Exercise and Cognitive Retraining to Improve Cognition in Heart Failure.

NCT02151266 | Completed Results DMC

• 2 other identifiers: IRB00060752P30NR014134
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive impairment (CI) is a prevalent problem in persons with HF heart failure (HF) and is associated with adverse clinical outcomes, higher mortality and poorer quality of life. Studies designed to attenuate or alleviate CI in persons with HF are limited, and evidenced based guidelines for screening and provision of care are practically nonexistent. Improvement in cognition has been reported following some therapies in HF and is thought to be the consequence of enhanced cerebral perfusion and oxygenation, suggesting that CI may be amenable to intervention in this population. Exercise is documented to increase cerebral perfusion and oxygenation by promoting neuroplasticity and neurogenesis, and, in turn, cognitive functioning. Brain derived neurotrophic factor (BDNF) is a key mechanism underlying the effect of exercise, but most studies of BDNF have not included individuals with CI or chronic illness populations, and its relationship to cognitive outcomes in HF is unknown. Cognitive retraining techniques, originally developed to treat traumatic brain injury, have also shown efficacy in broader neurologically-affected conditions and may provide added benefit to that of exercise. Animal studies suggest exercise and plasticity-based cognitive training could act synergistically through different neural mechanisms to have a more pronounced and positive impact on cognitive outcomes than either approach alone; but this has not been previously tested as an intervention to improve CI. The proposed feasibility study is designed to test the acceptability and limited efficacy of a combined exercise (Ex) and cognitive training (CT) program to improve CI in stable NYHA class II and III HF patients compared to either exercise alone or a no-intervention, attention-control group. Findings will be used to support the development of a future, large scale study to test the efficacy of this intervention to improve cognitive functioning, quality of life, and physiological markers of improved brain function in HF. In addition, we have an optional sub-study that participants may participate in order to further our understanding of biomarkers of inflammation and gen e expression before and after exercise.

Conditions

Heart Failure

Keywords

Heart failure; Exercise; Cognitive training

Outcome Measures

Primary Outcomes (5)

• Verbal Memory Score Change

  List Learning (0-40), List Recall (0-10), and List Recognition (0-20) sections from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) are used to assess Verbal memory.The range of scores for each section are in parentheses. Higher scores reflect better verbal memory. Scores are averaged for a total Verbal memory score, then converted to Z-score. Z-scores are used when neurocognitive test scores use different measurement scales, e.g., time to completion and number correct. This allows to report performance in a straightforward manner, with low and high scores reflecting poor and good performance consistently across different types of tests, and to provide interpretation of a person's performance in comparison to a group. For interpretive purposes, a z-score has a mean of 0 and a standard deviation of 1. This means that an individual who has a z-score of 1.5 is performing one and a half standard deviations above the group to which he/she is compared.

  Baseline, 3 months, 6 months

• Visual Memory Score Change

  Visual memory will be assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS figure recall requires the participant to remember a recent figure and redraw it from memory. The range of possible scores is 0-20. Scores are averaged, and then converted to z score. Z-scores are used when neurocognitive test scores use different measurement scales, e.g., time to completion and number correct. This allows to report performance in a straightforward manner, with low and high scores reflecting poor and good performance consistently across different types of tests, and to provide interpretation of a person's performance in comparison to a group. For interpretive purposes, a z-score has a mean of 0 and a standard deviation of 1. This means that an individual who has a z-score of 1.5 is performing one and a half standard deviations above the group to which he/she is compared.

  Baseline, 3 months, 6 months

• Change in Processing Speed/Attention Score

  RBANS coding (0-89) Color Trails 1 (timed test, 1-5 minutes) measures attention. The length of time to complete each part is recorded; lower raw scores reflect better processing speed and attention. Lower raw scores reflect better processing speed and attention. Scores are averaged for a total score, then converted to Z scores. Z-scores are used when neurocognitive test scores use different measurement scales, e.g., time to completion and number correct. This allows to report performance in a straightforward manner, with low and high scores reflecting poor and good performance consistently across different types of tests, and to provide interpretation of a person's performance in comparison to a group. For interpretive purposes, a z-score has a mean of 0 and a standard deviation of 1. This means that an individual who has a z-score of 1.5 is performing one and a half standard deviations above the group to which he/she is compared.

  Baseline, 3 months, 6 months

• Change in Working Memory Score

  Digit Span Forward (0-16), Digit Span Backwards (0-16), Digit Span Sequencing (0-16) and Letter Number Sequencing (0-48) sections from the Wechsler Adult Intelligence Scale - Fourth Edition are used to assess Working Memory. The range of possible scores for each section are in parentheses. The Digit Span subtest require the repetition of verbally presented series of numbers that increase in length; trials include the repeating of numbers in forward, backward, and numerical order. The Letter-Number sequencing test requires the repeating strings of letters and numbers in numerical and then in alphabetical order. Color Trails Test (CTT) Part 2, participants rapidly connect numbered circles in sequence while alternating between pink and yellow circles. Higher scores reflect better outcome. Scores reflect number correct and are averaged for total correct Working Memory score; are then converted to Z-score.

