Erectile Dysfunction Following Radical Prostatectomy, Erectile Dysfunction
Conditions
Keywords
Radical Prostatectomy, Erectile Dysfunction, Penile Rehabilitation, Nerve-Sparing Surgery, PRP, Male Urogenital Diseases, Platelet-rich plasma
Brief summary
This study will test whether injections of platelet-rich plasma (PRP) can improve erectile function in men with persistent erectile dysfunction (ED) at least 12 months after nerve-sparing radical prostatectomy for prostate cancer. Participants will be randomly assigned to receive either two PRP injections or two saline (placebo) injections into the penis, administered one month apart in a double-blind fashion. Erectile function will be assessed using the International Index of Erectile Function (IIEF) questionnaire at baseline and at 1, 3, 6, and 12 months after the last injection. The primary objective is to determine whether PRP improves the erectile function domain of the IIEF more than saline at one month after the last injection
Detailed description
Erectile dysfunction is common after nerve-sparing radical prostatectomy and may persist despite recovery from the initial nerve injury. Platelet-rich plasma (PRP) is prepared from autologous blood and contains growth factors that may promote angiogenesis and tissue regeneration. Preclinical studies suggest that PRP may improve erectile function after cavernous nerve injury, but PRP remains an experimental treatment, and no published study has specifically evaluated its effect in men with erectile dysfunction following radical prostatectomy. The hypothesis is that intracavernosal PRP injections improve erectile function more than saline injections in men with erectile dysfunction persisting 1-3 years after nerve-sparing radical prostatectomy. Eligible participants will be stratified according to unilateral or bilateral nerve-sparing surgery and randomized 1:1 to receive two intracavernosal injections of either autologous PRP or saline, administered one month apart. An unblinded team member who has no direct interaction with participants will prepare the injections. The participant and the physician administering the injection will remain blinded to treatment allocation. Syringes will be covered with opaque material to maintain blinding. Blood will be collected before each injection in all participants. For participants assigned to PRP, the blood will be used to prepare the treatment. For the first 10 participants assigned to saline, PRP will also be prepared and analysed to verify the platelet concentration achieved with the preparation procedure. Blood collected from the remaining participants assigned to saline will be discarded. Participants must discontinue other treatments for erectile dysfunction for four weeks before baseline and until the assessment one month after the last injection. Thereafter, other treatments for erectile dysfunction will be permitted and recorded. Erectile function and other study outcomes will be assessed at baseline and at 1, 3, 6, and 12 months after the last injection. The primary outcome is the between-group difference in change from baseline in the erectile function domain of the International Index of Erectile Function at one month after the last injection.
Interventions
A volume of 5 mL PRP will be administered in corpus cavernosum on two occasions, with a 1-month interval between injections
A volume of 5 mL saline solution will be administered in corpus cavernosum on two occasions, with a 1-month interval between injections.
Sponsors
Herlev and Gentofte Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 40-75 years * Underwent unilateral or bilateral nerve-sparing radical prostatectomy between 1 and 3 years prior to the study * Good erectile function prior to surgery (IIEF-EF score ≥ 22) * Erectile dysfunction at inclusion with an IIEF-EF score \< 22 without aids * Acceptance of a pause in other treatments for erectile dysfunction from 4 weeks before baseline (wash-out) until the 1-month follow-up after the last injection * In a stable relationship lasting at least 6 months with a desire for sexual activity * Able to understand and accept the study protocol
Exclusion criteria
* Known psychiatric, neurological and/or endocrinological disease requiring medication (including hypogonadism with total testosterone \<12 nmol/l). * Severe urinary incontinence preventing sexual activity (assessed by a physician at inclusion) * Clinical or biochemical recurrence of prostate cancer * Other surgery or radiation therapy in the pelvic region * Severe cardiac disease in the form of unstable angina, NYHA class \>II heart failure, uncontrolled arrhythmia, or severe symptomatic and/or significant valvular disease * Use of anti-androgen medication * Peyronie's disease and/or previous episodes of priapism * Excessive alcohol consumption (more than 21 units per week)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in IIEF-EF score from baseline to 1 month after the final treatment session | From baseline to 1 month post the last intervention | Change in the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) from baseline to 1 month after the final treatment session. The change in IIEF-EF score will be compared between the PRP and saline groups using an intention-to-treat analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in IIEF-EF score at 1 month after the final treatment session - per-protocol analysis | From baseline to 1 month post the last intervention | Change in the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) from baseline to 1 month after the final treatment session. The change in IIEF-EF score will be compared between the PRP and saline groups using a per-protocol analysis. |
| Change in IIEF-EF score at 3, 6, and 12 months after the final treatment session | From baseline to 12 months post the last intervention | Change in the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) from baseline to 3, 6, and 12 months after the final treatment session. Analyses will be performed using both intention-to-treat and per-protocol populations, comparing the PRP and saline groups. |
| Analyses of participants achieving a clinically significant improvement in IIEF-EF score at 1, 3, 6, and 12 months | From baseline to 12 months post the last intervention | Intention-to-treat and per-protocol analyses of the proportion of participants achieving clinically significant improvements in IIEF-EF at 1, 3, 6, and 12 months following the final treatment session with PRP or saline. Clinically significant improvement is defined according to Rosen et al. as an increase of 2 points for mild ED, 5 points for moderate ED, and 7 points for severe ED |
| Change in IIEF domain scores at 1, 3, 6, and 12 months | From baseline to 12 months post the last intervention | Changes in the remaining domains of the International Index of Erectile Function (IIEF): orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. As no minimum clinically important difference has been established for these domains, changes in domain scores will be analysed as continuous variables and compared between the PRP and saline groups. |
| Participant satisfaction after treatment | From baseline to 12 months post last intervention | Subjective participant satisfaction following treatment, assessed using the Global Satisfaction Question. This analysis will be performed according to the intention-to-treat principle. |
| Use of additional treatments for erectile dysfunction | Until 12 months post last intervention. | Use of additional treatments for erectile dysfunction during the study period, including oral medication, intraurethral treatment, intracavernosal injections, vacuum erection devices, and penile implants. The use of additional treatments will be compared between the PRP and saline groups. |
| Treatment effect according to baseline severity of erectile dysfunction | From baseline to 12 months post last intervention | Subgroup analyses of treatment effects according to severity of erectile dysfunction at baseline (recorded just before the first injection). These analyses will be considered exploratory and hypothesis-generating. |
| Adverse events following treatment | From baseline to 12 months post last intervention | Incidence and type of adverse events following PRP and saline injections during the study period. All adverse events will be recorded and described in the final study manuscript. |
Countries
Denmark
Contacts
CONTACTFrederikke Bay Toft, MD
PRINCIPAL_INVESTIGATORMikkel Fode, MD, PhD
Herlev and Gentofte Hospital
Outcome results
None listed