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Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for the Treatment of Urological Chronic Pelvic Pain Syndromes
Abstract
Purpose:
We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes.
Materials and Methods:
We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods.
Results:
There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03).
Conclusions:
We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.
The urological chronic pelvic pain syndromes, which include interstitial cystitis/painful bladder syndrome in men and women, and chronic prostatitis/chronic pelvic pain syndrome in men, are characterized by pelvic pain with concurrent urinary symptoms. PBS, as defined by the International Continence Society, is “the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms, such as increased daytime and nighttime frequency, in the absence of proven urinary infection or other obvious pathology.”1 These symptoms may be related to interstitial cystitis, with additional characteristic findings of glomerulations and/or ulcers present at cystoscopy, and hydrodistention.2 The underlying pathophysiology of these disorders has not been elucidated, and the relationship between PBS and IC is not clear.
Chronic prostatitis/chronic pelvic pain syndrome or NIH type IIIA/IIIB prostatitis is also characterized by pelvic pain and lower urinary tract symptoms in the absence of proven urinary tract infection or other obvious disease pathology. CP/CPPS is also a clinical description based on symptoms and does not depend on urodynamic or cystoscopic findings.
Estimates of the national prevalence of these UCPPS vary widely according to the populations studied and the survey methodology. In 1990 interstitial cystitis was thought to affect as many as 500,000 United States citizens with 25% of patients younger than 25 years.3 Recent estimates vary between 0.2% and 3.4% of the population.4–9 In 2000 annual national expenditures in the United States for IC/PBS were estimated at $797 million.10 Estimates of the prevalence of symptoms characteristic of CP/CPPS vary similarly and may be higher, with community based surveys demonstrating a prevalence of 8% to 11.5% in men younger than 50 years.11,12
On examination, tension and tenderness of the pelvic floor musculature and other somatic tissues are commonly present in patients with UCPPS.13–20 It is thought that these myofascial abnormalities contribute significantly to the pain of UCPPS. However, it is not known whether these musculoskeletal abnormalities are a consequence of lower urinary tract symptoms or are a primary disorder which gives rise to secondary urinary symptoms. Frequently found abnormalities include myofascial trigger points defined as taut bands or tender nodules that evoke twitch responses or reproduce the character and location of symptoms during careful palpation.21 Importantly there have been several reports of UCPPS symptom relief by therapeutic efforts directed at those muscular abnormalities.16–20 In practice those therapeutic interventions are typically performed by a physical therapist skilled in manual therapy techniques. Although widely practiced, to our knowledge no randomized trials have established the effectiveness of specialized external and pelvic floor physical therapy for UCPPS.
Since there have been few prospective randomized clinical trials involving physical therapies to guide us, we designed a study to determine whether a randomized study of physical therapy for treatment of UCPPS is feasible. The criteria to assess feasibility were whether patients with UCPPS are willing to be randomized between 2 forms of manual physical therapy, whether physicians are capable of identifying relevant myofascial abnormalities during evaluation of patients with UCPPS, whether we can assure that the manual therapy treatments are similar in nature and quality at several study sites, and whether we can assess the safety of manual therapies for UCPPS and determine the response rate to manual physical therapy.
METHODS
The Urological Pelvic Pain Collaborative Research Network is a cooperative network of investigators from 20 clinical centers and a Data Coordinating Center funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (http://www.cceb.med.upenn.edu/uppcrn) (Appendix 1). The study received institutional review board approval at all enrolling sites and the Data Coordinating Center located at the University of Pennsylvania School of Medicine. The UPPCRN Data and Safety Monitoring Board oversaw aspects of clinical trial design, conduct and analyses of trial data.
Study Design
This was a randomized, single-blind clinical trial in which 8 participants each were to be recruited by a subset of 6 of the UPPCRN clinical centers for a total sample size of 48. Subjects who met eligibility criteria and did not have any of the exclusion factors were randomized in equal number to MPT or GTM and were not informed whether the treatment they were receiving was MPT or GTM (Appendix 2). MPT treatment targeted internal (pelvic) and external trigger point work, focusing on the muscles and connective tissues of the pelvic floor, hip girdle and abdomen, whereas GTM was considered a nonspecific somatic treatment with full-body Western massage and was included as a comparison treatment arm. Patients were scheduled for 10 weekly treatments of 1 hour each. Participation ended when a subject completed treatment and outcome assessment, voluntarily withdrew or was withdrawn by their physician for medical reasons.
Study Measures
Since this was a pilot study to establish the feasibility of comparing 2 manual therapies, many of the trial outcomes were related to study conduct. These measures included 1) the proportion of patients who consented to join the study from among all eligible patients approached, 2) the number of patients deemed eligible by physicians based on history and clinical examination, and the number considered ineligible by physical therapists due to lack of relevant physical abnormalities, and 3) adherence of therapist to prescribed therapeutic protocol as determined by records of treatment.
