.

Due to repeated urodynamic testing, recruitment to the study may be challenging.

Introduction

Chronic primary pelvic pain syndrome (CPPPS) is a condition of persisting pain in the pelvic and pelvic floor area that effect both men and women. It is often associated with negative cognitive, behavioural, sexual and emotional consequences as well as with symptoms suggestive of lower urinary tract, sexual, bowel, pelvic floor or gynaecological dysfunction.1 CPPPS gathers different patient groups such as bladder pain syndrome, vulvodynia, chronic proctalgia and chronic prostatitis (CP). CP has over time been believed to be related to inflammation, usually secondary to infection. However, in over 90% of patients presenting with symptoms of prostatitis, there is no genuine infection or inflammation to be found.2 The European Association of Urology, EAU, thereby advocates the use of the term male CPPPS rather than CP.1

The aetiology and pathophysiology of male CPPPS is still unclear and is a diagnosis of exclusion that comes into question when there is no proven infection or other obvious local pathologies that may account for the pain. Diagnosing male CPPPS is complicated because of the patient’s variety of symptoms and these patients are often misunderstood, recurrently misdiagnosed and many men suffer for years before getting the diagnosis.1 3 4 The prevalence of prostatitis symptoms ranges from 1 to 14,2% (1), but the process of collecting data vary between studies.

The main symptom of male CPPPS is pain, which may be located in the perineum, outer genitalia, around the anus, lower abdomen or radiating back to the seat and lower back.1 5 In addition to the pain, patients often present with lower urinary tract symptoms (LUTS), such as hesitancy, urge, dysuria and incontinence.1 6 7 Within the group of male CPPPS it is also common with symptoms such as intestinal and sexual dysfunction, as well as adverse effects on quality of life (QoL).5 8

Pelvic floor myalgia has since long been suggested as a possible cause of pain in men with CPPPS, and pelvic floor dysfunction is frequently found in patients with chronic pelvic pain conditions.8–11 Functional testing of the pelvic floor and lower urinary tract using urodynamic (UD) testing has been studied,6 but most studies have not performed a complete UD testing with a urethral pressure profile or electromyography (EMG).

Both diagnosing and treating men with CPPPS are challenging. Evidence has been put forward in favour of a multi-modal holistic treatment approach.12 13 Biofeedback for pelvic floor re-education and relaxation has shown a reduction of pain and improvement of LUTS and QoL in these patients but has mainly been assessed with short follow-up.14 15 Furthermore, the assessment has been based on subjective measurements rather than on objective.

The aim of this study is to elucidate whether pelvic floor re-education using biofeedback and home training will give a long-lasting improvement in symptoms, assessed with the National Institute of Health–Chronic Prostatitis Symptom Index (NIH-CPSI)5 and to explore if outcomes can be correlated to changes in objective urodynamic measures and pelvic floor evaluation.

Methods and analysisPatient selection

Men with the diagnosis of CPPPS referred to our clinic who meet the inclusion, but not the exclusion criteria, and living in or around Stockholm County will be recruited for the study. We will also contact urology and andrology clinics within the region that meet patients with CPPPS who could be interested in participating for their referral.

Inclusion criteria

Men aged over 18, residents in Sweden, diagnosed with CPPPS according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10) (N41.1 (chronic prostatitis), N41.9 (Inflammatory disease of the prostate, unspecified), N50.8F (Chronic Pelvic Pain Syndrome in men).

Exclusion criteria

Cancer in the abdomen or pelvic organs (current or previous).

Congenital anomalies affecting the pelvic region (bladder exstrophy, myelomeningocele, etc).

Transsexual male, (ie, at birth biologically female).

Diseases affecting the nerve function to the pelvic and/or lower extremities, other diseases or ongoing treatment that could have an impact on the outcome of the study.

Incapability to participate in testing or follow training instructions due to mental incapacity, language difficulties, etc.

Study design

This study will be performed as a randomised controlled single-blinded clinical study with a study period of 12 months from inclusion until completion. After obtaining written consent (online supplemental file 1), the participants will be enrolled and baseline measurements conducted (NIH-CPSI, urodynamic evaluation and pelvic floor muscle assessment). The study participants are then randomly assigned in a 1:1 ratio either to intervention or control group.

