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Improving the Recovery and Outcome Every Day After the ICU (IMPROVE)

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ClinicalTrials.gov Identifier: NCT03095417
Recruitment Status : Recruiting
First Posted : March 29, 2017
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
Babar Khan, MD, MS, Indiana University

Brief Summary:

Primary Specific Aim: Determine the effect of the combined physical exercise and cognitive training on the cognitive function of ICU survivors aged 50 and older. Hypothesis: In comparison to older ICU survivors randomized to attention control or either intervention alone, those randomized to 12 weeks of combined physical exercise and cognitive training will have higher total index cognitive scores as assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at 3 and 6 months post randomization.

Secondary Specific Aim 1: Determine the effect of the combined physical exercise and cognitive training on physical performance, anxiety and depressive symptoms, and quality of life of ICU survivors aged 50 and older. Hypotheses: In comparison to older ICU survivors randomized to attention control or either intervention alone, those randomized to 12 weeks of combined physical exercise and cognitive training will have higher physical performance as measured by short physical performance battery (SPPB) and two-minute step test, lower mood and anxiety symptoms as measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale, and higher quality of life as measured by the Medical Outcomes Study 36-item short form (SF-36) at 3 and 6-months post randomization.

Secondary Specific Aim 2: To examine the mechanisms of action of combined training. Hypothesis: At the completion of treatment, the combined intervention group will show reduced serum levels of CRP, IL-1, IL-6, IL-8, TNF-α, S-100β, and GFAP and increased levels of BDNF, VEGF, and IGF-1 compared to the attention control, or either intervention alone groups.


Condition or disease Intervention/treatment Phase
Delirium Alzheimer Disease Behavioral: Physical Exercise Intervention Behavioral: Cognitive Training Intervention Behavioral: Stretching Control Behavioral: Cognitive Control Not Applicable

Detailed Description:

Critical illness has deleterious consequences on both acute and chronic cognitive functions. Acute cognitive dysfunction manifests itself as delirium in the critically ill especially the elderly. Delirium is a complex neuropsychiatric syndrome characterized by acute and fluctuating changes in cognition and consciousness. 60% to 80% of critically ill ventilated older patients and 30% to 50% of those with less illness severity have delirium for at least one day of their ICU or hospital stay. Chronic cognitive dysfunction manifests as ICU acquired cognitive impairment and dementia after critical illness, affects multiple cognitive domains and persists years after hospital discharge. Up to 71% of critical illness survivors have cognitive impairment at one year after hospital discharge and close to 18% are diagnosed with new dementia including Alzheimer's disease within three years post ICU hospitalization.

Two million older Americans suffer from an episode of delirium during their intensive care unit (ICU) stay. Presence of delirium predisposes the elderly to immediate in-hospital complications including a longer length of ICU and hospital stay, increased risk of in-patient mortality and elevated costs of care. In addition, ICU delirium is associated with long-term post-discharge complications such as development of cognitive impairment and dementia. Current advances in the management of critical illness have notably improved the survival rates among this vulnerable segment of older adults. However, increased survival comes at a cost with as many as 70% of older ICU survivors who had an episode of delirium suffering from subsequent cognitive impairment and dementia. At present, there are no effective and scalable recovery models to remediate ICU acquired cognitive impairment and its attendant elevated dementia or Alzheimer's disease risk.

The inability to develop efficacious interventions to reduce ICU acquired cognitive impairment may stem from a limited understanding of the link between acute brain dysfunction (delirium) and chronic brain dysfunction (ICU acquired cognitive impairment, dementia or Alzheimer's disease). The investigators propose a recovery intervention guided by the pathophysiologic mechanisms implicated in producing critical illness delirium and elevated risk of cognitive impairment. The intervention targets inflammation, glial dysfunction and astrocyte activation along with restoration of neurotrophic factors while training function directly across multiple cognitive domains to reduce the burden of cognitive impairment among ICU survivors of delirium.

Over the past five years, Indiana University Center for Aging Research has developed a research infrastructure focused on delirium and delirium associated cognitive impairment, encompassing the ICU and post-ICU periods. This includes developing a bio-repository of serum delirium biomarkers, ICU based delirium trials, and post-ICU exercise and cognitive therapy recovery models. Building upon prior work and based on the pathophysiologic mechanisms mentioned above, the investigators now propose a novel home-based combined physical exercise and cognitive training program for older ICU survivors to improve cognitive impairment.

The study team is proposing a 2x2 factorial design randomized controlled trial (RCT) called "Decreasing Alzheimer's Disease and Related Dementias after Delirium-Exercise and Cognitive Training (DDD-ECT)" to evaluate the efficacy of 12 weeks of combined physical exercise and cognitive training on the primary outcome of cognitive function among older ICU survivors who experienced delirium or subsyndromal delirium during their ICU stay. The investigators propose to deliver these interventions via a facilitator-led, small group format using internet-enabled, multiparty-videoconference delivered directly into the participants' homes to achieve the study aims listed in the summary.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 344 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Decreasing Alzheimer's Disease and Related Dementias After Delirium- Exercise and Cognitive Training
Actual Study Start Date : September 25, 2017
Estimated Primary Completion Date : June 1, 2022
Estimated Study Completion Date : June 1, 2023


Arm Intervention/treatment
Experimental: Physical Exercise and Cognitive Training

Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months.

Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory.

Behavioral: Physical Exercise Intervention
In home exercise intervention.

Behavioral: Cognitive Training Intervention
Online cognitive training modules.
Other Name: Brain HQ

Active Comparator: Physical Exercise and Cognitive Control

Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months.

Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control.

Behavioral: Physical Exercise Intervention
In home exercise intervention.

Behavioral: Cognitive Control
Online control puzzles and games.
Other Name: Brain HQ

Active Comparator: Cognitive Training and Stretching Control

Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months.

Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions.

Behavioral: Cognitive Training Intervention
Online cognitive training modules.
Other Name: Brain HQ

Behavioral: Stretching Control
In home stretching.

Sham Comparator: Cognitive Control and Stretching Control

Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months.

Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control.

Behavioral: Stretching Control
In home stretching.

Behavioral: Cognitive Control
Online control puzzles and games.
Other Name: Brain HQ




Primary Outcome Measures :
  1. Cognitive Status Outcome at 6 months [ Time Frame: 6 months post study randomization ]
    The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will be used to measure cognitive status.

  2. Cognitive Status Outcome at 3 months [ Time Frame: 3 months post study randomization ]
    The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will be used to measure cognitive status.


Secondary Outcome Measures :
  1. Quality of Life Scores at 3 months [ Time Frame: 3 month post study randomization ]
    The Medical Outcomes Study 36 item short form (SF-36) will measure participant quality of life scores.

  2. Quality of Life Scores at 6 months [ Time Frame: 6 month post study randomization ]
    The Medical Outcomes Study 36 item short form (SF-36) will measure participant quality of life scores.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged ≥ 50 years
  • Admitted to medical and/or surgical ICUs at Methodist, University, or Eskenazi hospitals
  • Discharged home or to sub-acute rehabilitation, long-term acute care, or skilled nursing facility
  • Able to provide consent or has a legally authorized representative to provide consent
  • Access to a telephone (study provides computer and broadband)
  • Have at least one episode of subsyndromal delirium or delirium as determined by the Confusion Assessment Method for the ICU-7 (CAM-ICU).

Exclusion Criteria:

  • Diagnosis of cancer with short life expectancy
  • Current chemotherapy or radiation therapy (confirmed by electronic medical record)
  • History of dementing illnesses and other neurodegenerative disease such as Alzheimer's disease, Parkinson disease, or vascular dementia (confirmed by EMR), or current prescription of anti-dementia medication, or ruled out by Functional Activities Questionnaire (FAQ) score defining dementia
  • History of bipolar disorder or schizophrenia (confirmed by EMR)
  • Current alcohol consumption > 5 drinks per day (self reported and/or confirmed by EMR)
  • Vision < 20/80 via Snellen card or confirmed by EMR
  • Low hearing or communicative ability (examiner rated) that would interfere with interventions and outcome assessments
  • Have any active and untreated American College of Sports Medicine absolute contraindications to exercise (confirmed by EMR) including: acute myocardial infarctions within the past 2 days, ongoing unstable angina, uncontrolled cardiac arrhythmia with hemodynamic compromise, active endocarditis, symptomatic severe aortic stenosis, decompensated heart failure, acute pulmonary embolism, pulmonary infarction, or deep venous thrombosis, acute myocarditis or pericarditis, acute aortic dissection, physical disability that precludes safe and adequate testing, or are unable to obtain provider clearance for physical exercise for any contraindication where medical management is unclear
  • Have any active and untreated American College of Sports Medicine relative contraindications to exercise (confirmed by EMR) including: known obstructive left main coronary stenosis, moderate to severe aortic stenosis with uncertain relationship to symptoms, tachydysrhythmias with uncontrolled ventricular rates, acquired advanced or complete heart block, recent stroke or transient ischemia attack, mental impairment with limited ability to cooperate, resting hypertension with systolic >200 mm Hg or diastolic >100 mm Hg, uncorrected medical conditions, such as significant anemia, important electrolyte imbalance, and hyperthyroidism, or are unable to obtain provider clearance for physical exercise for any contraindication where medical management is unclear
  • Recovering from a skeletal fracture (confirmed by EMR), unless cleared by their physician of record to safely participate in exercise
  • Acquired neurologic injury (stroke, traumatic brain injury, cerebral edema/swelling, anoxic brain injury, or any other acute/subacute severe neurologic deficit) as the admitting diagnosis or a new event during the course of hospitalization (confirmed by EMR)
  • History of drug abuse within the last 3 months confirmed by EMR or self-report with Drug Abuse and Screening Test (DAST-10) score ≥ 3
  • Have any spinal cord injury with persistent neurologic deficit at the time of study enrollment
  • Status post tracheostomy and not eligible for a speaking valve
  • Pregnant or nursing
  • Incarcerated or homeless at time of study
  • Lives outside the greater Indianapolis area

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03095417


Contacts
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Contact: Lyndsi R Moser, BA 317-963-7301 lrhabegg@iupui.edu
Contact: Lori Rawlings, BSN, RN 317-274-9052 rawlingl@regenstrief.org

Locations
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United States, Indiana
Indiana University Health West Hospital Not yet recruiting
Avon, Indiana, United States, 46123
Contact: Babar Khan, MD         
Indiana University Health North Hospital Not yet recruiting
Carmel, Indiana, United States, 46032
Contact: Babar Khan, MD         
Indiana University Health Saxony Hospital Not yet recruiting
Fishers, Indiana, United States, 46037
Contact: Babar Khan, MD         
Eskenazi Health Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Babar Khan, MD         
Indiana University Health Methodist Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Babar Khan, MD         
Indiana University Health University Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Babar Khan, MD         
Sponsors and Collaborators
Indiana University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Babar Khan, MD, MS, Assistant Professor of Medicine, Indiana University
ClinicalTrials.gov Identifier: NCT03095417     History of Changes
Other Study ID Numbers: 1608126693
First Posted: March 29, 2017    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Babar Khan, MD, MS, Indiana University:
Delirium
Alzheimer's Disease
Aging
Exercise Therapy
Cognitive Training
Additional relevant MeSH terms:
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Alzheimer Disease
Delirium
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms