Improving the Recovery and Outcome Every Day After the ICU

NCT03095417 | Completed Results DMC

• 2 other identifiers: 1608126693R01AG055391
• Study Type: interventional
• Target: 249
• Locations: 1 country
• Sites: 6

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. Exploratory 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.

Conditions

Delirium; Alzheimer Disease

Keywords

Delirium; Alzheimer's Disease; Aging; Exercise Therapy; Cognitive Training

Outcome Measures

Primary Outcomes (2)

• Cognitive Status Outcome at 6 Months

  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will measure cognitive status. The z-scores for the subscales have a mean of 0 and standard deviation of 1. The overall z-score is the mean of the 7-item z-scores. Z-scores above the standard deviation represent better cognitive outcomes.

  6 months post study randomization

• Cognitive Status Outcome at 3 Months

  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will measure cognitive status. The z-scores for the subscales have a mean of 0 and standard deviation of 1. The overall z-score is the mean of the 7-item z-scores. Z-scores above the standard deviation represent better cognitive outcomes.

  3 months post study randomization

Secondary Outcomes (10)

• Physical Performance Scores at 3 Months

  3 month post study randomization

• Physical Performance Scores at 6 Months

  6 month post study randomization

• Cardiovascular Fitness Scores at 3 Months

  3 month post study randomization

• Cardiovascular Fitness Scores at 6 Months

  6 month post study randomization

• Depression Scores at 3 Months

  3 month post study randomization

Study Arms (4)

Physical Exercise and Cognitive Training

EXPERIMENTAL

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; Behavioral: Cognitive Training Intervention

Physical Exercise and Cognitive Control

ACTIVE COMPARATOR

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; Behavioral: Cognitive Control

Cognitive Training and Stretching Control

ACTIVE COMPARATOR

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; Behavioral: Stretching Control

Cognitive Control and Stretching Control

SHAM COMPARATOR

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; Behavioral: Cognitive Control

Interventions

Physical Exercise Intervention BEHAVIORAL

In home exercise intervention.

Physical Exercise and Cognitive Control; Physical Exercise and Cognitive Training

Cognitive Training Intervention BEHAVIORAL

Online cognitive training modules.

Also known as: Brain HQ

Cognitive Training and Stretching Control; Physical Exercise and Cognitive Training

Stretching Control BEHAVIORAL

In home stretching.

Cognitive Control and Stretching Control; Cognitive Training and Stretching Control

Cognitive Control BEHAVIORAL

Online control puzzles and games.

Also known as: Brain HQ

Cognitive Control and Stretching Control; Physical Exercise and Cognitive Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (6)

Indiana University Health West Hospital

Avon, Indiana, 46123, United States

Location

Indiana University Health North Hospital

Carmel, Indiana, 46032, United States

Location

Indiana University Health Saxony Hospital

Fishers, Indiana, 46037, United States

Location

Eskenazi Health

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Related Publications (2)

• Khan SH, Perkins AJ, Unverzagt FW, Wang S, Moser LR, Moiz S, Jawaid S, Corlett D, Clark DO, Boustani MA, Gao S, Khan BA. Improving Recovery and Outcomes Every Day After the ICU (IMPROVE): A Randomized Controlled Trial. Crit Care Med. 2025 Aug 1;53(8):e1542-e1553. doi: 10.1097/CCM.0000000000006698. Epub 2025 May 22.

  PMID: 40402024 DERIVED

• Wang S, Hammes J, Khan S, Gao S, Harrawood A, Martinez S, Moser L, Perkins A, Unverzagt FW, Clark DO, Boustani M, Khan B. Improving Recovery and Outcomes Every Day after the ICU (IMPROVE): study protocol for a randomized controlled trial. Trials. 2018 Mar 27;19(1):196. doi: 10.1186/s13063-018-2569-8.

  PMID: 29580264 DERIVED

MeSH Terms

Conditions

Delirium; Alzheimer Disease

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Babar Khan, MD, MS
• Organization: Indiana University

bakhan@iu.edu

(317) 274-9132

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: March 29, 2017
• Study Start: September 25, 2017
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: March 27, 2024
• Results First Posted: March 27, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)