The primary measures related to patient outcomes including safety and efficacy were 1) adverse events including serious adverse events, 2) patient global response assessment with patients classified as responders if they stated that symptoms were moderately or markedly improved compared to how they were before treatment (Appendix 3) and 3) change in several validated symptom scales.
Eligibility Assessment
Recruitment was conducted from among patients who attended urology and urogynecology clinics at each of the designated clinical sites based on the inclusion and exclusion criteria outlined in Appendix 2. Potential participants had to be adult and have a clinical diagnosis of IC/PBS or CP/CPPS. Based on personal experience the investigators hypothesized that the time to response to physical therapies is proportional to the duration of symptoms. Since treatment was limited to 10 sessions in this protocol we restricted entry to subjects with symptoms present for less than 3 years. The patient must have previously undergone at least 1 course of another form of therapy for his/her symptoms. We also excluded patients who were intolerant to digital vaginal or rectal examination, ie unable to tolerate the MPT treatments. Participants who had previously undergone myofascial physical therapy for symptoms were also ineligible.
Certification of Treating Therapists
Certification of treating therapists took place in several steps. Up to 2 physical therapists were involved at each clinical site. As a prerequisite the licensed physical therapists and collaborating investigator physicians attested that they already routinely treated patients with UCPPS using MPT techniques similar to those used in the study. To standardize MPT and GTM treatments therapists received study materials including the study protocol, description of the MPT and GTM treatments, and DVDs demonstrating MPT and GTM therapies. They attended a weekend certification session during which the study protocol and treatments were reviewed and demonstrated on volunteers. A licensed massage therapist (RH-P) instructed therapists in the proper performance of a traditional Western style massage.22 For preliminary certification candidate therapists demonstrated full understanding and competence in the execution of the steps involved in completion of MPT and GTM treatments. After subsequently completing and attesting to correct performance of 5 treatments of each type, therapists were then certified to participate in the protocol.
Preintervention Assessments
Clinically identified potential participants were counseled about study procedures and were administered informed consent. During the first study visit patients completed symptom scales including a rating of average pelvic/bladder discomfort or pain, and of urinary urgency and urinary frequency severity, all rated on average in the last 4 weeks. Other symptom scales included the IC Symptom and Problem Index,23 NIH-CPSI (males),24 SF-12 Health Status Questionnaire25 and a gender specific sexual function index (FSFI26 or Sexual Health Inventory for Men27). Patients also underwent pelvic examination by the study physician including transvaginal or transrectal examination of the soft tissues of the pelvic floor (levator ani, obturator internus and tissues of the urogenital diaphragm). Patients were eligible to continue with study participation if some pelvic floor tenderness was elicited in any of the designated areas during this baseline pelvic examination. Patients without such tenderness were excluded from further participation.
At the second study visit patients underwent a more complete examination of the musculoskeletal system and soft tissues by the study physical therapist. Patients were eligible to continue participation in the study only if the therapist confirmed that there was tenderness present on pelvic examination. The location of the tenderness did not have to correspond to that found by the primary investigator. Other pretreatment assessments by the physical therapist included mapping of any scars and connective tissue restrictions, and evaluation of all soft tissues of the back, hip girdle, abdominal wall and pelvic floor.
Participants meeting all eligibility criteria were randomly assigned in equal proportions within each of the 6 strata defined by clinical site via a prespecified sequence distributed in a series of sealed envelopes to receive MPT or GTM. Each participant underwent 10 weekly 1-hour treatments by the physical therapist. Patients were contacted by telephone by the study coordinator every week between treatments and asked about any adverse events. Study coordinators remained masked to study treatment assignment.
MPT Treatment
Patients randomized to the MPT group underwent connective tissue manipulation to all body wall tissues of the abdominal wall, back, buttocks and thighs that clinically were found to contain connective tissue abnormalities and/or myofascial trigger point release to painful myofascial trigger points. CTM was applied bilaterally to the patient in the prone position, posteriorly from inferior thoracic level 10 to the popliteal crease. This was done until a texture change was noted in the treated tissue layer. Manual techniques such as trigger point barrier release with or without active contraction or reciprocal inhibition, manual stretching of the trigger point region and myofascial release were used on the identified trigger points.
Once adequate changes were noted in the posterior tissues the patient was repositioned into the supine position for CTM to bilateral anterior tissues. This allowed the inclusion of the thighs, laterally, anteriorly and medially from the knee up to and including the thigh crease. CTM was performed on the abdominal wall from the suprapubic rim to the anterior costal cartilages, with a concentration of manual interventions to focus on the periumbilical tissues. Manual trigger point release techniques were used to treat any noted trigger points or scars in the anterior or posterior lower quadrants. It was presumed that external episiotomy scars found in the perineum or external pelvic floor were especially relevant.
Transvaginal/transrectal treatment of the soft tissues of the pelvic floor with CTM of periurethral tissues, arcus tendineus fascia pelvis, muscle origins and insertions was also performed. Myofascial manipulation to each muscle group was performed with the focus on restrictive bands and trigger points. Neuromuscular reeducation, focusing on lengthening the pelvic floor musculature, was performed in conjunction with myofascial manipulation including post-isometric relaxation.
