UROLOGIC

Clinical Studies

TITLE: “Concomitant Transurethral and Transvaginal-Periurethral Injection of Autologous Adipose Derived Stem Cells for Treatment of Female Stress Urinary Incontinence: A Phase One Clinical Trial”

SOURCE: Arjmand B, Safavi M, Heidari R, Aghayan H, T Bazargani S, Dehghani S, Goodarzi P, Mohammadi-Jahani F, Heidari F, Payab M, Pourmand G. Concomitant Transurethral and Transvaginal-Periurethral Injection of Autologous Adipose Derived Stem Cells for Treatment of Female Stress Urinary Incontinence: A Phase One Clinical Trial. Acta Med Iran. 2017 Jun;55(6):368-374.

SUMMARY: Stress urinary incontinence is a common medical problem among women. The urethral closure complex and/or the supportive mechanisms are responsible for incontinence in the majority of patients. Several surgical procedures with different degrees of invasiveness and outcomes have been reported to treat the problem. Although most of these procedures are reasonably effective, a general trend towards the study of natural and biocompatible tissues is emerging over popular synthetic materials. Here we report our experience of autologous adipose-derived stem cells transplantation into the periurethral region as a new method of stress urinary incontinence treatment. Ten women with symptoms of stress urinary incontinence were treated by injections of autologous adipose-derived stem cells into the periurethral region via transurethral and transvaginal approach under urethroscopic observation. This report presents the short-term outcome of the patients. The outcome measured by pad test results, ICIQ-SF scores, and Qmax. The mean age of the participants was 45.8±8.7 years. Urinary incontinence significantly decreased through the first two, 6 and 24 weeks after the injection therapy. The difference was significant in pad test results (P<0.001) and ICIQ-SF scores (P<0.001), especially comparing results between 2 and 6 weeks and among 6 and 24 weeks, but not for 2 and 6 weeks compared to each other. Surprisingly, Qmax showed improvement after the study period (means 32.6 vs. 35.7; P=0.002). This study showed that injection of the autologous adipose-derived stem cells to the periurethral region is a safe, yet short-term effective treatment option for stress urinary incontinence. Further studies with longer follow up are needed to confirm its long term efficacy.

PUBLIC DOWNLOAD OF FULL MANUSCRIPT: Arjmand 2017 PDF


TITLE: “Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study”

SOURCE: Choi JY, Kim TH, Yang JD, Suh JS, Kwon TG. Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study. Yonsei Med J. 2016 Sep;57(5):1152-8.

SUMMARY: After providing written informed consent, six men with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from the patients by liposuction. ADRCs were obtained by separation with centrifugation using the Celution cell-processing device. A mixture of ADRCs and adipose tissue were transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed using a 24-h pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) during 12-week follow-up. Urine leakage volume was improved with time in all patients in the 24-h pad test, with the exemption of temporal deterioration at the first 2 weeks post-injection in 2 patients. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 44.0 to 63.5 cm H₂O at 12 weeks after injection. MRI showed an increase in functional urethral length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were not observed in any case during follow-up. This study demonstrated that transurethral injection of autologous ADRCs can be a safe and effective treatment modality for postprostatectomy incontinence.

PUBLIC DOWNLOAD OF FULL MANUSCRIPT: Choi 2016 PDF


TITLE: “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”

SOURCE: Haahr MK, Jensen CH, Toyserkani NM, Andersen DC, Damkier P, Sørensen JA, Lund L, Sheikh SP. 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.

SUMMARY: 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. 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). 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.

PUBLIC DOWNLOAD OF FULL MANUSCRIPT: Haahr 2016 PDF


TITLE: “Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol”

SOURCE: Shimizu S, Yamamoto T, Nakayama S, Hirakawa A, Kuwatsuka Y, Funahashi Y, Matsukawa Y, Takanari K, Toriyama K, Kamei Y, Narimoto K, Yamanishi T, Ishizuka O, Mizuno M, Gotoh M. Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol. BMC Urol. 2017 Sep 25;17(1):89.

SUMMARY: Male stress urinary incontinence is a prevalent condition after radical prostatectomy. While the standard recommendation for the management of urine leakage is pelvic floor muscle training, its efficacy is still unsatisfactory. Therefore, we have focused on regenerative therapy, which consists of administering a periurethral injection of autologous regenerative cells from adipose tissue, separated using the Celution® system. Based on an interim data analysis of our exploratory study, we confirmed the efficacy and acceptable safety profile of this treatment. Accordingly, we began discussions with Japanese regulatory authorities regarding the development of this therapy in Japan. The Ministry of Health, Labour and Welfare suggested that we implement a clinical trial of a new medical device based on the Pharmaceutical Affaires Act in Japan. Next, we discussed the design of this investigator-initiated clinical trial (the ADRESU study) aimed at evaluating the efficacy and safety of this therapy, in a consultation meeting with the Pharmaceuticals and Medical Device Agency. The ADRESU study is an open-label, multi-center, single-arm study involving a total of 45 male stress urinary incontinence patients with mild-to-moderate urine leakage persisting more than 1 year after prostatectomy, in spite of behavioral and pharmacological therapies. The primary endpoint is the rate of patients at 52 weeks with improvement of urine leakage volume defined as a reduction from baseline greater than 50% by 24-h pad test. Our specific hypothesis is that the primary endpoint result will be higher than a pre-specified threshold of 10%. The ADRESU study is the first clinical trial of regenerative treatment for stress urinary incontinence by adipose-derived regenerative cells using the Celution® system based on the Japanese Pharmaceutical Affaires Act. We will evaluate the efficacy and safety in this trial to provide an adequate basis for marketing approval with the final objective of making this novel therapy widely available for Japanese patients.

PUBLIC DOWNLOAD OF FULL MANUSCRIPT: Shimizu 2017 PDF