Evaluating the impact of adjunctive istradefylline on the cumulative dose of levodopa-containing medications in Parkinson’s disease: study protocol for the ISTRA ADJUST PD randomized, controlled study
Taku Hatano,
Osamu Kano,
Renpei Sengoku,
Asako Yoritaka,
Keisuke Suzuki,
Noriko Nishikawa,
Yohei Mukai,
Kyoichi Nomura,
Norihito Yoshida,
Morinobu Seki,
Miho Kawabe Matsukawa,
Hiroo Terashi,
Katsuo Kimura,
Jun Tashiro,
Shigeki Hirano,
Hidetomo Murakami,
Hideto Joki,
Tsuyoshi Uchiyama,
Hideki Shimura,
Kotaro Ogaki,
Jiro Fukae,
Yoshio Tsuboi,
Kazushi Takahashi,
Toshimasa Yamamoto,
Naotake Yanagisawa,
Hiroshi Nagayama
Affiliations
Taku Hatano
Department of Neurology, Faculty of Medicine, Juntendo University
Osamu Kano
Department of Neurology, Faculty of Medicine, Toho University
Renpei Sengoku
Department of Neurology, Jikei University Daisan Hospital
Asako Yoritaka
Department of Neurology, Juntendo University Koshigaya Hospital
Keisuke Suzuki
Department of Neurology, Dokkyo Medical University Hospital
Noriko Nishikawa
Department of Neurology, Faculty of Medicine, Juntendo University
Yohei Mukai
Department of Neurology, National Center of Neurology and Psychiatry
Kyoichi Nomura
Department of Neurology, Saitama Medical Center
Norihito Yoshida
Department of Neurology, Saitama Medical Center
Morinobu Seki
Department of Neurology, Keio University School of Medicine
Miho Kawabe Matsukawa
Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
Hiroo Terashi
Department of Neurology, Tokyo Medical University Hospital
Katsuo Kimura
Department of Neurology, Yokohama City University Medical Center
Jun Tashiro
Sapporo Parkinson MS Neurological Clinic
Shigeki Hirano
Department of Neurology, Graduate School of Medicine, Chiba University
Hidetomo Murakami
Department of Neurology, The Jikei University Hospital
Hideto Joki
Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine
Tsuyoshi Uchiyama
Department of Neurology, Seirei Hamamatsu General Hospital
Hideki Shimura
Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center
Kotaro Ogaki
Department of Neurology, Juntendo University Urayasu Hospital
Jiro Fukae
Department of Neurology, Juntendo University Nerima Hospital
Yoshio Tsuboi
Department of Neurology, Fukuoka University School of Medicine
Kazushi Takahashi
Department of Neurology, Tokyo Metropolitan Neurological Hospital
Toshimasa Yamamoto
Department of Neurology, Saitama Medical University Hospital, Saitama Medical University
Naotake Yanagisawa
Medical Technology Innovation Center, Juntendo University and Juntendo Clinical Research and Trial Center
Abstract Background Levodopa remains the most effective symptomatic treatment for Parkinson’s disease (PD) more than 50 years after its clinical introduction. However, the onset of motor complications can limit pharmacological intervention with levodopa, which can be a challenge when treating PD patients. Clinical data suggest using the lowest possible levodopa dose to balance the risk/benefit. Istradefylline, an adenosine A2A receptor antagonist indicated as an adjunctive treatment to levodopa-containing preparations in PD patients experiencing wearing off, is currently available in Japan and the US. Preclinical and preliminary clinical data suggested that adjunctive istradefylline may provide sustained antiparkinsonian benefits without a levodopa dose increase; however, available data on the impact of istradefylline on levodopa dose titration are limited. The ISTRA ADJUST PD study will evaluate the effect of adjunctive istradefylline on levodopa dosage titration in PD patients. Methods This 37-week, multicenter, randomized, open-label, parallel-group controlled study in PD patients aged 30–84 years who are experiencing the wearing-off phenomenon despite receiving levodopa-containing medications ≥ 3 times daily (daily dose 300–400 mg) began in February 2019 and will continue until February 2022. Enrollment is planned to attain 100 evaluable patients for the efficacy analyses. Patients will receive adjunctive istradefylline (20 mg/day, increasing to 40 mg/day) or the control in a 1:1 ratio, stratified by age, levodopa equivalent dose, and presence/absence of dyskinesia. During the study, the levodopa dose will be increased according to symptom severity. The primary study endpoint is the comparison of the cumulative additional dose of levodopa-containing medications during the treatment period between the adjunctive istradefylline and control groups. Secondary endpoints include changes in efficacy rating scales and safety outcomes. Discussion This study aims to clarify whether adjunctive istradefylline can reduce the cumulative additional dose of levodopa-containing medications in PD patients experiencing the wearing-off phenomenon, and lower the risk of levodopa-associated complications. It is anticipated that data from ISTRA ADJUST PD will help inform future clinical decision-making for patients with PD in the real-world setting. Trial registration Japan Registry of Clinical Trials, jRCTs031180248 ; registered 12 March 2019.
