title: Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial.
abstract: BACKGROUND
  Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach.
  
  
  METHODS
  In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2-3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies.
  
  
  CONCLUSIONS
  CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial.
authors.affiliation: Department of Rehabilitation Medicine, Center for Brain Plasticity and Recovery, Georgetown University and MedStar National Rehabilitation Hospital Washington, DC, USA ; Department of Neurology, Georgetown University Washington, DC, USA.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Dromerick
authors.affiliation: Department of Rehabilitation Medicine, Center for Brain Plasticity and Recovery, Georgetown University and MedStar National Rehabilitation Hospital Washington, DC, USA ; Department of Neurology, Georgetown University Washington, DC, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Edwardson
authors.affiliation: Department of Kinesiology and Occupational Therapy, University of Wisconsin Madison, WI, USA.
authors.forename: Dorothy F
authors.initials: DF
authors.lastname: Edwards
authors.affiliation: Department of Rehabilitation Medicine, Center for Brain Plasticity and Recovery, Georgetown University and MedStar National Rehabilitation Hospital Washington, DC, USA.
authors.forename: Margot L
authors.initials: ML
authors.lastname: Giannetti
authors.affiliation: Department of Rehabilitation Medicine, Center for Brain Plasticity and Recovery, Georgetown University and MedStar National Rehabilitation Hospital Washington, DC, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Barth
authors.affiliation: Department of Rehabilitation Medicine, Center for Brain Plasticity and Recovery, Georgetown University and MedStar National Rehabilitation Hospital Washington, DC, USA.
authors.forename: Kathaleen P
authors.initials: KP
authors.lastname: Brady
authors.affiliation: Department of Rehabilitation Medicine, Center for Brain Plasticity and Recovery, Georgetown University and MedStar National Rehabilitation Hospital Washington, DC, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Chan
authors.affiliation: Department of Biostatistics, Georgetown University Washington, DC, USA.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tan
authors.affiliation: Department of Neuroscience, Georgetown University Washington, DC, USA.
authors.forename: Irfan
authors.initials: I
authors.lastname: Tamboli
authors.affiliation: Department of Neuroscience, Georgetown University Washington, DC, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Chia
authors.affiliation: Department of Neuroscience, Georgetown University Washington, DC, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Orquiza
authors.affiliation: Department of Neuroscience, Georgetown University Washington, DC, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Padilla
authors.affiliation: Departments of Oncology and Biochemistry, Georgetown University Washington, DC, USA.
authors.forename: Amrita K
authors.initials: AK
authors.lastname: Cheema
authors.affiliation: Department of Neurology, University of Rochester Rochester, NY, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Mapstone
authors.affiliation: Department of Neurology, Georgetown University Washington, DC, USA ; Department of Neuroscience, Georgetown University Washington, DC, USA.
authors.forename: Massimo S
authors.initials: MS
authors.lastname: Fiandaca
authors.affiliation: Department of Neurology, Georgetown University Washington, DC, USA ; Department of Neuroscience, Georgetown University Washington, DC, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
authors.affiliation: Department of Rehabilitation Medicine, Center for Brain Plasticity and Recovery, Georgetown University and MedStar National Rehabilitation Hospital Washington, DC, USA ; Department of Neurology, Georgetown University Washington, DC, USA.
authors.forename: Elissa L
authors.initials: EL
authors.lastname: Newport
keywords: adaptive randomization; cerebrovascular disorders; critical period; motor recovery; multi-omics; stroke rehabilitation