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Completed

NCT Number: NCT04848038

Combined Exercise Trial

The number of older Americans will double in the next 4 decades to nearly 90 million, placing an unprecedented financial and resource burden on the health care system. Exercise has clear and demonstrable physical benefits, but a more precise understanding of how exercise supports cognitive function is essential. Demonstrating definitively that exercise as recommended by public health entities has benefits for cognition would have enormous public health implications, encourage the public to adapt more active lifestyles, and stimulate the development of effective exercise delivery programs.

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Key information

Conditions

Age range

65 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Kansas Alzheimer's Disease Center

Fairway, Kansas, 66205, United States

About this study

Older adults often experience physical decline that can be directly ameliorated by physical activity and exercise. Evidence is building that exercise prevents cognitive decline or delays the onset of debilitating dementia (e.g. Alzheimer's disease) yet, the optimal dose and combination of exercise modalities for promoting brain health, however, remains unknown and essentially untested.

The long-term research goal of this project is to develop and test strategies to support successful aging and prevent Alzheimer's disease. The study will enroll 280 individuals, age 65 to 80 years without cognitive impairment, into a 26-week exercise intervention to test the combined and independent effects of aerobic and resistance training on cognition, brain structure, and physical function. The project will also explore underlying biological mechanisms that may link exercise with brain health.

Participants will be randomized into 1 of 4 groups: flexibility, toning and balance (control), aerobic exercise training, progressive resistance training, or combined aerobic and resistance training. All intervention groups represent the most common modalities of exercise and directly reflect the public health recommendations for aerobic and resistance training. Exercise training will occur in a community setting through the network of Greater Kansas City Young Men's Christian Association. It is hypothesized that 26 weeks of exercise will improve 1) cognitive performance, 2) regional brain volume, 3) cardiorespiratory fitness and strength 4) biomarkers.

This will be the largest study to assess the combined and independent effects of the two most recommended forms of exercise. Demonstrating specific exercise effects on cognitive function and brain health in older adults would have enormous public health implications. The study's results will also impact public health policy and education by providing evidence towards the specific or synergistic effects of aerobic and resistance training on cognition and brain structure. Encouraging the public to adapt more active lifestyles and stimulate the development of effective exercise delivery programs to enhance initiation and maintenance of physical activity interventions is key to increasing the number of quality years of life for America's aging population.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 65-80 yrs (inclusive at time of consent).
  • Conversant English speaking and reading ability.
  • Medical clearance by a health care provider.
  • Reliable means of transportation.
  • Telephone Interview of Cognitive Status score > 25 and adjudication of normal cognition based on cognitive test data by a study medical monitor.

Exclusion criteria

  • Intention to move out of the area or travel for more than 4 weeks in the next year.
  • Use of an assistive device for ambulation.
  • Joint pain severe enough to prevent taking walks in community, lifting objects over your head due to pain or restriction of movement, or that is worsened by increasing physical activity.
  • Any MRI contraindications or refusal to attempt MRI.
  • Treatment for alcohol or substance abuse in the last 2 years.
  • Treatment for cancer (other than non-metastatic, localized cancer) in the last 2 years.
  • Currently taking insulin.
  • Diagnosis of heart disease, heart failure, heart attack, or heart surgery or chest pain with effort in the last 2 years.
  • Untreated atrial fibrillation, valve replacements, angioplasty or stent placement in the last 2 years regardless of physician clearance.
  • History of major psychiatric illness including schizophrenia (not including general anxiety disorder or depression), multiple sclerosis, Parkinson's, Dementia, mild cognitive impairment, brain injury (traumatic or clinically evident Stroke), or similar, likely to negatively impact cognitive testing.
  • Head injury with loss of consciousness for more than a few minutes.
  • Change in blood pressure medication in the last 2 months.
  • Considered "Active" or engaging in a progressive resistance training 2 or more times a week.
  • reported condition likely to compromise ability to safely perform exercise as determined by study medical monitor (e.g. chronic obstructive pulmonary disease, Lupus, end stage renal disease, etc.)