  Baseline, 3 months, 6 months

• Change in Reaction Time

  Scores are automatically calculated via the scoring software embedded within the CalCap and are standardized based on age and education level norms. Normative data are stratified by both age (20-34, 35-44, 45+) and education (\< 16 years, 16 years, \> 16 years). Lower scores reflect slower reaction time and higher scores reflect faster reaction time. Scores are automatically converted to age/education based standard scores and are reported as a T-score. T-scores (as Z-scores) are used when neurocognitive test scores use different measurement scales, e.g., time to completion and number correct. This allows to report performance in a straightforward manner, with low and high scores reflecting poor and good performance consistently across different types of tests, and to provide interpretation of a person's performance in comparison to a group.

  Baseline, 3 months, 6 months

Secondary Outcomes (1)

• Functional Capacity

  Baseline, 3 months, 6 months

Other Outcomes (1)

• Peak V02

  Baseline and 3 months

Study Arms (3)

Exercise and Cognitive retraining

EXPERIMENTAL

Aerobic exercise; Computerized cognitive retraining program; Heart failure education; Home visits; telephone follow-up.

Behavioral: Exercise and Cognitive retraining

Exercise only

EXPERIMENTAL

Each participant will be provided with an individualized target heart rate (THR)zone based on treadmill results. Under the supervision of a research nurse, participants will begin the walking sessions at 60% of THR and increase to 70% by week 5. Participants will walk a minimum of 5 times per week for a duration of 30 minutes.

Behavioral: Exercise Only

Stretching and Flexibility

SHAM COMPARATOR

Stretching and flexibility movements; heart failure education; home visits; telephone follow-up.

Behavioral: Stretching and Flexibility

Interventions

Exercise and Cognitive retraining BEHAVIORAL

Walking 5 times per week at moderate intensity; cognitive retraining one-hour 2 times per week.

Also known as: Aerobic exercise; walking and computerized cognitive retraining program

Exercise and Cognitive retraining

Exercise Only BEHAVIORAL

Exercise only

Stretching and Flexibility BEHAVIORAL

Stretching and Flexibility

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men and women between the ages of 40 and 75; English speaking; live independently within a 60 mile radius of Atlanta; meet education corrected cut-offs on the MMSE indicating cognitive impairment (score of 20 for 8-9 yrs of schooling; 22 for 10-12 yrs of schooling; 23 for \>12 yrs) have a computer with internet connection; documented medical diagnosis of NYHA class II or III systolic. Left ventricular ejection fraction (LVEF) ≥ 10% that is documented within the last year by echocardiogram, cardiac catheterization ventriculography or radionuclide ventriculography; Receiving medication therapy for HF according to American College of Cardiology (ACC) American Heart recommendation guidelines for at least 8 weeks prior to study enrollment.

You may not qualify if:

• NYHA class I or IV; change in HF therapy within 8 weeks; worsening HF symptoms within last 5 days; unstable angina; renal insufficiency (serum creatinine \> 3.o mg/dL); fixed rate pacemaker; uncontrolled hypertension; not involved in any structured exercise program or exercising 3 or more times per week for a minimum of 30 minutes and; not hospitalized within the last 30-days; not diagnosed with any neurological disorder that may interfere with cognitive function; Beck Depression Inventory II (BDI-II) score greater than 25; any disorder interfering with exercise participation.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Nursing Research (NINR): collaborator

Study Sites (1)

Emory University Heart Failure Clinics

Atlanta, Georgia, 30322, United States

Location

Related Publications (2)

• Gary RA, Paul S, Corwin E, Butts B, Miller AH, Hepburn K, Waldrop D. Exercise and Cognitive Training Intervention Improves Self-Care, Quality of Life and Functional Capacity in Persons With Heart Failure. J Appl Gerontol. 2022 Feb;41(2):486-495. doi: 10.1177/0733464820964338. Epub 2020 Oct 13.

  PMID: 33047625 DERIVED

• Gary RA, Paul S, Corwin E, Butts B, Miller AH, Hepburn K, Williams B, Waldrop-Valverde D. Exercise and Cognitive Training as a Strategy to Improve Neurocognitive Outcomes in Heart Failure: A Pilot Study. Am J Geriatr Psychiatry. 2019 Aug;27(8):809-819. doi: 10.1016/j.jagp.2019.01.211. Epub 2019 Feb 1.

  PMID: 30910420 DERIVED

MeSH Terms

Conditions

Heart Failure; Motor Activity

Interventions

Exercise; Walking; Pliability

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Locomotion; Mechanical Phenomena; Physical Phenomena

Results Point of Contact

• Title: Dr. Gary
• Organization: Emory University

ragary@emory.edu

404-727-8360

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: May 30, 2014
• Study Start: July 1, 2013
• Primary Completion: December 30, 2017
• Study Completion: December 30, 2017
• Last Updated: January 25, 2021
• Results First Posted: August 14, 2019

Record last verified: 2019-07

Locations

US (1)