Intracavernosal Injection of Botulinum Toxin Type A in the Treatment of Vascular Erectile Dysfunction

Study Overview
=================
Brief Summary
-----------------
Evidence has been arising that Botulinum toxin injections can relax smooth muscles fibers in the treatment of obesity and hyperactive bladder. Would a similar effect on cavernosal smooth muscles help in the treatment of resistant erectile dysfunction not responding to medical and injection therapy, thus avoiding surgical treatment options. The treatment group will be injected intracavernously with 50 units of BTX-A. The control group, 12 patients, will be injected with a normal saline injection.

Detailed Description
-----------------
24 males with will be included in the study. All 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 (12 patients) and a control group (12 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, 12 patients, 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 50 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. The rational for selecting the minimum 2-weeks waiting period is to give a chance for the BTX-A to reach its maximum effect. Possible Risks include pain and prolonged erections.

Official Title
-----------------
Intracavernosal Injection of Botulinum Toxin Type A in the Treatment of Vascular Erectile Dysfunction Not Responding to Oral and Intracavernous Therapy

Conditions
-----------------
Vasculogenic Erectile Dysfunction

Intervention / Treatment
-----------------
* Drug: Botulinum Toxin Type A
* Drug: Normal Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 24 males will be included in the study recruited from Andrology, Sexology & STD's outpatient clinic, Kasr El Aini Hospitals, Cairo University, complaining of Vascular ED proved by penile duplex. 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 40 to 70 years. Exclusion Criteria: Significant cardiovascular disease interfering with sexual activity

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (BTX) A Group<br>The treatment group will be injected intracavernously with a trimix solution for colour Doppler assessment, followed, on a separate day by 50 units of Botulinum toxin (BTX) A. | Drug: Botulinum Toxin Type A<br>* The treatment group will be injected intracavernously with a trimix solution (20 ug alprostadil + 1 mg phentolamine + 30 mg papaverine) for colour Doppler assessment, followed next day by 50 units of BTX-A.<br>|
| Placebo Comparator: Saline Group<br>The control group, 12 patients, will be injected with a trimix solution (20 ug alprostadil + 1 mg phentolamine + 30 mg papaverine) during penile colour Doppler assessment followed on a separate day with a normal saline injection. | Drug: Normal Saline<br>* The control group, 12 patients, will be injected with a trimix solution during penile colour Doppler assessment followed next day with a normal saline injection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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, before treatment. | Baseline | 
| 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 |
| --- | --- | --- |
| EHS Before Treatment | Clinical assessment of the Erection hardness score (EHS) in both groups after ICI at baseline. The Erection Hardness Score (EHS) is designed to measure the rigidity of erection. It ranges from 0 (no erection) to 4 (Fully rigid and hard erection). 0 - Penis does not enlarge. - Penis is larger, but not hard. - Penis is hard, but not hard enough for penetration. - Penis is hard enough for penetration, but not completely hard. - Penis is completely hard and fully rigid. The average score is reported for each group. | Baseline | 
| EHS After Treatment | Clinical assessment of the Erection hardness score (EHS) in both groups after ICI after 2 weeks. The Erection Hardness Score (EHS) is designed to measure the rigidity of erection. It ranges from 0 (no erection) to 4 (Fully rigid and hard erection). 0 - Penis does not enlarge. - Penis is larger, but not hard. - Penis is hard, but not hard enough for penetration. - Penis is hard enough for penetration, but not completely hard. - Penis is completely hard and fully rigid. The average score is reported for each group. | 2 weeks | 
| 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 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. | 1 month | 
| Global Assessment Question (GAQ) | Assessment of the effect of treatment by asking Has the treatment you have been taking improved your erectile function?. The number answering Yes in both the treatment and control groups are calculated. | 1 month | 
| SEP-Q2 Question Before Treatment | Number of patients answering Yes to the Sexual Encounter Profile question 2 (SEP-Q2: Were you able to insert your penis into your partner's vagina?) | Baseline | 
| SEP-Q2 Question After Treatment | Number of patients answering Yes to the Sexual Encounter Profile question 2 (SEP-Q2: Were you able to insert your penis into your partner's vagina?) after treatment. This analysis compares the number of patients who were able to perform vaginal intromission (insert the penis into the partner's vagina) after treatment in the (BTX) A group versus the Saline group. | 1 month | 
| SEP-Q3 Question Before Treatment | Number of patients answering Yes to the Sexual Encounter Profile question 3 (SEP-Q3: Did your erection last long enough for you to have successful intercourse?) before treatment. | Baseline | 
| SEP-Q3 Question After Treatment | Number of patients answering Yes to the Sexual Encounter Profile question 3 (SEP-Q3: Did your erection last long enough for you to have successful intercourse?) after treatment. This analysis compares the number of patients who were able to maintain their erection long enough to complete sexual intercourse after treatment in the (BTX) A group versus the Saline group. | 1 month |