Botulinum Toxin for Erectile Dysfunction

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of intra-cavernosal Botulinum toxin injection as an alternative line of treatment in patients with erectile dysfunction - not responding to oral PDE5i - through cavernosal smooth muscle relaxation.

Detailed Description
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The initial Phase 1 study demonstrated safety and efficacy of Botulinum toxin type A in the treatment of Erectile dysfunction in a small randomized controlled trial of 24 men. The investigators conduct a phase 2 trial to confirm the initial results in a larger group of men.70 males will be included in the study. The participants will be subjected for full history taking, general and genital examination. Penile duplex will be performed to assess a vascular etiology before the treatment and 2 weeks later. The patients will be randomized into a treatment group (35 patients) and a control group (35 patients). All patients will sign an informed consent. The treatment group will be injected IC with a trimix solution (20 ug alprostadil + 1 mg phentolamine + 30 mg papaverine) for color Doppler assessment, followed, next day by 50 units of BTX-A. The control group will be injected with the trimix solution during penile color Doppler assessment followed next day with a normal saline injection. The erection hardness score (EHS) will be assessed during the Doppler exam. Procedure: At least 1 day after the penile color Doppler test, the patient is placed in the supine position flaccid and stretched penile length and girth would be measured from tip of the penis to the pubic bone will be done. A rubber band will be applied to the base of the penis. The skin will be prepped with alcohol swabs followed by the IC injection of 100 units of BTX-A. Direct pressure will be applied for 2 minutes. The rubber band will be removed after 15 minutes. Patients and controls will fill the Sexual Health Inventory for men (SHIM) questionnaire and answer the the Sexual Encounter Profile questions 1 and 2 (SEP 2 & SEP 3), and the global assessment question (GAQ) before and 4 weeks after treatment.

Official Title
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Intracavernosal Injection of Botulinum Toxin Type A in the Treatment of Erectile Dysfunction (Phase 2 Study)

Conditions
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Sexual Dysfunction, Erectile Dysfunction

Intervention / Treatment
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* Drug: Botulinum Toxin Type A
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 70 males will be included in the study recruited from Andrology, Sexology & STD's outpatient clinic, Kasr El Aini Hospitals, Cairo University, complaining of ED. Unable to develop erections sufficient for intercourse. Failing to respond to first line and second line treatments for Erectile Dysfunction with surgery as the only remaining treatment option. Age between 18 to 80 years. Exclusion Criteria: - Significant cardiovascular disease interfering with sexual activity

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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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
Interventional Model Description: Prospective, randomized double blind placebo control ( RDBPC) study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botulinum Toxin Type A (BTX-A) Group<br>Experimental: BTX-A Group The treatment group, 35 patients, will be injected with 100 units BTX-A one day following penile colour Doppler assessment. | Drug: Botulinum Toxin Type A<br>* Drug: Botulinum Toxin Type A The treatment group will be injected with 100 units BTX-A one day following penile colour doppler assessment.<br>|
| Placebo Comparator: Placebo Group<br>Saline Group: The control group, 35 patients, will be injected with 1 ml normal saline one day following penile colour Doppler assessment. | Drug: Normal saline<br>* The treatment group will be injected with 1 ml normal saline one day following penile colour doppler assessment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV Before Treatment | Baseline mean Peak systolic velocity (PSV) in the Cavernosal arteries, on color Doppler examination, in the patient and control groups. | Baseline | 
| Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV After Treatment | Cavernosal artery mean peak systolic velocity (PSV) after treatment, on color Doppler examination, in the patient and control groups. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SHIM Score Before Treatment | Assessment of the Sexual Health Inventory for men (SHIM) questionnaire before treatment for both groups. It is a questionnaire that helps asses if the patient has erectile dysfunction (ED) and assesses its degree. Results range from 1 to 25. A score of 1-7 denotes Severe ED, 8-11 Moderate ED, 12-16, Mild to Moderate ED, 17-21 Mild ED, 22-25 No ED. | Baseline | 
| SHIM Score After Treatment | Assessment of the Sexual Health Inventory for men (SHIM) questionnaire after treatment for both groups. It is a questionnaire that helps to asses if the patient has erectile dysfunction (ED) and to assess its degree. Results range from 1 to 25. A score of 1-7 denotes Severe ED, 8-11 Moderate ED, 12-16, Mild to Moderate ED, 17-21 Mild ED, 22-25 No ED. Minimum value is 1, Maximum value is 25, the higher the score the better is the outcome. | 2 weeks after injection. | 
| SHIM Score After Treatment | Assessment of the Sexual Health Inventory for men (SHIM) questionnaire after 6 and 12 weeks of both groups. It is a questionnaire that helps to asses if the patient has erectile dysfunction (ED) and to assess its degree. Results range from 1 to 25. A score of 1-7 denotes Severe ED, 8-11 Moderate ED, 12-16, Mild to Moderate ED, 17-21 Mild ED, 22-25 No ED. Minimum value is 1, Maximum value is 25, the higher the score the better is the outcome. | 6 and 12 weeks after injection. | 
| Penile Size Before Treatment | Measurement of penile length before treatment: Flaccid, stretched and erect penile length. | Baseline | 
| Penile Size After Treatment | Measurement of penile length after treatment. | 2 weeks after injection. | 
| Penile Size After Treatment | Measurement of penile length after treatment. | 6 and 12 weeks after injection. | 
| Intra-vaginal Latency Time Before Treatment | Measurement of the duration of intercourse from intromission to ejaculation before treatment. | Baseline | 
| Intra-vaginal Latency Time After Treatment | Measurement of the duration of intercourse from intromission to ejaculation after treatment. | 2 weeks after injection. | 
| Intra-vaginal Latency Time After Treatment | Measurement of the duration of intercourse from intromission to ejaculation after treatment. | 6 and 12 weeks after injection. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erectile dysfunction, Botulinum toxin A, Botox