PROJECT SUMMARY
Ischemic stroke affects 700,000 individuals annually in the U.S. and is the leading cause of long-term disability
in adults. Current acute stroke treatment paradigms (i.e., reperfusion therapies) are not widely applicable to
most patients due to a very narrow therapeutic window. New approaches that can be offered acutely to the
majority of ischemic stroke patients, and continued throughout the duration of post-stroke care, can limit stroke
severity, can complement or even enhance rehabilitation, and could transform ischemic stroke recovery. The
treatment of obstructive sleep apnea (OSA) among patients with acute ischemic stroke represents one such
novel therapeutic approach. The Recovery In Stroke Using PAP (RISE-UP) study is a randomized controlled
trial among 180 patients with acute ischemic stroke and moderate/severe OSA diagnosed by ambulatory
polysomnography comparing PAP treatment with usual care over 6 months. The randomization scheme will be
1:1:1 (n=60 acute intervention: n=60 subacute intervention: n=60 control/usual care). Acute intervention patients
will start PAP within 1-week post stroke symptom onset, and subacute patients will start PAP 1-month post
symptom onset. Both groups will continue PAP therapy through the duration of the study, reinforced with
technical assistance and behavioral support. All patients will receive a healthy lifestyle education intervention
focused on secondary stroke prevention. The primary outcome is functional stroke recovery at 6 months as
measured by the Modified Rankin Scale (mRS). Secondary outcomes measures include stroke severity
(NIHSS), the Berg Balance Scale, falls, actigraphic measures of motor activity, symptom measures of
sleepiness (ESS), vitality (SF-36), depression (PHQ-9), cognition (MoCA), and quality of life measures (SSQOL,
SAQLI). The Specific Aims: (1) Test whether a PAP treatment for OSA in ischemic stroke improves stroke
severity, post-stroke physical activity, post-stroke symptoms, and stroke functional recovery (primary outcome).
(2) Determine whether acute vs subacute initiation of PAP in ischemic stroke results in greater improvement in
post-stroke outcomes (stroke severity, physical activity, symptoms, stroke recovery). (3) Conduct qualitative, in
depth, interviews with 25-30 stroke patients, the family members, and acute care providers to elicit their
experience with PAP use, including factors that influence adherence. Exploratory Aim: Evaluate whether
polysomnographic measures have prognostic utility in understanding the variability in stroke recovery. This work
will be accomplished by an experienced multidisciplinary team of investigators (sleep medicine, nursing,
neurology, respiratory therapy, physiatry, and behavioral science) and will fulfill a critical step towards
developing new clinical practice pathways that involve treating OSA in ischemic stroke and developing more
personalized approaches for post-stroke care and PAP management.