Vasculogenic Erectile Dysfunction
Conditions
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.
Interventions
DRUGBotulinum Toxin Type A
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.
DRUGNormal Saline
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.
Sponsors
Cairo University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
40 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cavernosal Artery Mean PSV Before Treatment | Baseline | Baseline mean Peak systolic velocity (PSV) in the Cavernosal arteries, on color Doppler examination, in the patient and control groups, before treatment. |
| Cavernosal Artery Mean PSV After Treatment | 2 weeks | Cavernosal artery mean peak systolic velocity (PSV) after treatment, on color Doppler examination, in the patient and control groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SHIM Score Before Treatment | Baseline | 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. |
| SHIM Score After Treatment | 1 month | 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. |
| Global Assessment Question (GAQ) | 1 month | 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. |
| EHS Before Treatment | Baseline | 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. 1. \- Penis is larger, but not hard. 2. \- Penis is hard, but not hard enough for penetration. 3. \- Penis is hard enough for penetration, but not completely hard. 4. \- Penis is completely hard and fully rigid. The average score is reported for each group. |
| SEP-Q2 Question After Treatment | 1 month | 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. |
| SEP-Q3 Question Before Treatment | Baseline | 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. |
| SEP-Q3 Question After Treatment | 1 month | 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. |
| SEP-Q2 Question Before Treatment | Baseline | 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?) |
| EHS After Treatment | 2 weeks | 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. 1. \- Penis is larger, but not hard. 2. \- Penis is hard, but not hard enough for penetration. 3. \- Penis is hard enough for penetration, but not completely hard. 4. \- Penis is completely hard and fully rigid. The average score is reported for each group. |
Countries
Egypt
Participant flow
Recruitment details
Started Nov 1, 2015 Completed May 24, 2016 Cairo University Andrology outpatient clinic
Participants by arm
| Arm | Count |
|---|---|
| (BTX) A Group 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.
Botulinum Toxin Type A: 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. | 12 |
| Saline Group 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.
Normal Saline: 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. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Saline Group | (BTX) A Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 23 Participants |
| Age, Continuous | 55.1 years | 52.1 years | 53.6 years |
| Gender Female | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 12 Participants | 12 Participants | 24 Participants |
| Region of Enrollment Egypt | 12 participants | 12 participants | 24 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (BTX) A | Cavernosal Artery Mean PSV After Treatment | 34.0 cm/s | Standard Deviation 9.32 |
| Saline Group | Cavernosal Artery Mean PSV After Treatment | 30.5 cm/s | Standard Deviation 16.4 |
Comparison: Comparing the mean PSV before \& after treatment in the study group using the t-test.p-value: 0.0049t-test, 1 sided
Comparison: Comparing the mean PSV before \& after treatment in the control group using the t-test.p-value: 0.68t-test, 1 sided
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (BTX) A | Cavernosal Artery Mean PSV Before Treatment | 24.5 cm/s | Standard Deviation 4.8 |
| Saline Group | Cavernosal Artery Mean PSV Before Treatment | 28.2 cm/s | Standard Deviation 9.79 |
Secondary
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. 1. \- Penis is larger, but not hard. 2. \- Penis is hard, but not hard enough for penetration. 3. \- Penis is hard enough for penetration, but not completely hard. 4. \- Penis is completely hard and fully rigid. The average score is reported for each group.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (BTX) A | EHS After Treatment | 2.75 units on EHS scale | Standard Deviation 0.622 |
| Saline Group | EHS After Treatment | 2.17 units on EHS scale | Standard Deviation 0.389 |
Comparison: Comparing the Erection hardness score before \& after treatment in the study group.p-value: 0.01086956Wilcoxon (Mann-Whitney)
Comparison: Comparing the Erection hardness score before \& after treatment in the control group.p-value: 0.6618176Wilcoxon (Mann-Whitney)
Secondary
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. 1. \- Penis is larger, but not hard. 2. \- Penis is hard, but not hard enough for penetration. 3. \- Penis is hard enough for penetration, but not completely hard. 4. \- Penis is completely hard and fully rigid. The average score is reported for each group.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (BTX) A | EHS Before Treatment | 2.08 units on EHS scale | Standard Deviation 0.515 |
| Saline Group | EHS Before Treatment | 2.17 units on EHS scale | Standard Deviation 0.577 |
Secondary
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.
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| (BTX) A | Global Assessment Question (GAQ) | 7 participants |
| Saline Group | Global Assessment Question (GAQ) | 1 participants |
p-value: 0.027191Fisher Exact
Secondary
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.
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| (BTX) A | SEP-Q2 Question After Treatment | 7 participants |
| Saline Group | SEP-Q2 Question After Treatment | 2 participants |
Comparison: Fisher Exact Test was used to compare the change in the number of in patients who answered Yes in Secondary Outcome 8 (SEP-Q2 Question Before Treatment) to patients who answered Yes in Secondary Outcome 9 (SEP-Q2 Question after Treatment), for both (BTXA) and Saline groups.p-value: 0.109091Fisher Exact
Secondary
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?)
Time frame: Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| (BTX) A | SEP-Q2 Question Before Treatment | 0 participants |
| Saline Group | SEP-Q2 Question Before Treatment | 2 participants |
Secondary
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.
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| (BTX) A | SEP-Q3 Question After Treatment | 3 participants |
| Saline Group | SEP-Q3 Question After Treatment | 1 participants |
Comparison: Fisher Exact Test was used to compare the change in patients who answered Yes in Secondary Outcome 10 (SEP-Q3 Question Before Treatment) to patients who answered Yes in Secondary Outcome 11 (SEP-Q3 Question after Treatment).p-value: 1Fisher Exact
Secondary
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.
Time frame: Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| (BTX) A | SEP-Q3 Question Before Treatment | 0 participants |
| Saline Group | SEP-Q3 Question Before Treatment | 0 participants |
Secondary
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.
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (BTX) A | SHIM Score After Treatment | 10.3 units on SHIM scale | Standard Deviation 5.38 |
| Saline Group | SHIM Score After Treatment | 6.67 units on SHIM scale | Standard Deviation 3.68 |
Comparison: SHIM Score in the study group before \& after treatment.p-value: 0.00751288Wilcoxon (Mann-Whitney)
Comparison: SHIM Score in the control group before \& after treatment.p-value: 0.6618176Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (BTX) A | SHIM Score Before Treatment | 5.58 units on the SHIM scale | Standard Deviation 1.93 |
| Saline Group | SHIM Score Before Treatment | 5.75 units on the SHIM scale | Standard Deviation 2.3 |