Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02875301
Recruitment Status : Recruiting
First Posted : August 23, 2016
Last Update Posted : May 11, 2020
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Kirk Erickson, PhD, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE August 12, 2016
First Posted Date  ICMJE August 23, 2016
Last Update Posted Date May 11, 2020
Actual Study Start Date  ICMJE September 6, 2017
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2016)
Change in Cognitive Function [ Time Frame: Baseline, 6 months, and 12 months ]
Investigators are assessing change in cognitive function from baseline to 12 months. The 6 month measure is being used to assess the trajectory of the change. A comprehensive neuropsychological battery will be used that assesses 8 domains of cognitive function (Executive Function, Working Memory, Processing Speed, Episodic Memory, Reasoning, Spatial Processing, Vocabulary / Language, and Experience Based Learning).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2020)
  • Change in brain morphology [ Time Frame: Baseline and 12 months ]
    MRI will be used to measure brain morphology including volume, cortical thickness, hippocampal subfields, and white matter structure and lesions.
  • Change in brain activity [ Time Frame: Baseline and 12 months ]
    MRI will be used to measure changes in brain activity including both resting state and task-evoked patterns.
  • Change in cerebral blood flow [ Time Frame: Baseline and 12 months ]
    MRI will be used to measure changes in cerebral blood flow.
  • Change in Body Composition [ Time Frame: Baseline and 12 Months ]
    This will be assessed using a dual-energy x-ray absorptiometer (DXA). The DXA will provide a measure of lean mass, fat mass, and bone content and density from a total body scan and will be used to estimate abdominal adiposity.
  • Change in Arterial Stiffness [ Time Frame: Baseline and 12 months ]
    This is measured by Carotid-Femoral Pulse Wave Velocity. This outcome is measured by capturing pulse pressure waveforms from the right carotid and femoral arteries using tonometry after 10 minutes of supine rest.
  • Change in Cardiorespiratory Fitness [ Time Frame: Baseline and 12 Months ]
    Fitness is assessed by maximal graded exercise testing. Oxygen uptake (VO2) will be measured from expired air samples taken at 15 second intervals until a peak VO2, the highest VO2, is attained at the point of test termination due to symptom limitation and/or volitional exhaustion.
  • Change in Blood Biomarkers [ Time Frame: Baseline, 6 Months, and 12 Months ]
    Brain Derived Neurotrophic factor (BDNF), Insulin Growth Factor-1 (IGF-1), glucose and insulin levels, inflammatory cytokines.
  • Beta Amyloid [ Time Frame: Baseline and 12 Months ]
    Florbetapir F 18 or Amyvid PET scans will be obtained at baseline and qualitatively read and quantitatively assessed (according to ADNI guidelines) to establish the presence or absence of cerebral amyloidosis.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2016)
  • Change in brain morphology [ Time Frame: Baseline and 12 months ]
    MRI will be used to measure brain morphology including volume, cortical thickness, hippocampal subfields, and white matter structure and lesions.
  • Change in brain activity [ Time Frame: Baseline and 12 months ]
    MRI will be used to measure changes in brain activity including both resting state and task-evoked patterns.
  • Change in cerebral blood flow [ Time Frame: Baseline and 12 months ]
    MRI will be used to measure changes in cerebral blood flow.
  • Change in Body Composition [ Time Frame: Baseline and 12 Months ]
    This will be assessed using a dual-energy x-ray absorptiometer (DXA). The DXA will provide a measure of lean mass, fat mass, and bone content and density from a total body scan and will be used to estimate abdominal adiposity.
  • Change in Arterial Stiffness [ Time Frame: Baseline and 12 months ]
    This is measured by Carotid-Femoral Pulse Wave Velocity. This outcome is measured by capturing pulse pressure waveforms from the right carotid and femoral arteries using tonometry after 10 minutes of supine rest.
  • Change in Cardiorespiratory Fitness [ Time Frame: Baseline and 12 Months ]
    Fitness is assessed by maximal graded exercise testing. Oxygen uptake (VO2) will be measured from expired air samples taken at 30 second intervals until a peak VO2, the highest VO2, is attained at the point of test termination due to symptom limitation and/or volitional exhaustion.
