Improving Recovery and Outcomes Every Day after the ICU (IMPROVE): study protocol for a randomized controlled trial

Sophia Wang, Jessica Hammes, Sikandar Khan, Sujuan Gao, Amanda Harrawood, Stephanie Martinez, Lyndsi Moser, Anthony Perkins, Frederick W Unverzagt, Daniel O Clark, Malaz Boustani, Babar Khan, Sophia Wang, Jessica Hammes, Sikandar Khan, Sujuan Gao, Amanda Harrawood, Stephanie Martinez, Lyndsi Moser, Anthony Perkins, Frederick W Unverzagt, Daniel O Clark, Malaz Boustani, Babar Khan

Abstract

Background: Delirium affects nearly 70% of older adults hospitalized in the intensive care unit (ICU), and many of those will be left with persistent cognitive impairment or dementia. There are no effective and scalable recovery models to remediate ICU-acquired cognitive impairment and its attendant elevated risk for dementia or Alzheimer disease (AD). The Improving Recovery and Outcomes Every Day after the ICU (IMPROVE) trial is an ongoing clinical trial which evaluates the efficacy of a combined physical exercise and cognitive training on cognitive function among ICU survivors 50 years and older who experienced delirium during an ICU stay. This article describes the study protocol for IMPROVE.

Methods: IMPROVE is a four-arm, randomized controlled trial. Subjects will be randomized to one of four arms: cognitive training and physical exercise; cognitive control and physical exercise; cognitive training and physical exercise control; and cognitive control and physical exercise control. Facilitators administer the physical exercise and exercise control interventions in individual and small group formats by using Internet-enabled videoconference. Cognitive training and control interventions are also facilitator led using Posit Science, Inc. online modules delivered in individual and small group format directly into the participants' homes. Subjects complete cognitive assessment, mood questionnaires, physical performance batteries, and quality of life scales at baseline, 3, and 6 months. Blood samples will also be taken at baseline and 3 months to measure pro-inflammatory cytokines and acute-phase reactants; neurotrophic factors; and markers of glial dysfunction and astrocyte activation.

Discussion: This study is the first clinical trial to examine the efficacy of combined physical and cognitive exercise on cognitive function in older ICU survivors with delirium. The results will provide information about potential synergistic effects of a combined intervention on a range of outcomes and mechanisms of action.

Trial registration: ClinicalTrials.gov, NCT03095417 . Registered on 23 March 2017. Last updated on 15 May 2017.

Keywords: Aging; Alzheimer disease; Biomarkers; Cognitive impairment; Cognitive training; Critical care; Delirium; Dementia; Internet delivery; Physical activity; Physical exercise; Post-intensive care syndrome.

Conflict of interest statement

Ethics approval and consent to participate

The protocol was approved by the Institutional Review Board at the Indiana University School of Medicine, #1608126693. The principal investigator and the research staff are responsible for conducting the informed consent process with all the study participants. Informed consent will be obtained from the subject or their legally authorized representative as appropriate. Changes to the study protocol and/or the informed consent will be sent to the Institutional Review Board as protocol amendments. All data will be de-identified prior to analysis; only the principal investigator and project manager will be able to access the code to identify the individual. The protocol was registered in ClinicalTrials.gov NCT03095417 on March 23, 2017 (https://ichgcp.net/clinical-trials-registry/NCT03095417?term=NCT03095417&recrs=ab&rank=1) before starting the trial, and trial status will be updated accordingly.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests. The funding agency had no role in the development of the study design, collection, analysis, interpretation of data, manuscript development, or the decision to submit the manuscript for publication.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Proposed pathophysiologic model linking delirium and dementia (number of arrows depicting magnitude)
Fig. 2
Fig. 2
Conceptual model of the IMPROVE study
Fig. 3
Fig. 3
Eligibility, randomization, allocation, and follow-up outcomes
Fig. 4
Fig. 4
Schedule of enrollment, interventions, and assessments. GAD-7 Generalized Anxiety Disorder-7; PHQ-9 Patient Health Questionnaire-9; RBANS Repeatable Assessment of Neuropsychological Status; SF-36 36-Item Short Form Health Survey; SPPB Short Physical Performance Battery

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