Botulinum Toxin for Erectile Dysfunction

• ClinicalTrials.gov Identifier: NCT03102762
• Recruitment Status: Completed
• First Posted: April 6, 2017
• Results First Posted: December 5, 2019
• Last Update Posted: January 7, 2020
• Sponsor: Cairo University
• Information provided by (Responsible Party): Hussein Ghanem, Cairo University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sexual Dysfunction; Erectile Dysfunction	Drug: Botulinum Toxin Type A; Drug: Normal saline	Phase 2; Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, randomized double blind placebo control ( RDBPC) study.
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Intracavernosal Injection of Botulinum Toxin Type A in the Treatment of Erectile Dysfunction (Phase 2 Study)
• Actual Study Start Date: January 3, 2017
• Actual Primary Completion Date: January 10, 2019
• Actual Study Completion Date: January 10, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Botulinum Toxin Type A (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.	Drug: 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.
Placebo Comparator: Placebo Group; 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; The treatment group will be injected with 1 ml normal saline one day following penile colour doppler assessment.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. SHIM Score Before Treatment [ Time Frame: 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.
2. SHIM Score After Treatment [ Time Frame: 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.

3. SHIM Score After Treatment [ Time Frame: 6 and 12 weeks after injection. ]

   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.

4. Penile Size Before Treatment [ Time Frame: Baseline ]

   Measurement of penile length before treatment:

   Flaccid, stretched and erect penile length.

5. Penile Size After Treatment [ Time Frame: 2 weeks after injection. ]
   Measurement of penile length after treatment.
6. Penile Size After Treatment [ Time Frame: 6 and 12 weeks after injection. ]
   Measurement of penile length after treatment.
7. Intra-vaginal Latency Time Before Treatment [ Time Frame: Baseline ]
   Measurement of the duration of intercourse from intromission to ejaculation before treatment.
8. Intra-vaginal Latency Time After Treatment [ Time Frame: 2 weeks after injection. ]
   Measurement of the duration of intercourse from intromission to ejaculation after treatment.
9. Intra-vaginal Latency Time After Treatment [ Time Frame: 6 and 12 weeks after injection. ]
   Measurement of the duration of intercourse from intromission to ejaculation after treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Egypt

Department of Andrology, Cairo University

Cairo, Egypt, 11231

Sponsors and Collaborators

Cairo University

Investigators

• Study Director: Islam M Fathy, MD; Cairo University
• Study Director: Abdelrahman A Hassan, Msc; Cairo University

  Study Documents (Full-Text)

Documents provided by Hussein Ghanem, Cairo University:

Study Protocol and Statistical Analysis Plan  [PDF] January 3, 2017

More Information

Additional Information:

Botulinum Toxin Type A and Erectile Dysfunction (Phase 1 study) 

Publications:

Ghanem H, Soliman I, AbdulHamid M, et. PS-08-016 Can intracavernosal botulinum toxin injection salvage vascular erectile dysfunction patients not responding to oral and intracavernous therapy? A pilot study. May 2016. Volume 13, Issue 5, Supplement 2, Page S116.

• Responsible Party: Hussein Ghanem, Professor, Cairo University
• ClinicalTrials.gov Identifier: NCT03102762
• Other Study ID Numbers: 1232017
• First Posted: April 6, 2017
• Results First Posted: December 5, 2019
• Last Update Posted: January 7, 2020
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Hussein Ghanem, Cairo University:

Erectile dysfunction; Botulinum toxin A; Botox

Additional relevant MeSH terms:

Erectile Dysfunction; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Mental Disorders; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents