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 Urology

Study Protocol

Masaaki Mizuno¹  Yachiyo Kuwatsuka¹  Shinobu Shimizu¹  Akihiro Hirakawa²  Shinobu Nakayama³  Kazutaka Narimoto⁴  Yuzuru Kamei⁵  Keisuke Takanari⁵  Kazuhiro Toriyama⁶  Tomonori Yamanishi⁷  Yoshihisa Matsukawa⁸  Yasuhito Funahashi⁸  Tokunori Yamamoto⁸  Momokazu Gotoh⁸  Osamu Ishizuka⁹ 

[1] Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, 466-8560, Nagoya, Aichi, Japan;Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, 466-8560, Nagoya, Aichi, Japan;Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan;Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, 466-8560, Nagoya, Aichi, Japan;Department of Clinical Research Management, Clinical Research Center, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-ku, Aichi 460-0001, Nagoya, Japan;Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, 920-8640, Kanazawa, Ishikawa, Japan;Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Aichi, Japan;Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Aichi, Japan;Department of Plastic and Reconstructive Surgery, Nagoya City University Hospital, 1-Kawasumi, Mizuho-cho, Mizuho-ku, 467-8602, Nagoya, Aichi, Japan;Department of Urology, Continence Center, Dokkyo Medical University, 880 Kita-Kobayashi, Mibu-machi, Shimotsuga-gun, 321-0293, Tochigi, Japan;Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Aichi, Japan;Department of Urology, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621, Matsumoto, Japan;

关键词: Stress urinary incontinence;    Lower urinary tract symptoms;    Regenerative medicine;    Cell therapy;    Prostatectomy;    Adipose-derived regenerative cells;   

DOI  :  10.1186/s12894-017-0282-7

 received in 2016-08-05, accepted in 2017-09-20,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMale 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.MethodsThe 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%.DiscussionThe 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.Trial registrationThis trial was registered at the University Hospital Medical information Network Clinical Trial Registry (UMIN-CTR Unique ID: UMIN000017901; Registered July 1, 2015) and at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02529865; Registered August 18, 2015).

【 授权许可】

CC BY   
© The Author(s). 2017