Safety and Efficacy of Low Intensity Shockwave for the Treatment of Erectile Dysfunction
Condition: Vasculogenic Erectile Dysfunction
MeSH terms: Erectile Dysfunction
Study type: Interventional

Summary: 
      Renova- Erectile Dysfunction (ED) is a Linear Shockwaves (LISW) device which incorporates a
      unique shockwave transducer operable to deliver shockwaves to a treated region. Shockwaves
      are aimed at the left and right corpora cavernosa and the crura. The study is aimed at
      determining the safety and effectiveness of this new type LISW in the relief of erectile
      dysfunction.

      HYPOTHESIS Alternate Hypothesis (HA): Active Treatment groups will show a >2-point increase
      in the IIEF-EF score from baseline for mild erectile dysfunction, and >5 points for moderate
      erectile dysfunction and will show significant change.

      Null Hypothesis (HO): There is no difference from baseline and after-treatment in Treatment
      groups for alleviating erectile dysfunction measured using International Index of Erectile
      Function score (IIEF-EF).

      Primary Efficacy Objective: To evaluate change of International Index of Erectile Function
      score Questionnaire score from baseline to follow-ups 1, 3 and 6 months' post treatment.

      Secondary Objectives:To study sexual activity improvement leading to optimal penetration at
      follow-ups according to:

        -  SEP- Sexual Encounter Profile Questionnaire.

        -  GAQ- Global Assessment Questionnaire.

        -  EHS- Erection Hardness Score.
    

Detailed description: 
      Renova-Erectile dysfunction (ED) is a Linear Shockwaves (LISW) device which incorporates a
      unique shockwave transducer operable to deliver shockwaves to a treated region confined to a
      narrow rectangle. Shockwaves generation follows the electromagnetic principle.

      Linear Shockwaves (LISW), as a treatment for erectile dysfunction has been in evaluation in
      contemporary medicine, It has been in use for the last three years.

      The present study is about a device called "Renova-erectile dysfunction", in which shockwaves
      are focused onto line segments for improved organ coverage. Shockwaves produced by
      "Renova-erectile dysfunction" are aimed at the left and right corpora cavernosa and the
      crura. The study is aimed at determining the safety and effectiveness of this new type LISW
      in the relief of erectile dysfunction.

      Rationale:Linear Shockwaves has been known to bolster angiogenesis by increasing the levels
      of vascular endothelial growth factor.

      Principal mode of action used in other disease:

        -  Coronary Artery Disease: Kikuchi et al.3 showed significantly improved symptoms and
           decreased nitroglycerin use in patient who had a coronary artery bypass grafting and
           were suffering from stable angina.

        -  Bone Healing: Haupt et al.4 showed that Low intensity shock waves treated group showed
           radiological signs of faster healing.

        -  Calcifying tendinitis: Rompe et al.5 showed that shock wave to patient suffering from
           calcifying tendinitis showed a 62.5% partial and complete disintegration of the the
           deposits. Moreover, 85% of the patients reported improvement at 24-week follow up
           period.

        -  Diabetic Foot Ulcers: Wang et al.6 showed that Extracorporeal Shock Wave Therapy (ESWT)
           to patients with diabetic foot ulcer showed complete improvement in 31% and partial
           improvement in 58%.Moreover,Extracorporeal Shock Wave Therapy showed significantly
           better clinical results and local blood flow perfusion, higher cell concentration, and
           activity than the Hyperbaric Oxygen group.

      Preliminary Studies:

      Contemporary literature shows two important studies in this field both conducted by Verdi et
      al.

      The efficacy trial study published in 2010 recruited 20 men with vasculogenic erectile
      dysfunction and were given serial 2 sessions of treatment for about 3 weeks followed by 3 -
      week no intervention period. At 1-month duration there was a significant improvement in their
      erectile function measured by International Index of Erectile Function domain scores (20.9
      5.8 vs 13.5 4.1, p < 0.001). This significant result was consistent at 6-month follow up.
      Moreover, no pain or adverse event was noted during the follow-up period.

      The second randomized, double-blind, sham controlled study by showed that treatment group
      showed better outcome than control group measured using International Index of Erectile
      Function-Erectile Function domain (mean square root of sample size 6.7 0.9 vs 3.0 1.4, p
      0.0322) at the first follow-up. Additionally, penile hemodynamics improve significantly in
      the treatment group in comparison to control group (maximal post-ischemic penile blood flow
      8.2 vs 0.1 ml per minute per dl, p 0.0001).

