Low-intensity Shockwave Therapy (LiST) for the Treatment of Mild and Mild-to-moderate Vasculogenic Erectile Dysfunction

Study Overview
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Brief Summary
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This is a randomized, double-blind, 2 parallel arms clinical trial. All patients will be PDE5I users/responders. After 1 month wash-out period, ED patients will be screened, in order to randomize 50 men with vasculogenic ED with primary objective to examine the efficacy of LiST using Aries2 device.

Official Title
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Low-intensity Shockwave Therapy (LiST) for the Treatment of Mild and Mild-to-moderate Vasculogenic Erectile Dysfunction: a Randomized Placebo Controlled Two-parallel Arms Trial, Comparing 6 Sessions, With Daily Tadalafil 5mg vs Placebo

Conditions
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Erectile Dysfunction, Low Intensity Shockwave Therapy

Intervention / Treatment
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* Other: DornierAries2 LiST device + 5 mg Tadalafil
* Other: DornierAries2 LiST device + Placebo Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consent to participate. Age 40-70 years. Sexually active in a stable, heterosexual relationship of more than three months duration. Presence of Erectile Dysfunction for at least 6 months. At Screening, diagnosed as Vasculogenic erectile dysfunction based on sexual history PDE5i users and report some or good response to PDE5i. Last reported PDE5i use must be within 30 days of Screening Visit. Agree to suspend all other ED therapies, except the assigned study treatments, for the duration of the study. Agree to attempt sexual intercourse at least 4 times during the last 4 weeks prior to Visit 2/Randomization, 1-month Follow Up, 3-month Follow-Up and 6-month Follow-Up without being under the influence of alcohol or recreational drugs. Agree to document the outcome using the Sexual Encounter Profile (SEP) diary. IIEF-EF score 17-25 at Visit 2 (after PDE5i washout) At Visit 2 (after PDE5i washout), SEP Q2, Were you able to insert your penis into your partner's vagina? answered YES 50% - 100% of the time. At Visit 2, SEP Q3, Did your erection last long enough for you to have successful intercourse? answered YES < 100% of the time. Exclusion Criteria: Previous major pelvic surgery or pelvic trauma that could impact erectile function, such as radical prostatectomy, radical cystectomy, rectal surgery. Patients with previous TURP surgery without sequelae of iatrogenic ED, may be included. Previous penile surgery of any kind except circumcision and condyloma removal, such as penile lengthening, penile cancer surgery, penile plication, grafting. Previous history of priapism or penile fracture Previous radiation therapy to pelvis. Abnormal serum testosterone level defined as a value lower than 300 ng/dL (indicative of untreated hypogonadism), or greater than 1197 ng/dL. Current or previous hormone usage, other than prescribed testosterone, clomiphene or thyroid medication. Subjects with prior or current use of hormonal treatment for prostate cancer are also excluded. ED due primarily to psychogenic factors. Peyronie's Disease or penile curvature that negatively influences sexual activity. Patients with cardiac or non-cardiac electrical devices implanted. Open wounds, or any anatomical or neurological abnormalities in the treatment area. Uncontrolled diabetes mellitus with glucose >200 mg/dL (once or more times/week during the last month prior to recruitment, or during screening blood test). Patients with generalized polyneuropathy, or neurological conditions irrespective of cause, such as severe diabetes, multiple sclerosis or Parkinson's Disease. Refusal to suspend alternative ED therapy for duration of study. Subjects who are using Tadalafil as a treatment for BPH (Benign Prostatic Hyperplasia) will also be excluded. Men deemed not healthy enough to participate in sexual activity. Any condition or behavior that indicates to the Principal Investigator that the subject is unlikely to be compliant with study procedures and visits. Any health history or laboratory result that indicates to the Principal Investigator that the subject has a significant medical condition and should not participate in the study. Known allergy to ultrasound gel. History of consistent treatment failure with PDE5 inhibitors for therapy of ED. Any history of significant psychiatric disease, such as bipolar disorder or psychosis, greater than one lifetime episode of major depression, current depression of moderate or greater severity. Patients who are currently using SSRI or psychotropic medications e.g., Citalopram (Celexa), Escitalopram (Lexapro, Cipralex), Paroxetine (Paxil, Seroxat), Fluoxetine (Prozac), Fluvoxamine (Luvox, Faverin),Sertraline (Zoloft, Lustral), Clonazepam (Klonopin), Alprazolam (Xanax), Aripiprazole (Ambilify), Clozapine (Clozaril), Risperidone (Risperdal), Quetiapine (Seroquel), Olanzapine (Zyprexa) are also excluded. Partners who are < 18 years of age, who are nursing, who are known to be pregnant at screening, who wish to become pregnant during the study period, who have any gynecologic problems, sexual dysfunction, or major medical conditions that would limit participation in sexual intercourse. History of adverse events in response to tadalafil, which would prevent the patient from being blinded to his group allocation, and/or prevent patient compliance to the study protocol.