Erythropoietin to Enhance Recovery of Erectile Function in Men Following Radical Prostatectomy

Study Overview
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Brief Summary
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This research study aims to explore the effectiveness of human erythropoietin versus placebo in promoting the recovery of erectile function in patients undergoing bilateral nerve-sparing radical retropubic prostatectomy for clinically localized prostate cancer. Pre-clinical studies have shown erythropoietin potently promoted recovery of erectile function in rats and humans have similar receptors on penile tissues and the periprostatic neurovascular bundles. A clinical non-randomized study conducted in men undergoing radical prostatectomy demonstrated a benefit to recovery of erectile function. Therefore, the hypothesis is that erythropoietin offers nerve protection in men undergoing nerve-sparing radical prostatectomy and results in a reduced degree of erectile dysfunction and also an improved rate of erection recovery following surgery.

Detailed Description
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This study will evaluate the effectiveness of erythropoietin versus placebo in the recovery of erectile function in patients undergoing bilateral nerve-sparing radical prostatectomy for prostate cancer. Recent laboratory findings in rat models and on human urogenital tissues suggest that erythropoietin may play a role in protection of the cavernous nerves during surgery. Some degree of nerve trauma occurs during bilateral nerve-sparing radical prostatectomy, but for most it is temporary. Erythropoietin will be studied as an investigational drug for enhancement of erectile function postoperatively in a prospective, randomized study. Erythropoietin has been used in many men undergoing open radical prostatectomy in the past according to FDA indications for preparation for noncardiac, nonvascular surgery with a high risk of blood loss. Evidence also suggests it is safe with no demonstration of increased risk of venous thromboembolism (blood clots) or cardiac events for men with prostate cancer undergoing radical prostatectomy. The length of the study is 12 months and involves receiving a dose of study drug or placebo on the day before surgery, the day of surgery, and the day following surgery. The dose is given by subcutaneous injection. The study will also require the completion of questionnaires which will be completed online every three months until study completion (at 3, 6, 9, and 12 months) to assess outcomes.

Official Title
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Erythropoietin to Enhance Recovery of Erectile Function in Men Following Radical Prostatectomy: a Prospective Randomized Controlled Trial (ERECT)

Conditions
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Prostate Cancer, Erectile Dysfunction

Intervention / Treatment
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* Drug: Placebo
* Drug: Erythropoietin (EPO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient eligibility consists of men 40 to 65 years of age Localized prostate cancer clinical stage T2a or lower Gleason grade of 3+4 or 3+3 prostate specific antigen (PSA) < 10 Scheduled to undergo curative prostatectomy applying bilateral nerve-sparing procedure, with intact pre-surgical erectile function International Index of Erectile Function-5 (IIEF-5) score of 22-25. The patient has a sexual partner, of at least 6 months. The patient's pre-surgical hematocrit is ≤ 48. The patient is willing to attempt intercourse at least 5 times per month following recovery from surgery. Exclusion Criteria: The patient has known penile deformity or a history of Peyronie's disease. The patient has planned pre or post operative androgen therapy. The patient has planned pre or post operative radiation therapy. The patient is on anticoagulation therapy. The patient has a history of sickle cell anemia. The patient has a history of high or low blood pressure that is not controlled. The patient is taking medications called nitrates The patient has a history of heart problems such as angina, heart failure, irregular heartbeats, or myocardial infarction The patient has a history of history of drug or alcohol abuse. The patient currently smokes or has a 20 pack/year history of cigarette smoking. The patient has a history of acute or chronic depression The patient has a history liver problems, or kidney problems. The patient has a history of retinitis pigmentosa or severe vision loss, including a condition called NAION, Nonarteritic Anterior Ischemic Optic Neuropathy. The patient has a history of spinal trauma or surgery to the brain or spinal cord. The patient has contraindications to the use of phosphodiesterase type 5 (PDE 5) inhibitors. Patient is currently participating in another clinical investigation that would serve as a contraindication to administering erythropoietin.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erythropoietin (EPO)<br>20,000 units of EPO given on the day before surgery, the day of surgery, and the day after surgery. | Drug: Erythropoietin (EPO)<br>* Erythropoietin (EPO)-induced Protein 29, Human; 20,000 units subcutaneously given the day before surgery, day of surgery, and the day after surgery.<br>|
| Placebo Comparator: Placebo<br>Placebo doses given the day before surgery, the day of surgery, and the day after surgery. | Drug: Placebo<br>* Saline injection (solution prepared by research pharmacy) subcutaneously given the day before surgery, day of surgery, and the day after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erectile Function as Assessed by the International Index of Erectile Function (IIEF) Questionnaire Erectile Function Domain | Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function. | At 6 months post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erectile Function as Assessed by the IIEF Questionnaire Erectile Function Domain | Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function. | At 3 months post-surgery | 
| Erectile Function as Assessed by the IIEF Questionnaire Erectile Function Domain | Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function. | At 9 months post-surgery | 
| Erectile Function as Assessed by the IIEF Questionnaire Erectile Function Domain | Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function. | At 12 months post-surgery | 
| Patient Score on the Overall IIEF Questionnaire | Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function. | At 3 months post-surgery | 
| Patient Score on the Overall IIEF Questionnaire | Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function. | At 6 months post-surgery | 
| Patient Score on the Overall IIEF Questionnaire | Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function. | At 9 months post-surgery | 
| Patient Score on the Overall IIEF Questionnaire | Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function. | At 12 months post-surgery | 
| Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS) | Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health. | At 3 months post-surgery | 
| Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS) | Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health. | At 6 months post-surgery | 
| Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS) | Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health. | At 9 months post-surgery | 
| Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS) | Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health. | At 12 months post-surgery | 
| Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain | Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100. | At 3 months post-surgery | 
| Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain | Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100. | At 6 months post-surgery | 
| Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain | Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100. | At 9 months post-surgery | 
| Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain | Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100. | At 12 months post-surgery | 
| Patient Score on the Quality of Erection Questionnaire (QEQ) | Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality. | At 3 months post-surgery | 
| Patient Score on the Quality of Erection Questionnaire (QEQ) | Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality. | At 6 months post-surgery | 
| Patient Score on the Quality of Erection Questionnaire (QEQ) | Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality. | At 9 months post-surgery | 
| Patient Score on the Quality of Erection Questionnaire (QEQ) | Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality. | At 12 months post-surgery | 
| Hemoglobin Level at 2 Weeks After Surgery | Hemoglobin level at 2 weeks after surgery in grams per deciliter (g/dl). | 2 weeks after surgery | 
| Number of Participants Requiring Transfusion During Hospitalization | Assess the number of participants requiring transfusion during hospitalization. | During hospital stay, up to 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erythropoietin, Radical Prostatectomy, Erectile Dysfunction, Prostate Cancer