  • Change in Blood Biomarkers [ Time Frame: Baseline, 6 Months, and 12 Months ]
    Brain Derived Neurotrophic factor (BDNF), Insulin Growth Factor-1 (IGF-1), glucose and insulin levels, inflammatory cytokines.
  • Beta Amyloid [ Time Frame: Baseline ]
    Florbetapir F 18 or Amyvid PET scans will be obtained at baseline and qualitatively read and quantitatively assessed (according to ADNI guidelines) to establish the presence or absence of cerebral amyloidosis.
Current Other Pre-specified Outcome Measures
 (submitted: April 11, 2019)
  • Change in Exercise Frequency [ Time Frame: Every 2 months starting at baseline until follow-up at 12 months ]
    Exercise frequency will be measured using Actigraph Link physical activity monitoring device. This device is small and lightweight. It is worn around the non-dominant wrist(touching the skin) for approximately 7 days during all waking and sleeping hours.
  • Change in Exercise Duration [ Time Frame: Every 2 months starting at baseline until follow-up at 12 months ]
    Exercise duration will be measured using Actigraph Link physical activity monitoring device. This device is small and lightweight. It is worn around the non-dominant wrist (touching the skin) for approximately 7 days during all waking and sleeping hours.. The duration is measured in minutes.
  • Change in Exercise Intensity [ Time Frame: Every 2 months starting at baseline until follow-up at 12 months ]
    Exercise duration will be measured using Actigraph Link physical activity monitoring device. This device is small and lightweight. It is worn around the non-dominant wrist (touching the skin) for approximately 7 days during all waking and sleeping hours.. The duration is measured in minutes.
  • Change in lower extremity performance [ Time Frame: Baseline and 12 months ]
    Short Physical Performance Battery (SPPB)
  • Change in functional fitness of basic activities of daily living [ Time Frame: Baseline and 12 months ]
    Senior Fitness Test
  • Change in health related quality of life [ Time Frame: Baseline and 12 months ]
    The 12-Item Short Form Survey (SF-12) is a practical, reliable, and valid measure of mental health and physical function.
  • Change in perceived stress [ Time Frame: Baseline and 12 months ]
    The Perceived Stress Scale (PSS) is one of the most widely used psychological instruments for measuring the perception of stress. It measures the degree to which situations in the participants life are gauged as stressful.
  • Change in quality of life [ Time Frame: Baseline and 12 months ]
    Investigators will use Satisfaction with Life Scale (SWLS) as global cognitive judgement of study participants Life Satisfaction which is one factor in the overall subjective well being.
  • Change in exercise self-efficacy [ Time Frame: Baseline and 12 months ]
    The investigators will use the Exercise Self-Efficacy Scale (EXSE) to assess the study participants belief in their ability to continue exercising three times a week at moderate intensity for 40 plus minutes a session in the future.
  • Change in mood [ Time Frame: Baseline and 12 months ]
    The Geriatric Depression Scale (GDS) will be used. It is an instrument used exclusively with older populations. The scale uses yes and no questions to gauge level of depression in the elderly.
  • Change in anxiety symptoms [ Time Frame: Baseline and 12 months ]
    Positive and Negative Affect Schedule (PANAS)
  • Change in Cortisol Levels [ Time Frame: Baseline and 12 months ]
    Hair Sample
  • Calculate the Incremental Cost Effectiveness Ratio (ICER) gained of the INTERVENTION [ Time Frame: Baseline, 6 months, and 12 months ]
    Health Resource Utilization
  • Gait Analysis [ Time Frame: Baseline and 12 Months ]
    Normal walking trials versus dual task walking trials (45 seconds each trial)
  • Incremental cost per quality adjusted life year (QALY) gained from the intervention [ Time Frame: Baseline, 6 months, and 12 months ]
    The 5 level Euro. Quality of Life 5D (EQ-5D-5L) Questionnaire The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions are then combined into a 5-digit number that describes the patient's health state. Example, no problems for each of five dimensions give number of 11111. It measure an individual's health related quality of life.
  • Change in Brain GSH levels [ Time Frame: Baseline and 12 months ]
    MRI will be used to measure GSH levels
Original Other Pre-specified Outcome Measures
 (submitted: August 22, 2016)
  • Change in Exercise Frequency [ Time Frame: Baseline and 12 months ]
    Exercise frequency will be measured using Sensewear physical activity monitoring device. This device is small and lightweight. It is worn around the upper left arm (touching the skin) for approximately 7 days during all waking and sleeping hours except bathing and showering.
  • Change in Exercise Duration [ Time Frame: Baseline and 12 months ]
    Exercise duration will be measured using Sensewear physical activity monitoring device. This device is small and lightweight. It is worn around the upper left arm (touching the skin) for approximately 7 days during all waking and sleeping hours except bathing and showering. The duration is measured in minutes.
  • Change in Exercise Intensity [ Time Frame: Baseline and 12 months ]
    Exercise intensity will be measured using Sensewear physical activity monitoring device. This device is small and lightweight. It is worn around the upper left arm (touching the skin) for approximately 7 days during all waking and sleeping hours except bathing and showering. Exercise intensity is based on MET levels that range from moderate to very vigorous.
  • Change in lower extremity performance [ Time Frame: Baseline and 12 months ]
    Short Physical Performance Battery (SPPB)
  • Change in functional fitness of basic activities of daily living [ Time Frame: Baseline and 12 months ]
    Senior Fitness Test
  • Change in health related quality of life [ Time Frame: Baseline and 12 months ]
    The 12-Item Short Form Survey (SF-12) is a practical, reliable, and valid measure of mental health and physical function.
  • Change in perceived stress [ Time Frame: Baseline and 12 months ]
    The Perceived Stress Scale (PSS) is one of the most widely used psychological instruments for measuring the perception of stress. It measures the degree to which situations in the participants life are gauged as stressful.
  • Change in quality of life [ Time Frame: Baseline and 12 months ]
    Investigators will use Satisfaction with Life Scale (SWLS) as global cognitive judgement of study participants Life Satisfaction which is one factor in the overall subjective well being.
  • Change in exercise self-efficacy [ Time Frame: Baseline and 12 months ]
    The investigators will use the Exercise Self-Efficacy Scale (EXSE) to assess the study participants belief in their ability to continue exercising three times a week at moderate intensity for 40 plus minutes a session in the future.
  • Change in mood [ Time Frame: Baseline and 12 months ]
    The Geriatric Depression Scale (GDS) will be used. It is an instrument used exclusively with older populations. The scale uses yes and no questions to gauge level of depression in the elderly.
  • Change in anxiety symptoms [ Time Frame: Baseline and 12 months ]
    Positive and Negative Affect Schedule (PANAS)
 
Descriptive Information
Brief Title  ICMJE Investigating Gains in Neurocognition in an Intervention Trial of Exercise
Official Title  ICMJE Investigating Gains in Neurocognition in an Intervention Trial of Exercise
Brief Summary This randomized control trial will examine whether a 12 month monitored exercise intervention improves brain health in cognitively normal older adults. This trial will also address several important unanswered questions: (1) Are the recommended public health guidelines of 150 minutes/week of exercise sufficient for improving cognitive performance? (2) Does exercise influence brain structure and/or function? (3) Is there a dose-response effect of exercise on the above variables such that greater amounts of exercise brings about greater benefits in cognitive and brain health? (4) What are the mechanisms by which exercise influences brain health? and (5) What factors attenuate or magnify the effects of exercise on brain and cognitive health and contribute to the individual variability in intervention outcomes?
Detailed Description

The investigators are conducting a 12-month, multi-site, randomized dose-response exercise trial (i.e., brisk walking) in 639 cognitively normal adults between 65-80 years of age. Participants will be randomized to a (a) moderate intensity aerobic exercise condition at the public health recommended dose of 150 minutes/week (N=213), (b) a moderate intensity exercise condition at 225 minutes/week (N=213), or (c) a light intensity stretching-and-toning control condition for 150 minutes per week (N=213). Participants will meet 3 days/week for site-based exercise and do home-based activity on two more days of the week for 12 months. A comprehensive state-of-the-science battery of cognitive, MRI, amyloid imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and quality of life measures will be assessed at baseline and after completion of the intervention.