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LiST + 5mg Tadalafil Group<br>All patients will receive shockwave treatment (6 sessions for all subjects, 5000 shockwaves at each session, at energy level 7), twice per week (total of 3 weeks) without treatment interval. Starting at first LiST session and finishing one week after final LiST session, subjects will receive for 4 weeks daily Tadalafil 5mg. Total treatment period = 4 weeks. | Other: DornierAries2 LiST device + 5 mg Tadalafil<br>* All patients will receive shockwave treatment (6 sessions for all subjects, 5000 shockwaves at each session, at energy level 7), twice per week (total of 3 weeks) without treatment interval. Starting at first LiST session and finishing one week after final LiST session, subjects will receive for 4 weeks daily Tadalafil 5mg. Total treatment period = 4 weeks<br>|
| Placebo Comparator: LiST+Placebo Group<br>All patients will receive shockwave treatment (6 sessions for all subjects, 5000 shockwaves at each session, at energy level 7), twice per week (total of 3 weeks) without treatment interval. Starting at first LiST session and finishing one week after final LiST session, subjects will receive for 4 weeks daily placebo pill. Total treatment period = 4 weeks. | Other: DornierAries2 LiST device + Placebo Pill<br>* All patients will receive shockwave treatment (6 sessions for all subjects, 5000 shockwaves at each session, at energy level 7), twice per week (total of 3 weeks) without treatment interval. Starting at first LiST session and finishing one week after final LiST session, subjects will receive for 4 weeks daily Placebo pills. Total treatment period = 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Erectile Function domain score of the International Index of Erectile Function (IIEF-EF) | EF domain of the IIEF questionnaire will be completed.IIEF-EF consists of items 1,2,3,4,5,15 of the IIEF questionnaire.According to the score of the iIEF-EF there are five categories of erectile function: 1-10 (Severe Erectile Dysfunction), 11-16(Moderate dysfunction), 17-21(Mild to moderate dysfunction), 22-25(Mild dysfunction), 26-30 (No dysfunction) | baseline and 12-week follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Erectile Function domain score of the International Index of Erectile Function (IIEF-EF) | EF domain of the IIEF questionnaire will be completed.IIEF-EF consists of items 1,2,3,4,5,15 of the IIEF questionnaire.According to the score of the iIEF-EF there are five categories of erectile function: 1-10 (Severe Erectile Dysfunction), 11-16(Moderate dysfunction), 17-21(Mild to moderate dysfunction), 22-25(Mild dysfunction), 26-30 (No dysfunction) | baseline and 4-week follow-up visit | 
| Change in the Erectile Function domain score of the International Index of Erectile Function (IIEF-EF) | EF domain of the IIEF questionnaire will be completed.IIEF-EF consists of items 1,2,3,4,5,15 of the IIEF questionnaire.According to the score of the iIEF-EF there are five categories of erectile function: 1-10 (Severe Erectile Dysfunction), 11-16(Moderate dysfunction), 17-21(Mild to moderate dysfunction), 22-25(Mild dysfunction), 26-30 (No dysfunction) | baseline and 24-week 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.The Sexual Encounter Profile (SEP) is a log diary completed after each sexual attempt, providing information as to whether the erection was hard enough to penetrate (SEP 2), or whether it was maintained for completion (SEP 3) or a satisfactory sexual experience (SEP 4). SEP 3 exact question is Did your erection last long enough for you to have successful intercourse? | baseline and 4-week 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.The Sexual Encounter Profile (SEP) is a log diary completed after each sexual attempt, providing information as to whether the erection was hard enough to penetrate (SEP 2), or whether it was maintained for completion (SEP 3) or a satisfactory sexual experience (SEP 4). SEP 3 exact question is Did your erection last long enough for you to have successful intercourse? | baseline and 12-week 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.The Sexual Encounter Profile (SEP) is a log diary completed after each sexual attempt, providing information as to whether the erection was hard enough to penetrate (SEP 2), or whether it was maintained for completion (SEP 3) or a satisfactory sexual experience (SEP 4). SEP 3 exact question is Did your erection last long enough for you to have successful intercourse? | baseline and 24-week 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 6 month follow up period will be reported | 28 weeks |