      Primary Efficacy Objective:To evaluate change of Erectile Function-Erectile Function score 9
      from baseline to follow-ups 1, 3 and 6 months' post treatment.

      Secondary Objectives:To study sexual activity improvement leading to optimal penetration at
      follow-ups according to:

        -  SEP- Sexual Encounter Profile.

        -  GAQ- Global Assessment Questions.

        -  EHS- Erection Hardness Score.

      STUDY DESIGN Accrual goal: A total of 80 patients with Vasculogenic erectile dysfunction
      meeting the eligibility criteria will be recruited from the Department of Urology clinic.

      Duration of Study Participation: The total duration of the study will be for 7 months-
      including 1-month pretreatment (washout) followed by a period of 6 months' follow-up after
      the treatment.

      Screening Evaluations and Procedures: The first visit of the patients will be for screening
      and medical evaluation. Patient's medical co-medication history will be collected and
      documented and a physical examination will be performed.

      Previous month's blood test results will be reviewed including a general chemistry panel, a
      lipid profile, hemoglobin A1C and testosterone levels during chart review.

      Patients will sign an informed consent and will answer the Erectile Function-Erectile
      Function questionnaire to see if they fit the criteria for enrollment. In case they meet all
      inclusion criteria (and do not meet any exclusion criteria), they will be recruited to the
      study.

      Patients who have been using phosphodiesterase 5 inhibitor (PDE5-i) in the last 4 weeks will
      report on their medicine type and dosage, and this data will be recorded in their files
      (reported prior to consent and gathered from chart review).

      Pre-Treatment Procedures and Evaluations : Upon evaluating the inclusion/exclusion criteria,
      patients will be recruited to the study and randomized into one of the two groups in a 1:1
      ratio (randomization will be performed by a computer software maintained by the Department of
      Urology). Patients randomized to the treatment groups will be instructed to stop any use of
      phosphodiesterase 5 inhibitor for 4 weeks prior to first treatment session and refrain from
      using any other erectile dysfunction therapy option during the study. They will be instructed
      to undergo a phosphodiesterase 5 inhibitor washout period of 4 weeks prior to treatment and
      to avoid using phosphodiesterase 5 inhibitor or any other erectile dysfunction treatment
      during the entire study duration (shockwave treatment and follow-ups). After the washout
      period and before the first treatment session, patients will answer the IIEF-EF, SEP and EHS
      questionnaires for baseline evaluation.

      Treatment procedure: The treatment session lasts approximately 20 minutes and may be
      performed in an office environment. Treatment is applied in the physician's office. For
      session and treatment details (see below)

      During the treatment, the same total number of shocks will be delivered according to the two
      treatment schedules as follows:

      Group A:

      5 daily sessions within a week (Monday, Tuesday, Wednesday, Thursday, Friday (MTWThF), in
      which 720 shocks of treatment energy will be applied in every session to each treated region
      (left and right corpora cavernosa and crura).

      Group B:

      Three sessions per week Monday, Wednesday, Friday (MWF) for 2 consecutive weeks, in which 600
      shocks of treatment energy will be applied in every session to each treated region (left and
      right corpora cavernosa and crura)

      Following the last treatment session, each patient will resume his baseline consumption of
      phosphodiesterase 5 inhibitor, in terms of type and dose of drug, for the remainder of study
      duration.

      Follow-Up Procedures and Evaluations:Follow-up visits will be conducted at month 1, month 3
      and month 6 after the last treatment session and shall include:

      Measuring IIEF-EF, GAQ, SEP, and EHS scores of patients at the clinic at every follow-up
      visit

      Reporting and recording adverse events at every follow-up visit.
    

Intervention name(s): Low Intensity Linear Shockwave Device for the Treatment of Erectile Dysfunction.
Intervention type(s): Device
Intervention description(s): This is a prospective, randomized, clinical study aimed to evaluate the safety and efficacy of the two treatment schedules on symptomatic erectile dysfunction patients. The patients are randomized in a 1:1 ratio into two active treatment groups.
Group A: 5 daily sessions within a week (Monday, Tuesday, Wednesday, Thursday, Friday), in which 720 shocks of treatment energy will be applied in every session to each treated region (left and right corpora cavernosa and crura).
Group B: Three sessions per week (Monday, Wednesday, Friday) for 2 consecutive weeks, in which 600 shocks of treatment energy will be applied in every session to each treated region (left and right corpora cavernosa and crura)
.
Other intervention name(s): RENOVA-ED
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment