Erectile Dysfunction, Sexual Dysfunction
Conditions
Keywords
Erectile dysfunction, Botulinum toxin A, Botox
Brief summary
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
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.
Interventions
DRUGBotulinum Toxin Type A
Drug: Botulinum Toxin Type A The treatment group will be injected with 100 units BTX-A one day following penile colour doppler assessment.
DRUGNormal saline
The treatment group will be injected with 1 ml normal saline one day following penile colour doppler assessment.
Sponsors
Cairo University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Intervention model description
Prospective, randomized double blind placebo control ( RDBPC) study.
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Right (PSV R) and Left (PSV L) 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. |
| Right (PSV R) and Left (PSV L) 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 |
|---|---|---|
| Penile Size Before Treatment | Baseline | Measurement of penile length before treatment: Flaccid, stretched and erect penile length. |
| Penile Size After Treatment | 2 weeks after injection. | Measurement of penile length after treatment. |
| 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. |
| Intra-vaginal Latency Time After Treatment | 2 weeks after injection. | Measurement of the duration of intercourse from intromission to ejaculation after treatment. |
| Intra-vaginal Latency Time Before Treatment | Baseline | Measurement of the duration of intercourse from intromission to ejaculation before treatment. |
| SHIM Score After Treatment | 2 weeks after injection. | 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. |
Countries
Egypt
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BTX-A Group Experimental: BTX-A Group The treatment group, 35 patients, will be injected with 100 units BTX-A one day following penile colour Doppler assessment.
Botulinum Toxin Type A: Drug: Botulinum Toxin Type A The treatment group will be injected with 100 units BTX-A one day following penile colour doppler assessment. | 35 |
| Placebo Group Saline Group:
The control group, 35 patients, will be injected with 1 ml normal saline one day following penile colour Doppler assessment.
Normal saline: The treatment group will be injected with 1 ml normal saline one day following penile colour doppler assessment. | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | BTX-A Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 32 Participants | 63 Participants |
| Age, Continuous | 54.26 years STANDARD_DEVIATION 7.8 | 56 years STANDARD_DEVIATION 9.12 | 55.13 years STANDARD_DEVIATION 8.47 |
| Race/Ethnicity, Customized Egyptian | 35 Participants | 35 Participants | 70 Participants |
| Region of Enrollment Egypt | 35 Participants | 35 Participants | 70 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 35 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
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.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX-A Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV After Treatment | PSV R | 45.68 cm/sec | Standard Deviation 13.27 |
| BTX-A Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV After Treatment | PSV L | 46.015 cm/sec | Standard Deviation 13.03 |
| Placebo Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV After Treatment | PSV R | 31.67 cm/sec | Standard Deviation 15.67 |
| Placebo Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV After Treatment | PSV L | 32.09 cm/sec | Standard Deviation 16.47 |
Primary
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.
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX-A Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV Before Treatment | PSV R | 34.52 cm/sec | Standard Deviation 12.15 |
| BTX-A Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV Before Treatment | PSV L | 34.33 cm/sec | Standard Deviation 11.21 |
| Placebo Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV Before Treatment | PSV R | 30.85 cm/sec | Standard Deviation 15.26 |
| Placebo Group | Right (PSV R) and Left (PSV L) Cavernosal Artery Mean PSV Before Treatment | PSV L | 31.73 cm/sec | Standard Deviation 15.97 |
Secondary
Intra-vaginal Latency Time After Treatment
Measurement of the duration of intercourse from intromission to ejaculation after treatment.
Time frame: 6 and 12 weeks after injection.
Population: One patient was dropped out from the treatment group after 2 weeks injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 6 weeks IVLT less than 1 minute | 9 Participants |
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 6 weeks IVLT between 1 to 3 minutes | 15 Participants |
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 6 weeks IVLT more than 3 minutes | 10 Participants |
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 12 weeks IVLT less than 1 minute | 9 Participants |
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 12 weeks IVLT between 1 to 3 minutes | 14 Participants |
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 12 weeks IVLT more than 3 minutes | 11 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 12 weeks IVLT between 1 to 3 minutes | 19 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 6 weeks IVLT less than 1 minute | 8 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 12 weeks IVLT less than 1 minute | 8 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 6 weeks IVLT between 1 to 3 minutes | 19 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 12 weeks IVLT more than 3 minutes | 8 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 6 weeks IVLT more than 3 minutes | 8 Participants |
Secondary
Intra-vaginal Latency Time After Treatment
Measurement of the duration of intercourse from intromission to ejaculation after treatment.
Time frame: 2 weeks after injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 2 weeks IVLT less than 1 minute | 12 Participants |
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 2 weeks IVLT between 1 to 3 minutes | 13 Participants |
| BTX-A Group | Intra-vaginal Latency Time After Treatment | After 2 weeks IVLT more than 3 minutes | 10 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 2 weeks IVLT less than 1 minute | 8 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 2 weeks IVLT between 1 to 3 minutes | 18 Participants |
| Placebo Group | Intra-vaginal Latency Time After Treatment | After 2 weeks IVLT more than 3 minutes | 9 Participants |
Secondary
Intra-vaginal Latency Time Before Treatment
Measurement of the duration of intercourse from intromission to ejaculation before treatment.
Time frame: Baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BTX-A Group | Intra-vaginal Latency Time Before Treatment | IVLT less than 1 minutes | 12 Participants |
| BTX-A Group | Intra-vaginal Latency Time Before Treatment | IVLT from 1 to 3 minutes | 13 Participants |
| BTX-A Group | Intra-vaginal Latency Time Before Treatment | IVLT more than 3 minutes | 10 Participants |
| Placebo Group | Intra-vaginal Latency Time Before Treatment | IVLT less than 1 minutes | 9 Participants |
| Placebo Group | Intra-vaginal Latency Time Before Treatment | IVLT from 1 to 3 minutes | 18 Participants |
| Placebo Group | Intra-vaginal Latency Time Before Treatment | IVLT more than 3 minutes | 8 Participants |
Secondary
Penile Size After Treatment
Measurement of penile length after treatment.
Time frame: 6 and 12 weeks after injection.
Population: One patient was dropped out from the treatment group after 2 weeks injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX-A Group | Penile Size After Treatment | After 6 weeks flaccid | 10.54 cm | Standard Deviation 1.83 |
| BTX-A Group | Penile Size After Treatment | After 6 weeks stretched | 13.46 cm | Standard Deviation 1.81 |
| BTX-A Group | Penile Size After Treatment | After 12 weeks flaccid | 10.46 cm | Standard Deviation 1.74 |
| BTX-A Group | Penile Size After Treatment | After 12 weeks stretched | 13.44 cm | Standard Deviation 1.79 |
| Placebo Group | Penile Size After Treatment | After 12 weeks stretched | 13.4 cm | Standard Deviation 2.58 |
| Placebo Group | Penile Size After Treatment | After 6 weeks flaccid | 10.99 cm | Standard Deviation 2.49 |
| Placebo Group | Penile Size After Treatment | After 12 weeks flaccid | 10.99 cm | Standard Deviation 2.49 |
| Placebo Group | Penile Size After Treatment | After 6 weeks stretched | 13.4 cm | Standard Deviation 2.58 |
Secondary
Penile Size After Treatment
Measurement of penile length after treatment.
Time frame: 2 weeks after injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX-A Group | Penile Size After Treatment | After 2 weeks flaccid | 10.46 cm | Standard Deviation 1.8 |
| BTX-A Group | Penile Size After Treatment | After 2 weeks stretched | 13.41 cm | Standard Deviation 1.78 |
| BTX-A Group | Penile Size After Treatment | After 2 weeks erect | 14.26 cm | Standard Deviation 1.66 |
| Placebo Group | Penile Size After Treatment | After 2 weeks flaccid | 11.01 cm | Standard Deviation 2.52 |
| Placebo Group | Penile Size After Treatment | After 2 weeks stretched | 13.4 cm | Standard Deviation 2.58 |
| Placebo Group | Penile Size After Treatment | After 2 weeks erect | 14.03 cm | Standard Deviation 2.57 |
Secondary
Penile Size Before Treatment
Measurement of penile length before treatment: Flaccid, stretched and erect penile length.
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX-A Group | Penile Size Before Treatment | Flaccid penile length | 10.17 cm | Standard Deviation 1.73 |
| BTX-A Group | Penile Size Before Treatment | Stretched penile length | 13.36 cm | Standard Deviation 1.8 |
| BTX-A Group | Penile Size Before Treatment | Erect penile length | 14.17 cm | Standard Deviation 1.72 |
| Placebo Group | Penile Size Before Treatment | Flaccid penile length | 10.99 cm | Standard Deviation 2.49 |
| Placebo Group | Penile Size Before Treatment | Stretched penile length | 13.4 cm | Standard Deviation 2.58 |
| Placebo Group | Penile Size Before Treatment | Erect penile length | 14.01 cm | Standard Deviation 2.56 |
Secondary
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.
Time frame: 6 and 12 weeks after injection.
Population: One patient was dropped out after 2 weeks of injection from the BTX-A Group
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX-A Group | SHIM Score After Treatment | 6 weeks after injection | 9.97 score on a scale | Standard Deviation 5.92 |
| BTX-A Group | SHIM Score After Treatment | 12 weeks after injection | 8.26 score on a scale | Standard Deviation 4.07 |
| Placebo Group | SHIM Score After Treatment | 6 weeks after injection | 5.77 score on a scale | Standard Deviation 1.82 |
| Placebo Group | SHIM Score After Treatment | 12 weeks after injection | 5.57 score on a scale | Standard Deviation 1.399 |
Secondary
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.
Time frame: 2 weeks after injection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTX-A Group | SHIM Score After Treatment | 6.66 score on a scale | Standard Deviation 2.17 |
| Placebo Group | SHIM Score After Treatment | 6.11 score on a scale | Standard Deviation 2.82 |
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 Group | SHIM Score Before Treatment | 5.4 score on a scale | Standard Deviation 1.67 |
| Placebo Group | SHIM Score Before Treatment | 5.69 score on a scale | Standard Deviation 1.08 |