During the time between visits, when deemed appropriate by the therapist, patients were asked to double void 2 to 3 times after each void (ie after voiding, to remain seated on the toilet and to relax or drop the pelvic floor again as if to initiate voiding). This was meant to facilitate a proprioceptive awareness of the movement of the pelvic floor during voiding, hoping to use recent recall to make dropping the pelvic floor easier. As their ability to drop the pelvic floor improved the patients could add 5 pelvic drops to the end of the exercise. Squatting was also taught as a position to use to facilitate and practice pelvic floor drops.
The treating physical therapist was permitted to vary the exact content of the hour-long MPT treatment based on the physical abnormalities present and on the response of tissues to manipulation. Initial treatments devoted at least half of the treatment time to external myofascial therapy. As connective tissue changes became evident with repetitive treatments, less time was typically needed for treatment of external tissues and more time was devoted to internal (transvaginal, transrectal) work. When the severity of symptoms prohibited transvaginal/transrectal myofascial trigger point release or CTM (although initial examination and inclusion of the patient was possible) this variance was allowed.
To maximize the potential for a treatment effect each therapist typically offered appropriate home exercises to each patient randomized to the MPT arm. Each therapist was provided with a catalog of stretches and/or exercises specifically chosen for this study and the appropriate exercise/stretch was given to the patient when desired by the therapist. Importantly these were not Kegel exercises which can increase the irritability of myofascial trigger points and exacerbate symptoms if practiced during an early phase of therapy. Later after muscle control is achieved a focus on improving muscle strength may be more appropriate and was permitted by the protocol.
GTM Treatment
Patients randomized to the GTM group received weekly massages consisting of full body Western massage for 1 hour. Unlike the MPT arm in which the therapists tailored the focus of therapy to target individual patient needs, GTM was used according to a common study protocol. This differs from clinically practiced therapeutic massage as the participating therapists were neither permitted to deviate from the GTM regimen nor to tailor the massage techniques to individual patients. Techniques used include effleurage, petrissage, friction, tapotement, vibration and kneading. These techniques were applied in upper and lower limbs, trunk, buttocks, abdomen, head and neck each for prescribed time periods (eg 10 minutes massage to head and neck). Patients randomized to GTM were not provided with a home exercise program. The GTM treatment was not similar to the MPT treatment with respect to the manual methods administered to the body tissues, ie there was no methodological overlap between treatments.
Statistical Analysis
To ensure balance across treatment arms a stratified randomization was used. Within each of the 6 strata defined by clinical site subjects were further stratified by gender and randomly allocated in equal proportions to the 2 treatment arms.
Although this was a pilot study for which comparison of treatment efficacy was a secondary outcome, the small number of participants (24 per arm) was adequate to provide approximately 80% power to detect a 40% absolute difference (eg 70% vs 30%) in response rates between MPT and GTM using a 2-sided test at the 5% level. With a total of 24 subjects per treatment arm 95% confidence intervals for rates (such as response and adverse events) have a maximum width of ±20%, ignoring slight adjustments for variability due to clinical site.
An intent to treat analysis including all randomized participants was implemented. Participants who discontinued treatment during the trial, particularly in the case of an adverse event, were not considered withdrawals from study unless they withdrew consent for further followup. However, randomized participants who withdrew before the final assessment at 12 weeks were considered to represent treatment failures and were included in the denominator for evaluation of response rates based on the GRA.
The primary efficacy end point was response rate based on the GRA (Appendix 3). An analysis comparing response rates between treatment arms using the exact conditional test version of Mantel-Haenszel methods to adjust for within-center clustering was implemented within the Proc-StatXact software system.28 Outcome measures between treatment arms were analyzed with Wilcoxon rank sum tests, and outcome scores within treatment groups and disease states were determined with paired t tests. Statistical significance was at p <0.05.
RESULTS
As detailed in the figure 369 patients with UCPPS were reviewed for study participation, of whom 68 (18%) agreed to participate and 47 were randomized, including 23 (49%) men and 24 (51%) women. Recruitment took place during 6 months. All except 1 patient identified as eligible by the study physician were also considered eligible by the study physical therapist on the basis of the presence of tenderness of the pelvic floor. There were 24 (51%) patients randomized to GTM and 23 (49%) to MPT. Patients with IC/PBS included 24 women and 2 men, and 21 men had a CP/CPPS diagnosis. A total of 44 (94%) patients completed the study, with 2 withdrawing from the GTM treatment arm and 1 withdrawing from MPT.
The baseline demographic characteristics of study participants overall and by treatment assignment are presented in table 1. Mean age was 43 years (range 22 to 76) and 41 participants (87%) were white. Patient self-reports of medical history differed between the 2 disorders with a higher incidence of migraine headaches, GI disorders, drug allergies and sinusitis in those with IC/PBS (p <0.05). Patient symptoms before treatment were rated moderate to severe (range 4 to 10 on a scale of 10) for pain in 96%, urgency in 91% and frequency in 89% of participants (table 2).
