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

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

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.

Study Overview

• Status: Completed
• Conditions: Erectile Dysfunction
• Intervention / Treatment: Device: Aries ED device

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 54621
    • G.Gennimatas Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Consent to participate
2. Age >18
3. Presence of vasculogenic erectile dysfunction for at least 6 months
4. Positive response to PDE5i
5. IIEF-ED score > 6 and IIEF score < 26 after wash out of PDE5i
6. Abnormal penile triplex-based hemodynamic parameters (peak flow velocity <35cm/sec)
7. Stable heterosexual relationship for more than 3 months
8. Sexually active and agree to suspend all ED therapy for the duration of study

Exclusion Criteria:

1. Any cause of ED other than vascular related
2. Previous radiation therapy to pelvis
3. History of radical prostatectomy
4. Clinically significant chronic haematological disease
5. Cardiovascular conditions that prevent sexual activity
6. Peyronie's Disease or penile curvature
7. History of heart attack, stroke or any life- threatening arrhythmia within the prior 6 month
8. Anti-androgens oral or injectables androgens
9. Untreated Hypogonadism as demonstrated by abnormal testosterone levels
10. Malignancy within the past 5 years
11. Any unstable medical, psychiatric condition or spinal cord injury
12. Anatomical or neurological abnormalities in the treatment area
13. Use of any treatment for ED within 7 days of screening ( oral medications, vacuum devices, constrictive devices, injections or urethral suppositories)
14. Known allergy to ultrasound gel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A; 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; 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)
ACTIVE_COMPARATOR: Group B; 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; 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)
ACTIVE_COMPARATOR: Group C; 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; 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)
ACTIVE_COMPARATOR: Group D; 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; 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)

What is the study measuring?

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 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
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
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)

Collaborators and Investigators

• Sponsor: Institute for the Study of Urological Diseases, Greece

Publications and helpful links

General Publications

• Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the erectile function domain of the International Index of Erectile Function scale. Eur Urol. 2011 Nov;60(5):1010-6. doi: 10.1016/j.eururo.2011.07.053. Epub 2011 Jul 30.
• Clavijo RI, Kohn TP, Kohn JR, Ramasamy R. Effects of Low-Intensity Extracorporeal Shockwave Therapy on Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med. 2017 Jan;14(1):27-35. doi: 10.1016/j.jsxm.2016.11.001. Epub 2016 Dec 13.
• Lu Z, Lin G, Reed-Maldonado A, Wang C, Lee YC, Lue TF. Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis. Eur Urol. 2017 Feb;71(2):223-233. doi: 10.1016/j.eururo.2016.05.050. Epub 2016 Jun 16.
• Gruenwald I, Kitrey ND, Appel B, Vardi Y. Low-Intensity Extracorporeal Shock Wave Therapy in Vascular Disease and Erectile Dysfunction: Theory and Outcomes. Sex Med Rev. 2013 Jul;1(2):83-90. doi: 10.1002/smrj.9. Epub 2015 Oct 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 30, 2016
• Primary Completion (ACTUAL): June 6, 2018
• Study Completion (ACTUAL): December 10, 2018

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: March 20, 2017
• First Posted (ACTUAL): March 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 24, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Erectile Dysfunction; Low intensity extracorporeal shock wave treatment
• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Erectile Dysfunction
• Other Study ID Numbers: 13771/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No