External Counterpulsation for MCI/ AD: Study Design
Pivotal Trial Design
Treatment of Mild Cognitive Impairment due to Alzheimer's Disease or Mild Dementia of the Alzheimer's Type: Design and Rationale of the Randomized Pivotal Study of Renew NCP-5
Alzheimer's association international conference: abstract 2019
Patrick M Moriarty, Lauryn K Gorby, Eric Ecklund-Johnson, William Brooks, Rebecca Lepping, David H Salat, Jonathan Helfgott, and Jeffrey M Burns
Background: Vascular dementia and Alzheimer’s disease (AD) share an association with hemodynamic risk factors. Exercise can improve cerebral blood flow (CBF), which is associated with a decrease in cognitive decline. However, patients with AD or mild cognitive impairment (MCI) may have limited exercise capacity due to age-related physical restrictions. RenewTM NCP-5 is an FDA-cleared, external counterpulsation (ECP) device, which consistently improves coronary and peripheral vascular hemodynamics by sequential compression and decompression of vascular beds in synchrony with the cardiac cycle (Figure 1), and is currently used to treat patients with chronic angina and congestive heart failure. ECP may provide the same hemodynamic benefit for cerebral perfusion and cognitive function.
Methods: This randomized, Phase 3, pivotal, single-blind, parallel design, multi-center study (NCT03721705) will assess the efficacy of RenewTM NCP-5 in patients with MCI due to AD or mild dementia (MD) of Alzheimer’s type at 16 sites in the USA, Europe, and Asia. Study participants (see Table 1 for key entry criteria) will be randomized 1:1 to receive a bolus of 35 60-minute RenewTM NCP-5 treatment sessions or sham therapy with 3–5 sessions per week. Following the initial 35 treatments, a maintenance period will begin with two treatment sessions per week for up to 24 weeks total. (Figure 2). The primary efficacy endpoint is the average of the change from baseline in Vascular Dementia Assessment Scale cognitive subscale (vADAS-Cog) at Weeks 12, 18, and 24. Safety is assessed throughout the study; other key assessments, including the measurement of CBF as a potential mechanistic index of therapeutic engagement through arterial spin labelling perfusion MRI, are presented in Figure 2. At month 12, all subjects will undergo a full assessment, and the sham group will have the option to enter an open-label extension.
Results: We hypothesise that RenewTM NCP-5 therapy will lead to effective treatment or delay of cognitive impairment in study participants.
Conclusion: This pivotal study aims to evaluate the efficacy and safety of RenewTM NCP-5 as a therapeutic option for patients with MCI due to AD or MD of Alzheimer’s type.