Table 1.
Summary of demographic characteristics
| Treatment | ||||
|---|---|---|---|---|
| GTM | MPT | Overall | p Value | |
| No. subjects | 24 | 23 | 47 | |
| No. gender (%): | 0.66 | |||
| M | 11 (46) | 12 (52) | 23 (49) | |
| F | 13 (54) | 11 (48) | 24 (51) | |
| Age: | 0.28 | |||
| Mean ± SD | 44.9 ± 14.0 | 41.1 ± 11.4 | 43.0 ± 12.8 | |
| Median (range) | 45.1 (22–76) | 40.9 (23–66) | 43.3 (22–76) | |
| No. ethnicity/race (%): | 0.42 (white vs nonwhite) | |||
| North American Indian/North Native | 0 | 0 | 0 | |
| Asian/Asian-American | 0 | 1 (4) | 1 (2) | |
| Black/African-American | 0 | 2 (8) | 2 (4) | |
| White/caucasian | 22 (92) | 19 (83) | 41 (87) | |
| Native Hawaiian/other Pacific Islander | 0 | 0 | 0 | |
| Other | 2 (8) | 1 (4) | 3 (6) | |
| No. diagnosis (%): | 0.67 | |||
| IC/PBS | 14 (58) | 12 (52) | 26 (55) | |
| CP/CPPS | 10 (42) | 11 (48) | 21 (45) | |
| No. educational level (%): | 0.13 | |||
| Less than high school | 0 | 0 | 0 | |
| High school/GED | 5 (21) | 1 (5) | 6 (13) | |
| Some college | 7 (29) | 7 (30) | 14 (30) | |
| Graduated college or greater | 12 (50) | 15 (65) | 27 (57) | |
| No. employment (%): | 0.15 | |||
| Employed | 14 (58) | 17 (74) | 31 (66) | |
| Unemployed/retired | 7 (29) | 2 (9) | 9 (19) | |
| Full-time homemaker | 3 (13) | 2 (9) | 5 (11) | |
| Disabled | 0 (0) | 2 (9) | 2 (4) | |
| No. annual family income (%): | 0.89 | |||
| Less than $10,000 | 1 (7) | 1 (7) | 2 (7) | |
| $10,001–$25,000 | 1 (7) | 0 (0) | 1 (3) | |
| $25,001–$50,000 | 3 (20) | 4 (29) | 7 (24) | |
| $50,001–$100,000 | 4 (27) | 3 (21) | 7 (24) | |
| Greater than $100,000 | 6 (40) | 6 (43) | 12 (41) | |
| Missing | 9 | 9 | 18 | |
Treatment groups were similar with respect to all demographic characteristics at baseline. All but 2 patients in the IC/PBS group were female.
Table 2.
Baseline symptom characteristics by treatment group at baseline
| No. GTM (%) | No. MPT (%) | No. Total (%) | p Value* | |
|---|---|---|---|---|
| Av pain severity score: | 0.17 | |||
| None (0) | 0 (0) | 0 (0) | 0 (0) | |
| Mild (1–3) | 2 (8) | 0 (0) | 2 (4) | |
| Moderate (4–6) | 11 (46) | 9 (39) | 20 (43) | |
| Severe (7–10) | 11 (46) | 14 (61) | 25 (53) | |
| Av urgency severity score: | 0.15 | |||
| None (0) | 0 (0) | 0 (0) | 0 (0) | |
| Mild (1–3) | 4 (17) | 0 (0) | 4 (9) | |
| Moderate (4–6) | 8 (33) | 9 (39) | 17 (36) | |
| Severe (7–10) | 12 (50) | 14 (61) | 26 (55) | |
| Av frequency severity score: | 0.16 | |||
| None (0) | 0 (0) | 0 (0) | 0 (0) | |
| Mild (1–3) | 4 (17) | 1 (4) | 5 (11) | |
| Moderate (4–6) | 6 (25) | 5 (22) | 11 (23) | |
| Severe (7–10) | 14 (58) | 17 (74) | 31 (66) |
Pain, urgency and frequency values represent means of scores at baseline visits 1 and 2. Treatment groups were similar at baseline with respect to symptom severity.
The median (range) number of treatment visits administered in the MPT group was 10 (4 to 10) and in the GTM group was 10 (1 to 10). Of the patients 87% in each arm received at least 7 of the assigned treatments. Therapist adherence to the treatment protocols was excellent. During GTM treatments therapists recorded having performed massage to all body parts during all treatments as prescribed by the protocol except for omission of head and neck and/or abdominal massage during most treatments in 1 patient (protocol violation). Therapists reported they applied all of the allowed therapeutic interventions at least some of the time and varied treatments as allowed by the protocol. The most commonly used interventions were connective tissue manipulation of external tissues of lower limbs, buttocks, abdominal wall and pelvic floor as well as trigger point treatments to the abdominal wall and pelvic floor. Individualized home stretch/exercise programs were prescribed for 21 (48%) patients, of which 1 patient performed none, 5 performed some and 15 performed all. After treatment 42 of 44 (95%) patients correctly identified the study group to which they were assigned.
Adverse events were reported by 5 (21%) patients in the GTM group and 12 (52%) patients in the MPT group (table 3). Pain was the most common class of AEs as reported by 14 (30%) participants, of which 3 pain AEs were rated as severe (1 in GTM group and 2 in MPT group).
Table 3.
Cumulative adverse events by body system and treatment arm
| No. GTM Toxicity Grade | No. MPT Toxicity Grade | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| None (grade 0) | Mild (grade 1) | Moderate (grade 2) | Severe (grade 3) | Total (%) | None (grade 0) | Mild (grade 1) | Moderate (grade 2) | Severe (grade 3) | Total (%) | |
| Highest AE grade | 19 | 3 | 1 | 1 | 5 (21) | 11 | 8 | 2 | 2 | 12 (52) |
| Cardiovascular (arrhythmia) | 24 | 0 | 0 | 0 | 0 | 22 | 0 | 1 | 0 | 1 (4) |
| Constitutional symptoms | 22 | 2 | 0 | 0 | 2 (8) | 22 | 1 | 0 | 0 | 1 (4) |
| Hemorrhage | 24 | 0 | 0 | 0 | 0 | 22 | 1 | 0 | 0 | 1 (4) |
| Infection | 23 | 0 | 1 | 0 | 1 (4) | 23 | 0 | 0 | 0 | |
| Musculoskeletal | 24 | 0 | 0 | 0 | 0 | 22 | 1 | 0 | 0 | 1 (4) |
| Pain (unspecified): | 21 | 1 | 1 | 1 | 3 (13) | 12 | 1 | 2 | 11 (48) | |
| Abdomen/intestine | 1 | 1 | 0 | |||||||
| Back | 0 | 1 | 0 | 1 | 0 | 0 | ||||
| Bladder/rectum/pelvis/genital | 1 | 2 | 1 | 5 | 1 | 2 | ||||
| Genitourinary | 23 | 1 | 0 | 0 | 1 (4) | 19 | 4 | 0 | 0 | 4 (17) |
Body systems were not included if no related AEs were reported. All adverse events included, regardless of relationship to study intervention. Patients were counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than 1 body system category. An adverse event was not counted if the same event was observed at baseline with an equal or greater toxicity grade.
The overall GRA response rates and rates for subgroups of subjects with IC/PBS and CP/CPPS are shown in table 4. The overall GRA response rate of 57% in the MPT group was significantly higher than the rate of 21% in the GTM treatment group (p = 0.03). As detailed in table 4 a significant difference between treatment arms was present in the IC/PBS group but not in the CP/CPPS group since many patients with CP/CPPS responded to GTM and MPT.
Table 4.
Global response assessment by treatment group
| No. GTM | MPT | Total | p Value | |
|---|---|---|---|---|
| No. response rate based on GRA (%):* | 0.03 | |||
| Responders | 5 (21) | 13 (57) | 18 (38) | |
| Nonresponders | 19 (79) | 10 (43) | 29 (62) | |
| No. response rate for IC/PBS subgroup (26) (%): | 0.03 | |||
| Responders | 1 (7) | 6 (50) | 7 (27) | |
| Nonresponders | 13 (93) | 6 (50) | 19 (73) | |
| No. response rate for CP/CPPS subgroup (21) (%): | 0.39 | |||
| Responders | 4 (40) | 7 (64) | 11 (52) | |
| Nonresponders | 6 (60) | 4 (36) | 10 (48) | |
| No. global assessment of response: | ||||
| Markedly improved | 3 | 8 | 11 | |
| Moderately improved | 2 | 5 | 7 | |
| Slightly improved | 10 | 6 | 16 | |
| No change | 5 | 2 | 7 | |
| Slightly worsened | 1 | 0 | 1 | |
| Moderately worsened | 1 | 1 | 2 | |
| Markedly worsened | 0 | 0 | 0 | |
| Missing or withdrawn | 2 | 1 | 3 | |
Tables 5 and and66 show baseline and 12-week symptom scores according to clinical diagnosis of IC/PBS and CP/CPPS, respectively, stratified by treatment assignment. MPT resulted in improved (decreased) symptom scores for patients with IC/PBS and CP/CPPS (table 5, p <0.05). GTM did not provide any significant relief of symptom scores for the IC/PBS group, but was associated with improvements in the CP/CPPS group in domains of pain, quality of life and ICSI (table 6, p <0.05). The SF-12 physical and mental component scores in both disorder groups were unaffected by GTM. Sexual function improved with MPT for the IC/PBS group, but not CP/CPPS.
Table 5.
