A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY-PD III)

被引:53
作者
Biglan, Kevin M. [1 ,2 ]
Oakes, David [3 ]
Lang, Anthony E. [4 ,5 ]
Hauser, Robert A. [6 ]
Hodgeman, Karen [2 ]
Greco, Brittany [2 ]
Lowell, Jillian [1 ]
Rockhill, Rebecca [2 ]
Shoulson, Ira [7 ,8 ]
Venuto, Charles [2 ]
Young, Diony [9 ]
Simuni, Tanya [10 ]
机构
[1] Univ Rochester, Dept Neurol, Rochester, NY USA
[2] Univ Rochester, Ctr Human Expt Therapeut, Rochester, NY USA
[3] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA
[4] Univ Toronto, Toronto Western Hosp, Univ Hlth Network, Morton & Gloria Shulman Movement Disorder Unit, Toronto, ON, Canada
[5] Univ Toronto, Toronto Western Hosp, Univ Hlth Network,Dept Med, Edmond J Safra Parkinson Dis Program,Neurol Div, Toronto, ON, Canada
[6] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA
[7] Georgetown Univ, Dept Neurol, Washington, DC USA
[8] Georgetown Univ, Program Regulatory Sci & Med, Washington, DC USA
[9] Parkinson Dis Fdn, New York, NY USA
[10] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA
来源
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY | 2017年 / 4卷 / 06期
关键词
CALCIUM-CHANNEL BLOCKERS; QUALITY-OF-LIFE; EXPLORATORY-TRIALS; PROGRESSION; LEVODOPA; IMPACT; DISABILITY; ONSET; SCORE; RISK;
D O I
10.1002/acn3.412
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To describe the rationale for a novel study design and baseline characteristics of a disease-modifying trial of isradipine 10 mg daily in early Parkinson disease (PD). Methods: STEADY-PDIII is a 36-month, Phase 3, parallel group, placebo-controlled study of the efficacy of isradipine 10 mg daily in 336 participants with early PD as measured by the change in the Unified Parkinson Disease Rating Scale (UPDRS) Part I-III score in the practically defined ON state. Secondary outcome measures include clinically meaningful measures of disability progression in early PD: (1) Time to initiation and utilization of dopaminergic therapy; (2) Time to onset of motor complications; (3) Change in nonmotor disability. Exploratory measures include global measures of functional disability, quality of life, change in the ambulatory capacity, cognitive function, and pharmacokinetic analysis. Rationale for the current design and alternative design approaches are discussed. Results: The entire cohort of 336 participants was enrolled at 55 Parkinson Study Group sites in North America. The percentage of male participants were 68.5% with a mean age of 61.9 years (sd 9.0), mean Hoehn and Yahr stage of 1.7 (sd 0.5), mean UPDRS total of 23.1 (sd 8.6), and MoCA of 28.1 (sd 1.4). Interpretation: STEADY-PD III has a novel and innovative design allowing for the determination of longer duration benefits on clinically relevant outcomes in a relatively small cohort on top of the benefit derived from symptomatic therapy. Baseline characteristics are similar to those in previously enrolled de novo PD trials. This study represents a unique opportunity to evaluate the potential impact of a novel therapy to slow progression of PD disability and provide clinically meaningful benefits.
引用
收藏
页码:360 / 368
页数:9
相关论文
共 53 条
  • [1] Adams JL, 2016, MOV DISORD S2, V31
  • [2] Depression in Parkinson's disease - Must be properly diagnosis and treated to avoid serious morbidity
    Allain, H
    Schuck, S
    Mauduit, N
    [J]. BRITISH MEDICAL JOURNAL, 2000, 320 (7245) : 1287 - 1288
  • [3] Calcium channel blocking as a therapeutic strategy for Alzheimer's disease: The case for isradipine
    Anekonda, Thimmappa S.
    Quinn, Joseph F.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2011, 1812 (12): : 1584 - 1590
  • [4] [Anonymous], 1987, RECENT DEV PARKINSON
  • [5] The long-duration action of levodopa may be due to a postsynaptic effect
    Barbato, L
    Stocchi, F
    Monge, A
    Vacca, L
    Ruggieri, S
    Nordera, G
    Marsden, CD
    [J]. CLINICAL NEUROPHARMACOLOGY, 1997, 20 (05) : 394 - 401
  • [6] A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit
    Beal, M. Flint
    Oakes, David
    Shoulson, Ira
    Henchcliffe, Claire
    Galpern, Wendy R.
    Haas, Richard
    Juncos, Jorge L.
    Nutt, John G.
    Voss, Tiffini Smith
    Ravina, Bernard
    Shults, Clifford M.
    Helles, Karen
    Snively, Victoria
    Lew, Mark F.
    Griebner, Brian
    Watts, Arthur
    Gao, Shan
    Pourcher, Emmanuelle
    Bond, Louisette
    Kompoliti, Katie
    Agarwal, Pinky
    Sia, Cherissa
    Jog, Mandar
    Cole, Linda
    Sultana, Munira
    Kurlan, Roger
    Richard, Irene
    Deeley, Cheryl
    Waters, Cheryl H.
    Figueroa, Angel
    Arkun, Ani
    Brodsky, Matthew
    Ondo, William G.
    Hunter, Christine B.
    Jimenez-Shahed, Joohi
    Palao, Alicia
    Miyasaki, Janis M.
    Julie, S. O.
    Tetrud, James
    Reys, Liza
    Smith, Katharine
    Singer, Carlos
    Blenke, Anita
    Russell, David S.
    Cotto, Candace
    Friedman, Joseph H.
    Lannon, Margaret
    Zhang, Lin
    Drasby, Edward
    Kumar, Rajeev
    [J]. JAMA NEUROLOGY, 2014, 71 (05) : 543 - 552
  • [7] Beck AT Beck, 1987, INVENTORY DEPRESSION
  • [8] Use of antihypertensives and the risk of Parkinson disease
    Becker, Claudia
    Jick, Susan S.
    Meier, Christoph R.
    [J]. NEUROLOGY, 2008, 70 (16) : 1438 - 1444
  • [9] Differential contributions of cognitive and motor component processes to physical and instrumental activities of daily living in Parkinson's disease
    Cahn, DA
    Sullivan, EV
    Shear, PK
    Pfefferbaum, A
    Heit, G
    Silverberg, G
    [J]. ARCHIVES OF CLINICAL NEUROPSYCHOLOGY, 1998, 13 (07) : 575 - 583
  • [10] 'Rejuvenation' protects neurons in mouse models of Parkinson's disease
    Chan, C. Savio
    Guzman, Jaime N.
    Ilijic, Ema
    Mercer, Jeff N.
    Rick, Caroline
    Tkatch, Tatiana
    Meredith, Gloria E.
    Surmeier, D. James
    [J]. NATURE, 2007, 447 (7148) : 1081 - U5