Intervention

The intervention consists of a short daily session of pelvic floor muscle training, performed at home for 6 months. To facilitate and guide the home training, this is combined with four bio-feedback sessions during the first 2 months. The study participants will receive individual instruction based on the pelvic floor assessment from the baseline visit.

After embarking on home training, the participants will attend four biofeedback sessions once every other week to guide and facilitate the training. The aim is to teach the participants adequately how to contract and relax their pelvic floor muscles. Each biofeedback session will take 45 min. Every session starts with attaching two small EMG surface electrodes to the skin surface on either side of the anus as well as a grounding electrode to one of the iliac crests. During this, the participant needs to be undressed on the lower body but can put on their underwear or have a towel over them during the actual training. With the electrodes in place, it is possible to record the electrical activity of the pelvic floor muscles with the urodynamic device (Laborie Nexam Pro Urodynamics System). The muscle activity is simultaneously visualised on a computer screen in front of the participant. This enables him to receive biofeedback on his attempts to contract and relax his pelvic floor muscles. For specifications concerning the EMG system, see table 1.

Table 1

Electromyography system specifications

The pelvic floor training, both home training and biofeedback sessions, will initially aim at gaining neuromuscular control so that the participants can steer their pelvic floor muscles to contract and relax correctly with a primary focus on the ability to relax. Thereafter the training gradually will be increased in difficulty level including maximum contractions, still maintaining the capability to fully relax between contractions, as well as going from training laying down to more upright and dynamic positions.

The participants will be instructed to perform their home training programmes daily for 6 months, taking approximately 10 min. Once weekly the participants will report their training in a digital diary. The home training will be followed up at the four clinical visits for biofeedback training and thereafter by phone every 5 weeks. At the follow-up the training will be assessed and adjusted according to the principles above. All training from startup throughout 6 months will be guided and followed up by a specialised physiotherapist (HHG).

A reevaluation will be done at 3, 6 and 12 months. At 6 and 12 months repeating the baseline tests. At 3 months a renewed assessment of muscle function and the NIH-CPSI questionnaire will be performed.

The control group will be instructed not to engage in any new treatment for their CPPPS during the study period. If they have ongoing treatment at inclusion, medication, for example, they are instructed to continue with this in an unchanged manner during the study. After the 6 month evaluation, all participants in the control group will be offered to be enrolled in the treatment group, with the same set-up and follow-up as the treatment group.

Measurements

The NIH-CPSI questionnaire5 is a validated nine-item problem and symptom questionnaire developed for men with CPPPS available in Swedish. The questions are categorised into three domains: pain, urology symptoms and quality of life impact. The result is calculated as a total score as well as sub-score for each domain.

Urodynamic evaluation will be conducted according to the International Continence Society Good Urodynamic Practice.16 The investigation will include measurement of EMG as well as urethra pressure point profiles.

The muscle function will be assessed concerning resting tone, voluntary contraction, ability to relax after contraction, tenderness/pain according to Frawley et al17 and power on a modified Oxford scale.18 All assessments will be done by a specialised physiotherapist (HHG).

NIH-CPSI and pelvic floor assessment will be conducted at baseline, 3, 6 and 12 months. Urodynamics will be performed at baseline, 6 and 12 months. For measurement time points see figure 1.

Sample size calculation

The power was calculated as the percentage of trials with two-sided p value of <0.05 using analysis of covariance (ANCOVA) based on 500 simulations for each combination of a range of assumed SDs (4.5 (0.5) 8), differences of total NIH-CPSI scores (−4 (0.5) –6) and the correlations (ρ) between response outcomes (−1 (0.1) 1).

At a significance level 0.05 and a power of 0.80, the sample size calculated based on a clinically meaningful difference of total scores of NIH-CPSI of six (19), was 16 in each group. Due to possible dropouts (n=4), we aim to include 20 participants in each arm.