Comparison within and between treatment groups of baseline and end point symptom scores of patients with IC/PBS
| Mean ± SD MPT | Mean ± SD GTM | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Baseline (12 pts) | 12 Wks (11 pts) | Mean Change (%) | p Value* | Baseline (14 pts) | 12 Wks (12 pts) | Mean Change (%) | p Value* | MPT vs GTM p Value† | |
| Pain (0–10) | 6.8 ± 2.0 | 4.2 ± 2.9 | −2.5 (−36.8) | 0.005 | 6.7 ± 1.6 | 5.9 ± 2.0 | −0.9 (−13.4) | 0.09 | 0.07 |
| Urinary urgency (0–10) | 6.8 ± 1.4 | 4.0 ± 2.7 | −2.7 (−39.7) | 0.01 | 6.7 ± 2.0 | 6.3 ± 2.5 | −0.8 (−11.9) | 0.26 | 0.14 |
| Urinary frequency (0–10) | 7.2 ± 1.4 | 3.5 ± 2.5 | −3.6 (−50.0) | 0.003 | 7.6 ± 1.7 | 6.8 ± 1.8 | −1.2 (−15.8) | 0.09 | 0.06 |
| ICSI | 13.0 ± 4.8 | 8.1 ± 4.9 | −4. 6 (−35 .4) | 0.02 | 12.8 ± 4.0 | 12.9 ± 4.7 | 0 (0) | 0.94 | 0.01 |
| ICPI | 12.1 ± 3.3 | 7.3 ± 4.7 | −4.7 (−38.8) | 0.006 | 11.5 ± 3.0 | 10.8 ± 4.0 | −1.3 (−11.3) | 0.09 | 0.04 |
| FSFI total‡ | 21.3 ± 7.1 | 25.3 ± 6.8 | 5.0 (23.5) | 0.002 | 18.4 ± 10.6 | 21.7 ± 8.8 | 1.4 (7.6) | 0.75 | 0.54 |
| SF-12 physical‡ | 40.8 ± 11.3 | 42.9 ± 13.2 | 1.3 (3.2) | 0.51 | 39.6 ± 10.0 | 38.2 ± 11.6 | −4.4 (−11.1) | 0.33 | 0.23 |
| SF-12 mental‡ | 33.5 ± 12.8 | 40.6 ± 9.1 | 6.2 (18.5) | 0.11 | 38.2 ± 12.1 | 39.2 ± 11.8 | 1.8 (4.7) | 0.50 | 0.44 |
Table 6.
Comparison within and between treatment groups of baseline and end point symptom scores of patients with CP/CPPS
| Mean ± SD MPT | Mean ± SD GTM | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Baseline (11 pts) | 12 Wks (11 pts) | Mean Change (%) | p Value* | Baseline (10 pts) | 12 Wks (9 pts) | Mean Change (%) | p Value* | MPT vs GTM p Value† | |
| NIH-CPSI Total (0–43) | 33.5 ± 4.3 | 19.2 ± 11.1 | −14.4 (−43.0) | 0.0003 | 25.8 ± 5.7 | 18.2 ± 9.6 | −6.8 (−26.4) | 0.03 | 0.07 |
| Pain (0–21) | 14.2 ± 2.5 | 8.0 ± 5.7 | −6.2 (−43.7) | 0.0007 | 12.7 ± 2.8 | 8.2 ± 5.6 | −4.4 (−34.6) | 0.03 | 0.39 |
| Urinary (0–10) | 8.9 ± 1.4 | 5.0 ± 2.8 | −3.9 (−43.8) | 0.0002 | 4.6 ± 2.7 | 3.9 ± 2.4 | −0.3 (−6.5) | 0.65 | 0.007 |
| Quality of life (0–12) | 10.4 ± 2.0 | 6.2 ± 3.8 | −4.2 (−40.4) | 0.002 | 8.5 ± 2.0 | 6.1 ± 3.2 | −2.1 (−24.7) | 0.05 | 0.10 |
| ICSI‡ | 11.3 ± 4.3 | 6.7 ± 4.8 | −5.3 (−46.9) | 0.004 | 5.6 ± 3.0 | 4.3 ± 2.7 | −2.3 (−41.1) | 0.02 | 0.09 |
| ICPI‡ | 10.4 ± 4.2 | 5.4 ± 5.0 | −5.9 (−56.7) | 0.008 | 3.8 ± 2.9 | 3.5 ± 3.0 | −1.3 (−34.2) | 0.48 | 0.11 |
| Sexual Health Inventory for Men | 18.8 ± 7.0 | 16.4 ± 9.7 | −2.5 (−13.3) | 0.26 | 17.1 ± 5.7 | 18.6 ± 6.6 | 2.2 (12.9) | 0.37 | 0.28 |
| SF-12 physical‡ | 40.4 ± 8.2 | 48.9 ± 10.0 | 6.1 (15.1) | 0.03 | 46.0 ± 9.0 | 50.2 ± 8.3 | 4.2 (9.1) | 0.08 | 0.73 |
| SF-12 mental‡ | 38.8 ± 10.7 | 43.7 ± 12.5 | 5.6 (14.4) | 0.10 | 37.2 ± 10.0 | 42.9 ± 9.8 | 5.8 (15.6) | 0.06 | 1.00 |
Physician baseline physical examination of internal muscle tenderness/pain to palpation across left and right side within each muscle group (total score for each muscle group range 0 to 6) resulted in an average total score of 10.96 across the 4 muscle groups, significantly less than the average assessment of 17.78 at baseline (p <0.001). Table 7 presents the level of tenderness/pain to palpation by disorder and treatment arm at baseline and at the final 12-week physician evaluation for each of the 4 muscle groups. MPT resulted in significant relief of tenderness/pain of the internal muscle groups in the patients with IC/PBS compared with GTM (p <0.05). The painful tender points in patients with CP/CPPS were relieved by MPT. However, some muscle groups (anterior and posterior levator) were similarly relieved after GTM. Minimal urogenital diaphragm tenderness did not change with either therapeutic approach.
