Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial

EBioMedicine. 2016 Jan 19;5:204-10. doi: 10.1016/j.ebiom.2016.01.024. eCollection 2016 Mar.

Abstract

Background: Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction.

Methods: Seventeen men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5-18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study is registered with ClinicalTrials.gov, NCT02240823.

Findings: Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered their erectile function and were able to accomplish sexual intercourse. Post-hoc stratification according to urinary continence status was performed. Accordingly, for continent men (median IIEFinclusion = 7 (95% CI 5-12), 8 out of 11 men recovered erectile function (IIEF6months = 17 (6-23)), corresponding to a mean difference of 0.57 (0.38-0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5-6); mean difference 1 (95% CI 0.85-1.18), p > 0.9999).

Interpretation: In this phase I trial a single intracavernosal injection of freshly isolated autologous ADRCs was a safe procedure. A potential efficacy is suggested by a significant improvement in IIEF-5 scores and erectile function. We suggest that ADRCs represent a promising interventional therapy of ED following prostatectomy.

Funding: Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society.

Keywords: ADRC, adipose-derived regenerative cells; Adipose-derived regenerative cells; Adipose-derived stem cells; Adipose-derived stromal vascular fraction; BMI, body mass index; CFU-F, fibroblastoid colony forming units; Cell therapy; Clinical trial; ED, erectile dysfunction; EHS, erection hardness score; Erectile dysfunction; ICIQ-UI SF, incontinence questionnaire – urinary incontinence – short form questionnaire; IIEF-5, international index of erectile function-5; LUTS, lower urinary tract symptoms; NSAID, nonsteroidal antiinflammatory drug; PDE-5, phosphodiesterase-5; RP, radical prostatectomy; SVF, stromal vascular fraction.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / transplantation
  • Aged
  • Cell Differentiation / genetics
  • Cell- and Tissue-Based Therapy*
  • Erectile Dysfunction / etiology
  • Erectile Dysfunction / physiopathology
  • Erectile Dysfunction / therapy*
  • Humans
  • Male
  • Middle Aged
  • Prostatectomy / adverse effects
  • Prostatic Neoplasms / complications
  • Prostatic Neoplasms / surgery
  • Prostatic Neoplasms / therapy*
  • Regenerative Medicine / methods
  • Stromal Cells / cytology
  • Stromal Cells / transplantation*

Associated data

  • ClinicalTrials.gov/NCT02240823