Specific Aims include:

  1. Cognitive Enhancement: Using a comprehensive neuropsychological battery and the NIH Toolbox, the investigators will test (a) whether a 12-month moderate intensity exercise intervention improves cognitive performance in older adults and (b) whether the improvements occur in a dose-dependent manner. Hypothesis: PA will enhance cognitive performance non-uniformly with the greatest effects occurring for executive and declarative memory functions. The investigators also predict that these improvements will follow a dose-dependent trajectory with 225 minutes/week of PA demonstrating greater improvements than 150 minutes/week of PA.
  2. Brain Augmentation: The investigators will test (a) whether a 12-month PA intervention augments MRI markers of brain health and (b) whether changes happen in a dose-dependent manner. Hypothesis: PA will most profoundly influence the volume, microstructural white matter integrity, cerebral blood flow, and connectivity of regions supporting declarative memory (e.g., hippocampus) and executive function (e.g., prefrontal cortex; PFC). Further, the investigators predict that 225 minutes/week will result in greater effects than 150 minutes/week. The investigators predict that these changes in brain outcomes will mediate the cognitive improvements in Aim 1.
  3. Biomediators: The investigators will test the hypothesis that cardiometabolic, inflammatory, and neurotrophic changes mediate improvements in brain and cognition. Hypothesis: (1) decreases in pro-inflammatory cytokines, (2) decreases in central adiposity, arterial stiffness, and insulin resistance, and (3) increases in brain-derived neurotrophic factor (BDNF) levels will statistically mediate changes in cognitive performance (Aim 1) and brain health (Aim 2), and that the strength of this mediating relationship might vary as a function of certain apriori moderating variables of interest
  4. Moderators: To examine subgroups (i.e., individual differences) that attenuate or magnify the effect of the intervention on cognitive, brain, and physiological systems to better understand the factors that predict 'responders' versus 'non-responders' to the intervention. The investigators will examine three categories of variables: (1) demographic (e.g., age) (2) genetic (e.g., APOE), and (3) baseline Aβ burden. Hypothesis: The favorable effects of PA on brain and cognition will be greatest for older individuals with greater Aβ burden, and in those with a genetic susceptibility for accelerated cognitive decline.
  5. Amyloid Diminution: We will test (a) assess Amyloid deposition changes in response to physical activity and (b) whether changes occur in a dose-dependent manner and (c) examine baseline Amyloid as a moderator of intervention effects and (d) examine changes in Amyloid as a mediator of changes in brain and cognition. Hypothesis: We predict that Aβ burden will be attenuated over the course of the intervention for the aerobic exercise groups compared to control group. Further, we predict that 225 minutes/week of aerobic exercise will result in a greater effect on Aβ than 150 minutes/week
  6. Exploratory Aims: The investigators will explore (a) whether baseline brain health metrics predict adherence and compliance to 12-months of PA, and (b) the utility of multi-modal brain imaging analytical approaches to more comprehensively understand the effects of PA on the aging brain.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Study participants will be randomly assigned to one of three exercise intervention arms.
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE
  • Healthy
  • Cognitive Function 1, Social
Intervention  ICMJE
  • Behavioral: 150 Minutes Week
    This group will walk 150 minutes per week. Participants will have 3 supervised exercise sessions per week. A walking duration of 30 minutes will be achieved by the third week of the program and be maintained for the duration of the intervention. Heart rate will be monitored to ensure proper intensity levels. Participants will also be instructed to exercise at home for 30 minutes for two other days of the week at a similar intensity. The prescribed intensity will be 50-60% of the maximum heart rate reserve for weeks one to six and 60-75% for the remainder of the program. Participants in the walking conditions will wear heart rate monitors and be encouraged to walk within their target heart rate zone. During the current Covid-19 pandemic, all intervention exercise has been shifted to home based.
  • Behavioral: 225 Minutes Week
    This group will walk 225 minutes per week. Participants will have 3 supervised exercise sessions per week. A walking duration of 45 minutes will be achieved by the sixth week of the program. This will be maintained for the duration of the intervention and heart rate will be monitored to ensure proper intensity levels. Participants will be instructed to exercise at home for 45 minutes for two other days of the week at a similar intensity. The prescribed intensity will be 50-60% of the maximum heart rate reserve for weeks one to six and 60-75% for the remainder of the program. Participants in the walking conditions will wear heart rate monitors and be encouraged to walk within their target heart rate zone. During the current Covid-19 pandemic, all intervention exercise has been shifted to home based.
