Low-energy Extracorporeal Shockwave Treatment for Patients After Radical Prostatectomy

Study Overview
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Brief Summary
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The purpose of this project is to verify the relationship between low intensity shock wave treatment (LI-SWT) and increased scores in self-assessment regarding to erectile function (ED) and sexual intercourse, in patients, who has undergone a radical prostatectomy (RP). The data will be obtained from patients using international accepted sexual questionnaires prior to the LI-SWT and 5, 12 and 24 weeks following treatment.

Detailed Description
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Extracorporeal shockwave therapy (ESWT) has been used for many years in different fields. In 1980, the clinical use of extracorporeal shockwave lithotripsy as a treatment for stone disease in the upper urinary tract began and proved effective. Throughout the years, ESWT has been modified for use in other specialties, such as in the treatment of gallstones, sialolithiasis and Peyronie's disease. Animal studies have demonstrated neoangiogenesis in myocardial tissue and skin flaps as well as regeneration of nervous tissue. Gotte et al. found that shock waves can, under suitable conditions, lead to non-catalytic synthesis of physiologically relevant quantities of NO. These pioneering findings corroborate our hypothesis that ED due to RP, can likely be treated by LI-SWT. It is well known that patients radically operated for prostate cancer subsequently develop erectile dysfunction (ED) and /or urinary incontinence. A meta-analysis from 2009 found that the overall erection recovery rate after prostatectomy were 58%, meaning that a certain amount of patients still suffer from ED in the postoperative lifespan. The investigators want to investigate in a randomized trial whether LI-ESWT is efficient in ED patients, who has undergone RP, regarding to sexual function. These data will be assessed by changes in outcome of sexual questionnaire regarding to sexual function and erection hardness. This hypothesis has previous been tested in a Danish pilot study. The study design was a prospective cohort study with 16 participants all suffering from ED due to nerve sparing RD. The participants received two series of LI-ESWT per week in a 3-week period. The results indicated a gradual increase in erectile function at the 1 month follow up, evaluated by cross matching the IIEF-15 scores before and after treatment. However, the effect was damped off at the last follow up one year later. The pilot study concluded that more research had to be done in a larger population group. The study design is decided to be a prospective, blinded, randomized placebo-control follow up design. The total enrol of participants are estimated to be sixty-four divided into a placebo group and an active group. The participants who meet the inclusions criteria (see section below) will be randomly assigned to either a control group (P) or an active group based (V) on a randomization list. The treatment sessions will take place at the outpatient clinic of the department of urology L, OUH. The shock wave device used for this study is a duolith® SD1 T-Top from Storz Medical (see fig. 2). The device is set at 0.15 mJ/mm2, 5 Hz, with a total of 3000 impulses, and a total energy of 12.8 J per treatment. LI-ESWT will be performed in six positions on the penis (distal, center and proximal part of each cavernous body) and given by a therapist educated for the purpose. The cap used to prevent LI-SWT in the placebo group will be positioned by the Head of the Department to ensure valid blinding. Prior to the treatment, the participants will be asked to fulfil questionnaires (EHS, IIEF-15 and DAN-PSS) to assess data on lower urinary tract symptoms, sexual dysfunction and erection hardness. At the first treatment session (baseline function), the investigator reviews the questionnaires in cooperation with the participant to ensure no conflicts and misunderstanding in questions. There will be a total of 5 treatment sessions during a 5-week period. Shortly after treatment, the participants will be asked to fill in the questionnaires once again. The questionnaires will be mailed to the participants home addresses together with a prepaid return envelope and asked to be reposted at 5th, 12th and 24th week respectively.

Official Title
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A Prospective Randomized Study Whether Low-energy Extracorporeal Shockwave Therapy (LI-ESWT) Can Increase Erectile Function in Patients After Radical Prostatectomy

Conditions
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Erectile Dysfunction, Post-Op Complication, Prostatic Diseases

Intervention / Treatment
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* Procedure: Low intensity extracorporeal shock wave treatment (LI-ESWT)
* Procedure: Low intensity extracorporeal shock wave treatment (LI-ESWT) sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Erectile dysfunction for more than 6 months, Time since prostatectomy must be at least 9 month At least unilateral nerve-sparing RP. Erection Hardness Score (EHS) less than 2 and an Index of Erectile Function (IIEF-5) score less than 17 Age 20-80 years have been in a relationship for more than 3 months. Participant can give informed consent. Exclusion Criteria: Men with ED due to other reason than RD (psychogenic, neurological pathology or organic ED etc.) Rectal extirpation, radiation therapy to the pelvic area and recovery from any other cancer within the past 5 years are excluded. Participants with heart disease prohibiting sexual activity or taking medication with antiandrogens, anticoagulant (apart from aspirin) or systemic use of glucocorticoids within 5 weeks. ED treatment within the last 7 days (screening phase), oral medication, vacuum devices, injections.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment<br>This group of participant will receive low intensity shock wave treatment accounted on their penile shaft once every week for 5 weeks. | Procedure: Low intensity extracorporeal shock wave treatment (LI-ESWT)<br>* Shock wave treatment with 3000 Hz for 10 min on the penile shaft. This will be done one time a week for five weeks.<br>* Other names: DUOLITH® SD1;|
| Placebo Comparator: Placebo group<br>this group of participant will meet up for treatment. The treatment given will be the exact same as the active group, but the transducer used for shock wave treat will me capped, meaning that no shock waves are transmitted to their penis. | Procedure: Low intensity extracorporeal shock wave treatment (LI-ESWT) sham<br>* A specialized cap can be applied to the chock wave device, which disallow shock waves to transmit through the unit.<br>* Other names: DUOLITH® SD1 with cap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erection hardness score (EHS) Baseline | A five entity questionnaire to review the self-esteem of erection during sexual intercourse. The questionnaire will be mailed to the participants home adresses together with a return envelope. | 2 weeks prior first treatment | 
| Erection hardness score first follow up | A five entity questionnaire to review the self-esteem of erection during sexual intercourse. The questionnaire will be mailed to the participants home adresses together with a return envelope. | 5 weeks after last treatment | 
| Erection hardness score second follow up | A five entity questionnaire to review the self-esteem of erection during sexual intercourse. The questionnaire will be mailed to the participants home adresses together with a return envelope. | 12 weeks after last treatment | 
| Erection hardness score third follow up | A five entity questionnaire to review the self-esteem of erection during sexual intercourse. The questionnaire will be mailed to the participants home adresses together with a return envelope. | 24 weeks after last treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The International index of erection function (IIEF-5) baseline | A fifteen item questionnaires to access data on erection function. Only question 1-5 will be used in for data interpretation. These item is also called til erection function domain (EF domain) | 2 weeks prior first treatment | 
| The International index of erection function (IIEF-5) first follow up | A fifteen item questionnaires to access data on erection function. Only question 1-5 will be used in for data interpretation. These item is also called til erection function domain (EF domain) | 5 weeks after last treatment | 
| The International index of erection function (IIEF-5) second follow up | A fifteen item questionnaires to access data on erection function. Only question 1-5 will be used in for data interpretation. These item is also called til erection function domain (EF domain) | 12 weeks after last treatment | 
| The International index of erection function (IIEF-5) third follow up | A fifteen item questionnaires to access data on erection function. Only question 1-5 will be used in for data interpretation. These item is also called til erection function domain (EF domain) | 24 weeks after last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shock wave therapy, erectile dysfunction