Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study

Katsuhisa Yamada; Maeda Kenichiro; Yoichi M Ito; Fujio Inage; Toshiyuki Isoe; Nozomi Yokota; Osamu Sugita; Norihiro Sato; Khin Khin Tha; Norimasa Iwasaki; Teruyo Arato; Hideki Sudo

doi:10.1016/j.conctc.2021.100805

Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study

Contemp Clin Trials Commun. 2021 Jun 29:23:100805. doi: 10.1016/j.conctc.2021.100805. eCollection 2021 Sep.

Authors

Katsuhisa Yamada^{1

2}, Maeda Kenichiro³, Yoichi M Ito⁴, Fujio Inage³, Toshiyuki Isoe³, Nozomi Yokota³, Osamu Sugita³, Norihiro Sato³, Khin Khin Tha⁵, Norimasa Iwasaki^{1

2}, Teruyo Arato³, Hideki Sudo^{1

6}

Affiliations

¹ Department of Orthopaedic Surgery, Hokkaido University Hospital, N14W5, Sapporo, Japan.
² Department of Orthopaedic Surgery, Faculty of Medicine, and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo, Hokkaido, 060-8638, Japan.
³ Clinical Research and Medical Innovation Center, Hokkaido University Hospital, N14W5, Sapporo, Japan.
⁴ Department of Biostatistics, Hokkaido University Graduate School of Medicine, N14W5, Sapporo, Hokkaido, Japan.
⁵ Department of Diagnostic Imaging, Hokkaido University Hospital, N14W5, Sapporo, Hokkaido, Japan.
⁶ Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan.

Abstract

Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.

Keywords: First-in-human pilot study; Intervertebral disc herniation; Ultra-purified alginate gel.