Outcomes

The primary outcome is the difference in total score reduction of the NIH-CPSI questionnaire from baseline to 6 months post-treatment. This will answer our primary research question, whether biofeedback training in combination with home training of the pelvic floor muscles provides significant symptom relief compared with traditional treatment without myofascial focus. A six-point decline in the total score is considered clinically relevant based on previous studies.19

The secondary outcome is the difference in sub-score reduction according to the domains: pain, urology symptoms and quality of life impact on the NIH-CPSI questionnaire from baseline to 6 months post-treatment. Secondary outcomes are further selected to explore if subjective measurements on the NIH-CPSI can be correlated to pelvic floor muscle measurements and numerical results from the UD testing. Secondary outcome is also the long-term effect of the treatment at 12 months.

Statistical analysis

We will use ANCOVA adjusted for the baseline total NIH-CPSI to evaluate the effects of pelvic floor re-education and home training on total NIH-CPSI score at 6 months. We will obtain point and interval estimates of the intervention effect and test the null hypothesis that the effect of intervention is zero. The same approach will be used to explore the effect of pelvic floor re-education and home training on the secondary outcome variables. These analyses will be performed using an intention-to-treat approach. In per-protocol analyses, we will compare the effect for individuals with low and high compliance to the intervention.

The analysis to evaluate agreement between objective measurements (from the UD testing and pelvic floor muscle assessment) and subjective outcome variables (NIH-CPSI) will be performed using models for both continuous variables and categorical variables.

Patient and public involvement

The study design has originated from our extensive knowledge of this patient group and has been discussed in our research group, in particular, to take the patients’ perspective into account. In a second step we invited patients with diagnosis of CPPPS to comment on the study design including giving their general reflections concerning research aspects from their point of view. This strengthened our intervention plan as well as confirmed the challenges of recruitment to conduct repeat urodynamic evaluations as well as the challenges concerning compliance to daily training, aspects that we have considered and have attempted to address.

Ethics and dissemination

There is little research done concerning men with CPPPS. Studies emphasise that commonly used treatment methods are not particularly effective and that men often have difficulty finding effective treatment.1 13 Research with a musculoskeletal focus for this patient group has shown positive results, but follow-up periods are commonly relatively short 3 to 6 months. Men with CPPPS suffer greatly from their ailments, many times for years; therefore, further research is needed to increase the understanding of how musculoskeletal treatment can provide symptom relief and whether the treatment of that kind can have an effect over a longer period.3 By performing a randomised controlled trial (RCT) of high scientific quality, our intention is to clarify this.

Like all studies involving human participants, RCTs raise many different ethical issues, ranging from obtaining informed consent to minimising risks and protecting privacy and confidentiality. One of the most important issues raised by an RCT is whether it is ethical to withhold a possibly effective intervention from research participants to satisfy scientific objectives. Withholding interventions from research participants can be ethical, provided it does not lead to deterioration of their medical condition. In our RCT all participants will have the possibility to get the treatment, although the control group will have to wait 6 months on the standard care before receiving the treatment.

Earlier studies have evaluated subjective outcomes using the NIH-CPSI questionnaire but without combining results with more objective outcome. One of the strengths of this study is our intent to explore if subjective outcomes can be correlated to changes in objective urodynamic measures and pelvic floor muscle evaluation. This can give us valuable insights in the mechanism of CPPPS as well as the benefit of biofeedback treatment of the pelvic floor muscles, for this patient group. UD testing includes catheterisation, which can give rise to some discomfort, a small risk of bleeding from the urethra as well as a small risk for urinary tract infection. Studies concerning patient experiences of UD testing show that the tolerance and acceptance of this type of examination are generally good and that many patients (> 50%) do not experience any discomfort at all in connection with it.20

The intervention group will carry out daily home training and come to the clinic for biofeedback sessions. This will be time consuming but has few side effects. For those who train intensively to activate and tense a muscle/muscle group, discomfort such as soreness or pain may occur locally. The risk of this can be considered very small as the main focus in this study will be on training muscular relaxation. The ongoing guidance during the training period aims also to support the participants so that the training is performed as intended and with an appropriately dosed force.

The study result will be published in a peer-reviewed medical journal and presented at national and international conferences.

Ethics statementsPatient consent for publication

Not applicable.