Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 3;22(1):71.
doi: 10.1186/s12883-022-02600-w.

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  1 , Osamu Kano  2 , Renpei Sengoku  3 , Asako Yoritaka  4 , Keisuke Suzuki  5 , Noriko Nishikawa  6   7 , Yohei Mukai  7 , Kyoichi Nomura  8 , Norihito Yoshida  8 , Morinobu Seki  9 , Miho Kawabe Matsukawa  10 , Hiroo Terashi  11 , Katsuo Kimura  12 , Jun Tashiro  13 , Shigeki Hirano  14 , Hidetomo Murakami  15 , Hideto Joki  16 , Tsuyoshi Uchiyama  17 , Hideki Shimura  18 , Kotaro Ogaki  19 , Jiro Fukae  20 , Yoshio Tsuboi  21 , Kazushi Takahashi  22 , Toshimasa Yamamoto  23 , Naotake Yanagisawa  24 , Hiroshi Nagayama  25
Affiliations

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 et al. BMC Neurol. .

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.

Keywords: Adenosine A2A receptor antagonist; Istradefylline; Levodopa; Levodopa dose; Parkinson’s disease.

PubMed Disclaimer

Conflict of interest statement

This study is funded by Kyowa Kirin Co., Ltd., Tokyo, Japan (commercial organization). The funding organization has implemented a peer review process of the study protocol.

TH is an associate editor/member of the editorial board for BMC Neurology and reports receiving grants and honoraria or consultation fees from Kyowa Kirin Co., Ltd. during the conduct of the study.

OK reports grants and consultation fees from Kyowa Kirin Co., Ltd. during the conduct of the study.

RS is an associate editor/member of the editorial board for BMC Neurology and reports grants and consultation fees from Kyowa Kirin Co., Ltd. during the conduct of the study.

AY reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study; and reports grants from Eisai Co., Ltd. and Sumitomo Dainippon Pharma, outside the submitted work.

KS is an editorial board member of BMC Neurology, and reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

NN reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

YM reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

KN reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

NYo reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

MS reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study; and received a Takeda Japan Medical Affairs Funded Research Grant 2018, and grants from Kanae Foundation for the promotion of medical science, outside the submitted work.

MM reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

HT reports grants and personal fees from Kyowa Kirin Co., Ltd. during the conduct of the study.

KK reports grants and personal fees from Kyowa Kirin Co., Ltd. during the conduct of the study; and personal fees from Medtronic, Boston Scientific, Ono Pharmaceuticals Co., Ltd., Otsuka Pharmaceuticals Co., Ltd., AbbVie GK, Eisai Co., Ltd., Takeda Pharmaceuticals Co., Ltd., and Sumitomo Dainippon Pharma, and grants from Novartis AG, outside the submitted work.

JT reports grants and non-financial support from Kyowa Kirin Co., Ltd. during the conduct of the study; and personal fees and non-financial support from Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., and FP Pharmaceutical Corporation, and non-financial support from Eisai Co., Ltd. and AbbVie GK outside the submitted work.

SH reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study; and grants from Eli Lilly Japan K.K., and grants and lecture fees from Nihon Medi-Physics Co., Ltd. outside the submitted work.

HM reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

HJ reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

TU reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

HS reports grants and lecture fees from Kyowa Kirin Co., Ltd. during the conduct of the study.

KO reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

JF reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

YT reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

KT reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

TY reports grants from Kyowa Kirin Co., Ltd. during the conduct of the study.

NYa reports grants and consultant fees from Kyowa Kirin Co., Ltd. during the conduct of the study.

HN reports grants and consultant fees from Kyowa Kirin Co., Ltd. during the conduct of the study.

Figures

Fig. 1
Fig. 1
ISTRA ADJUST PD study design. W, week
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Cuenca L, Gil-Martinez AL, Cano-Fernandez L, Sanchez-Rodrigo C, Estrada C, Fernandez-Villalba E, et al. Parkinson’s disease: a short story of 200 years. Histol Histopathol. 2019;34(6):573–591. - PubMed
    1. Lang AE, Lozano AM. Parkinson’s disease First of two parts. N Engl J Med. 1998;339(15):1044–53. - PubMed
    1. Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020;27(1):27–42. - PubMed
    1. Fahn S. The medical treatment of Parkinson disease from James Parkinson to George Cotzias. Mov Disord. 2015;30(1):4–18. - PubMed
    1. Hornykiewicz O. A brief history of levodopa. J Neurol. 2010;257(Suppl 2):S249–S252. - PubMed

Publication types

-