Low Intensity Extracorporeal Shock Wave Treatment for Erectile Dysfunction: Standardisation of Treatment Protocol

Study Overview
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Brief Summary
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The present study aims to identify the efficacy saturation effect of low intensity extracorporeal shockwave treatment (LI-ESWT) using Aries ED device in men with mild-moderate and severe vasculogenic ED, who have previously responded to oral PDE5-Is. The efficacy and safety of 4 different session frequency protocols will be compared.

Detailed Description
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This is a randomized, 4 parallel arms, clinical trial with an 18-month recruitment period. All patients will be PDE5I users/responders. After 1 month wash-out period, ED patients will be screened, in order to randomize 96 men with vasculogenic ED, an International Index of Erectile Function ED (IIEF-ED) domain score between 6-25 and abnormal penile triplex-based hemodynamic parameters (peak flow velocity <35cm/sec) in the last 6 months. Additionally, they will be asked to complete the SEP diaries. Patients will be randomized to receive shockwave treatments (12 sessions for all subjects), either twice a week (total of 6 weeks) or three times a week (total of 4 weeks) at energy level 4 or 7, without treatment interval. Study visits and duration Visit 1 (day 0): the basic work-up will take place, including medical and sexual history, as well as necessary lab tests, if needed. One month wash-out period will follow. During this period, all subjects will be asked to avoid any drug related to ED (PDE5i) and have at least 2-4 attempts for intercourse. Furthermore, patients will undergo triplex ultrasonography, unless they have already done so in the last 6 months.Also penile dimensions in both flaccid and erect state will be measured. Visit 2 (day 28 + 3 days): all patients will complete the IIEF-ED domain and will be randomized to one of the four parallel study groups, using an online program. Groups A and C will receive treatment twice per week, at energy level 4 and 7 respectively. Groups B and D will receive treatment three times per week, at energy level 4 and 7 respectively. PDE5i use is prohibited throughout the study. Treatment Visits: There will be 12 active treatment visits for all 4 Groups. Patients will receive LI-ESWT, according to the study protocol. Interval between 2 treatments will be 3+1 days for Groups A and C (twice/week) whereas 1+1 day for Groups B and D (three times/week). At visit 6 and 12 a penile ultrasonography will be conducted in order to check for potential adverse events related to the treatment. Follow-up visits 1 - 3 (4, 12 ,24 and 48 weeks post treatment): Patients will complete the IIEF-ED questionnaire and return the completed SEP diaries for the last 4 weeks prior to every visit. Visit data will also be recorded (protocol compliance, adverse events). At Week 12, triplex will be performed by the standard protocol. For Week 4 there is a + 3 days visit window, whereas for weeks 12, 24 and 48 there is a + 2 weeks visit window.

Official Title
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Low Intensity Extracorporeal Shock Wave Treatment Patients With Vasculogenic Erectile Dysfunction: Standardisation of Treatment Protocol

Conditions
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Erectile Dysfunction

Intervention / Treatment
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* Device: Aries ED device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consent to participate Age >18 Presence of vasculogenic erectile dysfunction for at least 6 months Positive response to PDE5i IIEF-ED score > 6 and IIEF score < 26 after wash out of PDE5i Abnormal penile triplex-based hemodynamic parameters (peak flow velocity <35cm/sec) Stable heterosexual relationship for more than 3 months Sexually active and agree to suspend all ED therapy for the duration of study Exclusion Criteria: Any cause of ED other than vascular related Previous radiation therapy to pelvis History of radical prostatectomy Clinically significant chronic haematological disease Cardiovascular conditions that prevent sexual activity Peyronie's Disease or penile curvature History of heart attack, stroke or any life- threatening arrhythmia within the prior 6 month Anti-androgens oral or injectables androgens Untreated Hypogonadism as demonstrated by abnormal testosterone levels Malignancy within the past 5 years Any unstable medical, psychiatric condition or spinal cord injury Anatomical or neurological abnormalities in the treatment area Use of any treatment for ED within 7 days of screening ( oral medications, vacuum devices, constrictive devices, injections or urethral suppositories) Known allergy to ultrasound gel

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Patients will receive 2 sessions of LI-ESWT per week for a 6 week period with energy level 4 (12 sessions totally) | Device: Aries ED device<br>* The Dornier Aries-ED device will be used for the purpose of the study. LI-ESWT will be applied to the penile shaft 3 areas, and the 2 crura (two sites)<br>|
| Active Comparator: Group B<br>Patients will receive 3 sessions of LI-ESWT per week for a 4 week period with energy level 4 (12 sessions totally) | Device: Aries ED device<br>* The Dornier Aries-ED device will be used for the purpose of the study. LI-ESWT will be applied to the penile shaft 3 areas, and the 2 crura (two sites)<br>|
| Active Comparator: Group C<br>Patients will receive 2 sessions of LI-ESWT per week for a 6 week period with energy level 7 (12 sessions totally) | Device: Aries ED device<br>* The Dornier Aries-ED device will be used for the purpose of the study. LI-ESWT will be applied to the penile shaft 3 areas, and the 2 crura (two sites)<br>|
| Active Comparator: Group D<br>Patients will receive 3 sessions of LI-ESWT per week for a 4 week period with energy level 7 (12 sessions totally) | Device: Aries ED device<br>* The Dornier Aries-ED device will be used for the purpose of the study. LI-ESWT will be applied to the penile shaft 3 areas, and the 2 crura (two sites)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of subjects who achieve clinically important difference (MCID) in the EF domain score of the IIEF | MCID is defined according to baseline ED severity as: Improvement by 2 or more in the EF domain score of the IIEF for patients with mild ED ( EF scores 17-25) at baseline. Improvement by 5 or more in the EF domain score of the IIEF for patients with moderate ED(EF scores 11-16) at baseline Improvement by 7 or more in the EF domain score of the IIEF for patients with severe ED (EF scores 0-10) at baseline | baseline and 6 month follow up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the EF domain score of the IIEF | EF domain of the IIEF questionnaire will be completed | baseline, 6 month follow up visit and 12 month follow up visit | 
| Change in Sexual Encounter Profile Question 3 (SEP3) score | The percent of subjects who answer ''YES'' in question 3 of SEP questionnaire will be reported | baseline, 6 month follow up visit and 12 month follow up visit | 
| Change in mean peak systolic velocity (PSV) | Mean peak systolic velocity will be measured by penile triplex ultrasonography by the same investigator. | baseline and 3 month follow up visit | 
| Number of patients with treatment related adverse events | Potential treatment related adverse events after the first LI-ESWT session and during the 12 month follow up period will be reported | 54 weeks (Group A and Group C), 52 weeks (Group B and Group D) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erectile Dysfunction, Low intensity extracorporeal shock wave treatment