Table 7.
Level of tenderness/pain to palpation across left and right side within muscle groups on pelvic floor examination
| Av IC/PBS | Av CP/CPPS | |||||
|---|---|---|---|---|---|---|
| Baseline | End Point | p Value* | Baseline | End Point | p Value* | |
| MPT (12 IC/PBS, 11 CP/CPPS): | ||||||
| Anterior levator | 3.67 | 2.00 | 0.02 | 3.72 | 1.64 | 0.003 |
| Posterior levator | 3.83 | 2.00 | 0.01 | 2.45 | 1.27 | 0.090 |
| Obturator internus | 3.17 | 1.73 | 0.01 | 2.36 | 0.55 | <0.001 |
| Urogenital diaphragm | 1.64 | 1.30 | 0.13 | 1.70 | 0.55 | 0.13 |
| GTM (14 IC/PBS, 10 CP/CPPS): | ||||||
| Anterior levator | 3.21 | 2.75 | 0.64 | 3.1 | 2.0 | 0.02 |
| Posterior levator | 3.29 | 2.42 | 0.12 | 2.9 | 0.78 | 0.001 |
| Obturator internus | 3.07 | 2.33 | 0.10 | 2.6 | 1.11 | 0.13 |
| Urogenital diaphragm | 2.07 | 1.42 | 0.33 | 1.4 | 0.22 | 0.08 |
DISCUSSION
To our knowledge this is the first published randomized trial comparing MPT and GTM for UCPPS treatment. We achieved our objective of demonstrating that such a clinical trial was feasible. Patients were willing to be randomized between 2 forms of manual treatment, with 38% (48 of 128) of those screened and found to be eligible for study inclusion agreeing to be randomized. We were also able to standardize both treatment approaches with reports of almost complete adherence to prescribed patterns for GTM and reports of appropriate, tailored myofascial physical therapy applied to patients in the MPT group. All AEs were more common in the MPT group as expected but our low study withdrawal rate and low rate of severe adverse events suggest that patients found the study treatments highly acceptable. Finally the overall response rate of 57% in the MPT group suggests that MPT represents a clinically meaningful treatment option, supporting the findings of others.16–20
A feasibility study was necessary as there was some skepticism regarding patient willingness to be randomized between 2 forms of manual therapy for UCPPS. Myofascial physical therapy can be painful and/or seem unduly invasive. In addition, UPPCRN sites are regional referral centers, and patients often expect immediate resolution of symptoms and may be unwilling to risk randomization to treatment with an unproven therapy. Study participation can be further challenged by the logistical obstacles of time and distance in such referral patients as this was a demanding treatment protocol that required multiple treatment visits.
We made several interesting observations. There was a striking difference in the response rate on the GTM arm between success rates in CP/CPPS (all men) and IC/PBS (all but 2 of whom were women) at 40% in CP/CPPS and 7% in IC/PBS. This suggests that CP/CPPS responds differently to GTM or that men respond differently to GTM, or that other un-measured factors are important. Since all the study therapists were women, male patients might have responded to receiving nonsexual therapeutic touch administered by a woman. This hypothesis could be tested, for example, by studying similar therapies administered to men by male therapists. At a minimum these results suggest that therapeutic massage may merit further study as a therapeutic alternative for UCPPS.
There were a number of strengths of our study. The standardization of treatment arms was across a number of centers, the recruitment of men and women was from sites throughout the United States, there was a high rate of adherence to the regimens in each treatment group, a high rate of assessment of the primary end point (low rate of loss to followup) and a broad range of domains was assessed as outcomes.
There were also several potential limitations of our study. It was not possible to blind study participants to treatment assignment as more than 90% were aware of their treatment group when queried at the end of the study. To compensate for this shortcoming we attempted to keep study coordinators unaware of participant treatment assignment. To make the GTM arm more similar to the MPT arm and to minimize un-blinding among participants we originally considered including weekly internal pelvic assessments in patients undergoing GTM. We ultimately decided that internal manipulation, which had no therapeutic intent, could not be justified. In addition, GTM was administered by physical therapists who may have consciously or unconsciously biased the outcome of therapy. To avoid such bias we considered having massage therapists administer GTM while physical therapists administered MPT. We abandoned this idea since the confounding of therapist with treatment would be an added disadvantage.