  • Behavioral: Stretch and Tone
    The control condition will focus on improving balance, flexibility, and strength. This group will meet for supervised sessions 3 times per week for 12 months. Resistance bands, balance disks, yoga blocks, and exercise mats will be used to engage in non-cardiorespiratory activities. These are progressive in nature and include modifications to accommodate injuries, physical difficulties, etc. A new set of similar, yet slightly more challenging activities will be introduced every four weeks. During the first two weeks, participants are introduced to the new activities, and, during the second two weeks, they are encouraged to increase intensity by using more weight or more repetitions. During the current Covid-19 pandemic, all intervention exercise has been shifted to home based.
Study Arms  ICMJE
  • Experimental: 150 Minutes Week
    Participants engage in supervised 12 month moderate intensity aerobic exercise intervention with goal of maintaining 150 minutes of exercise per week.
    Intervention: Behavioral: 150 Minutes Week
  • Experimental: 225 Minutes Week
    Participants engage in supervised 12 month moderate intensity aerobic exercise intervention with goal of maintaining 225 minutes of exercise per week.
    Intervention: Behavioral: 225 Minutes Week
  • Active Comparator: Stretch and Tone
    Participants engage in supervised 12 month non-cardiorespiratory activity intervention. This group has focus on improving balance, flexibility, and strength.
    Intervention: Behavioral: Stretch and Tone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 22, 2016)
639
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men and women 65 - 80 yrs
  • Ambulatory without pain or the assistance of walking devices
  • Able to speak and read English
  • Exercise level of <20 minutes per week
  • Medical clearance by PCP
  • Living in community for duration of the study
  • Reliable means of transportation
  • No diagnosis of a neurological disease
  • Eligible to undergo MRI

Exclusion Criteria:

  • Current diagnosis of a DSM-V Axis I or II disorder including Major Depression
  • History of major psychiatric illness including schizophrenia (not including general anxiety disorder or depression)
  • Current treatment for cancer - except non-melanoma skin
  • Neurological condition (MS, Parkinson's, Dementia, MCI) or brain injury (traumatic or Stroke)
  • Type I Diabetes or insulin-dependent diabetes
  • Current alcohol or substance abuse
  • Current treatment for congestive heart failure, angina, uncontrolled arrhythmia, DVT or other cardiovascular event
  • Myocardial infarction, coronary artery bypass grafting, angioplasty or other cardiac condition in the past year
  • Regular use of an assisted walking device
  • Presence of metal implants (pacemaker, stents) that would be MR ineligible
  • Claustrophobia
  • Color Blindness
  • Not fluent in English
  • Not medically cleared by PCP
  • Engaging in >20 minutes of moderate intensity physical activity
  • Traveling consecutively for 3 weeks or greater during the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years to 80 Years   (Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: George A Grove, MS 412-624-4556 ggrove@pitt.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02875301
Other Study ID Numbers  ICMJE 1R01AG053952( U.S. NIH Grant/Contract )
R01AG060050 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data from this study will be made available to outside investigators under a data-sharing agreement. The data will be available to outside investigators after publication of the primary aims and at completion of quality control assessments and data organization. The investigators expect that the data from this study will result in significant interest from internal and external investigators for secondary data analysis and ancillary project proposals, so the investigators will create an oversight committee made up of Principal and Co-Investigators for monitoring, approving, and disseminating the data along with monitoring data analysis plans and development of manuscripts. This is important for eliminating redundant analyses, results, or manuscripts.
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: Will be made available after study investigators have published summary data and primary aim results. Will be available for unlimited amount of time.
Access Criteria: Data requests will be approved by IGNITE Executive committee. Requests can be made by completing data request form
Responsible Party Kirk Erickson, PhD, University of Pittsburgh
Study Sponsor  ICMJE University of Pittsburgh
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Kirk I Erickson, PhD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP