Intracavernosal Exosomes vs. Rectal Ozone for Post-RARP Erectile Dysfunction

Erectile dysfunction (ED) remains a prevalent and distressing complication following robotic-assisted radical prostatectomy (RARP), primarily manifesting secondary to cavernous nerve neuropraxia, subsequent localized hypoxia, and fibrotic remodeling of the corpus cavernosum. While standard pharmacotherapies (e.g., PDE5 inhibitors) offer symptomatic relief, they fail to reverse the underlying endothelial and neural detriments.Recent preclinical and clinical data suggest that stem cell-derived therapies, particularly cell-free exosomes, exhibit significant proangiogenic and antifibrotic properties. Extracellular vesicles containing components of the stem cell secretome, such as microRNAs, facilitate endothelial cell proliferation and tissue repair. Conversely, systemic ozone therapy has been hypothesized to enhance oxygen delivery, upregulate antioxidant enzymes, and modulate inflammatory cascades, potentially mitigating post-surgical ischemia. In this trial, eligible post-RARP patients will be randomized (1:1) to receive either a targeted intracavernosal injection of urine-derived exosomes (USC-Exos) or a scheduled regimen of rectal ozone-oxygen mixture insufflation. Erectile capacity, penile vascular hemodynamics (assessed via pharmacopenile duplex ultrasonography), and general health status will be prospectively monitored at baseline, 3, and 6 months post-intervention.

• Urine-Derived Exosomes (USC-Exos) (Biological): A single (or protocol-specified sequenced) bilateral intracavernosal injection of a sterile, cell-free urine-derived exosome suspension (e.g., 2 cc) into the corpus cavernosum, performed under clinical setting conditions.
• Rectal Medical Ozone Insufflation (Procedure): Administration of a standardized medical ozone and oxygen gas mixture (e.g., 30-40 µg/mL concentration) via rectal insufflation. The treatment will be administered for a predetermined number of sessions (e.g., 10 sessions spanning over 5 weeks) using a certified medical ozone generator.
• Daily Phosphodiesterase type 5 (PDE5) Inhibitor (Drug): Oral administration of a daily low-dose PDE5 inhibitor (e.g., Tadalafil 5 mg once daily) for a continuous duration of 6 months, aligning with standard clinical guidelines for post-operative erectile dysfunction management.

Primary outcomes

• Mean Change in International Index of Erectile Function (IIEF-5) Score [Baseline, 3 Months Post-Intervention, and 6 Months Post-Intervention.]: The International Index of Erectile Function (IIEF-5) is a validated self-reporting psychometric instrument utilized to assess erectile function severity. The total score ranges from a minimum of 5 to a maximum of 25. Higher scores represent better erectile function (a better outcome), with scores ≤21 indicating varying degrees of erectile dysfunction and 22-25 representing normal erectile function.

Secondary outcomes

• Change in Peak Systolic Velocity (PSV) [Baseline and 6 Months Post-Intervention.]: Objective measurement of cavernous arterial competence following an intracavernosal injection of a vasoactive agent, assessed via Pharmacopenile Duplex Ultrasonography (PPDU). Reported in centimeters per second (cm/s).
• Change in End-Diastolic Velocity (EDV) [Baseline and 6 Months Post-Intervention.]: Objective measurement of the cavernous veno-occlusive mechanism following an intracavernosal injection of a vasoactive agent, assessed via Pharmacopenile Duplex Ultrasonography (PPDU). Reported in centimeters per second (cm/s).
• Change in Resistive Index (RI) [Baseline and 6 Months Post-Intervention.]: Calculated ratio based on the peak systolic and end-diastolic velocities, used to evaluate penile vascular resistance via Pharmacopenile Duplex Ultrasonography (PPDU). It is reported as a unitless ratio.

Sex: Male, ages: 45 Years to 75 Years

Inclusion Criteria:

* History of Robotic-Assisted Radical Prostatectomy (ns-RARP) for localized prostate cancer.
* Normal preoperative erectile function (retrospective IIEF-5 score > 21).
* Presence of a stable, sexually active heterosexual relationship.
* Inadequate response or intolerance to maximum dose, on-demand oral Phosphodiesterase type 5 inhibitors (PDE5i).

Exclusion Criteria:

* History of adjuvant or salvage pelvic radiotherapy / androgen deprivation therapy (ADT).
* Presence of severe anatomical penile deformities (e.g., active phase Peyronie's disease).
* Uncontrolled endocrinological (e.g., HbA1c > 8.5%) or cardiovascular comorbidities.
* History of major cardiovascular events (myocardial infarction, stroke) within the preceding 6 months.
* Current use of systemic anticoagulants (excluding low-dose prophylactic aspirin).
* Concomitant use of any intraurethral alprostadil, vacuum erection devices (VED), or testosterone replacement therapy during the study period.