Importantly this randomized controlled trial was not designed to assess whether myofascial physical therapy is superior to massage therapy for treatment of UCPPS. Such a study would have to allow for optimization of MPT according to the physical abnormalities that are present, and according to response to treatments and performance of massage therapy treatments by licensed massage therapists. Although physical therapists receive some training in massage therapy and are all licensed to practice massage, this is not a therapeutic modality routinely used by most physical therapists. We elected to have our physical therapists perform MPT and GTM treatments to avoid the confounding of therapist and treatment that would have been present if we had decided to have physical therapists perform the MPT and massage therapists perform GTM. Importantly the GTM treatment used in this trial does not represent the standard of care for massage treatment and the results of this study should not be taken to mean that MPT is superior to massage therapy as would be practiced by an expert for UCPPS.
We also considered alternative comparison treatments including treatment with oral medication or with procedures such as sacral neuromodulation or acupuncture. We abandoned those study designs because alternative treatments that do not involve bodywork cannot provide us with an estimate of the treatment effect that is present simply through meeting weekly with a caring therapist who administers therapeutic touch.
CONCLUSIONS
Our initial encouraging results suggest that a full-scale clinical trial of myofascial physical therapy methods is possible and that MPT may offer meaningful clinical benefit to patients with UCPPS. To determine if our findings can be replicated we are now conducting a second small study comparing MPT and GTM (with a sample size of approximately 90) at 11 sites.
Abbreviations and Acronyms
| AE | adverse event |
| CP | chronic prostatitis |
| CPPS | chronic pelvic pain syndrome |
| CPSI | Chronic Prostatitis Symptom Index |
| CTM | connective tissue manipulation |
| FSFI | Female Sexual Function Index |
| GRA | global response assessment |
| GTM | global therapeutic massage |
| IC | interstitial cystitis |
| ICPI | O’Leary-Sant IC Problem Index |
| ICSI | O’Leary-Sant IC Symptom Index |
| MPT | myofascial physical therapy |
| NIH | National Institutes of Health |
| PBS | painful bladder syndrome |
| QOL | quality of life |
| SF-12 | 12-Item Short-Form Health Survey |
| UCPPS | urological chronic pelvic pain syndromes |
| UPPCRN | Urological Pelvic Pain Collaborative Research Network |
APPENDIX 1. Urological Pelvic Pain Collaborative Research Network Study Group
| Northwestern University/Rehab. Institute of Chicago | Stanford University |
| Colleen Fitzgerald, MD (Co-Investigator) | Rodney U. Anderson, MD (PI) |
| Suzanne Badillo, PT | Annemarie Cosby, PT |
| Cynthia E. Neville, PT | Angie Morey, MS |
| Darlene Marko, RN | Christopher K. Payne, MD (PI) |
| Cleveland Clinic | Laura C. Fraser, MPT |
| Jeannette Potts, MD (PI) | Debra Clay, RN |
| Elizabeth O’Dougherty, PT | Anna Ramakrishnan, MS |
| Donel Murphy, RN | University of Michigan Medical Center |
| William Beaumont Hospital | J. Quentin Clemens, MD (PI) |
| Kenneth Peters, MD (PI) | University of Pennsylvania School of Medicine |
| Lisa K. Odabachian, MPT, RN, BSN | J. Richard Landis, PhD (PI) |
| Andrea Sanfield, PT | Keith Mickelberg, RN, BSN |
| Eleanor Anton, RN | Marie Durborow |
| Loyola University | Ted Barrell, BS |
| Mary Pat Fitzgerald, MD (PI) | Shannon Chuai, MS |
| Rhonda K. Kotarinos, MS, PT | Liyi Cen, MS |
| Carole Fortman, PT | The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
| Rick Halle-Podell, LMT | John W. Kusek, PhD (Project Officer) |
| Judith Senka, RN | Leroy M. Nyberg, PhD, MD |
| Janet Rindels, RN | Christopher Mullins, PhD |
| Lucia Raducanu, RN |
APPENDIX 2. Inclusion, Exclusion and Deferral Criteria
Inclusion Criteria:
|
Exclusion Criteria:
|
Exclusion criteria for males only:
|
Exclusion criteria for females only:
|
| Deferral criteria: For men: within the last 24 weeks underwent transurethral prostate resection, transurethral prostate incision, transurethral bladder neck incision, transurethral thermotherapy, transurethral needle ablation, balloon dilation of the prostate, open prostatectomy, or any other prostate treatment such as cryotherapy or thermal therapy. For women: within the past 24 weeks has had vaginal delivery or cesarean section, transvaginal surgery, hysterectomy or prolapse surgery. |
APPENDIX 3. Primary Symptom Outcome Assessment Tool
| The global response assessment consists of the following question: “As compared to when you started the study, how would you rate your overall symptoms now?”
|
Participants who indicated they were 6 “moderately” or 7 “markedly” improved are considered intervention responders.
Footnotes
Clinical Trial Registration NCT00434343 (www.clinicaltrials.gov).