Treatment and study plan

Exercise

Behavioral

Standard public health exercise recommendations

Other names: Weight Training, Aerobic Exercise, Progressive Resistance Exercise, Cross Training

Primary outcomes

  1. Global Cognition

    Time frame: Baseline, 6 months, 12 months

    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 a global cognition score derived from domains of cognition (e.g. Executive Function, Visuospatial Processing, Episodic Memory, Processing Speed). We will use a second order confirmatory factor analysis (CFA) to estimate the factor loadings between the observed indicators and the first order factors and between the first and second order factors. The CFA will use baseline data to avoid any potential intervention related biases. The primary outcome will be constructed by summing the weighted average (by the estimated first and second order loadings) of the standardized observed scores across the cognitive tests.

Secondary outcomes

  1. Hippocampal volume

    Time frame: Baseline, 12 months

    Volume of bilateral hippocampus in milliliters

  2. Peak oxygen consumption

    Time frame: Baseline, 12 months

    Peak volume of oxygen used in in milliliters per kilogram of body mass per minute during a graded maximal exercise test

  3. 1-Repetition Maximum

    Time frame: Baseline, 12 months

    The maximum amount of mass that can be lifted one time (summed leg press and chest press)

Other outcomes

  1. Wechsler Test of Adult Reading

    Time frame: Baseline

    The Wechsler Test of Adult Reading is a reading recognition test that can be used to estimate intelligence quotient and memory scores

  2. Hopkins Verbal Learning Test - Revised

    Time frame: Baseline, 6 months, 12 months

    The Hopkins Verbal Learning Test - Revised is an oral test that has been validated within brain-disordered populations (e.g., Alzheimer's disease, amnestic disorders) as a measure of verbal learning and memory.

  3. NIH Toolbox Flanker Task

    Time frame: Baseline, 6 months, 12 months

    The NIH ToolboxFlanker Task is a computer based test to assess selective attention and inhibitory function.

  4. NIH Toolbox Dimensional Change Card Sort

    Time frame: Baseline, 6 months, 12 months

    The NIH Toolbox Dimensional Change Card Sort is a computer based test to assess cognitive flexibility and attention.

  5. NIH Toolbox Oral Symbol Digit Test

    Time frame: Baseline, 6 months, 12 months

    The NIH Toolbox Oral Symbol Digit Test is a computer based test to Measure of processing speed.

  6. Virginia Cognitive Aging Project Logical Memory

    Time frame: Baseline, 6 months, 12 months

    The Virginia Cognitive Aging Project Logical Memory test measures episodic verbal memory.

  7. Spatial Relations

    Time frame: Baseline, 26-weeks, 52-weeks

    In this computer task, participants are asked to determine which three-dimensional figure can be formed from a two-dimensional pattern presented. This task measures visual construction ability.

  8. Letter Comparison

    Time frame: Baseline, 6 months, 12 months

    This paper-based task measures processing speed.

  9. Matrix Reasoning

    Time frame: Baseline, 6 months, 12 months

    This computer-based task measures visuospatial ability.

  10. Task Switching

    Time frame: Baseline, 6 months, 12 months

    This computer task asks participants to learn two different tasks. This task measures task switching.

  11. Spatial Working Memory

    Time frame: Baseline, 6 months, 12 months

    This computer task measures spatial memory.

  12. Stroop Task

    Time frame: Baseline, 6 months, 12 months

    This paper-based oral task measures executive control, specifically attention and inhibitory control.

  13. Fat Mass

    Time frame: Baseline, 12 months

    Estimated total body, axial, appendicular and visceral fat mass from dual x-ray absorptiometry.

  14. Lean Mass

    Time frame: Baseline, 12 months

    Estimated total body, axial, appendicular lean mass from dual x-ray absorptiometry.

  15. Bone Mass

    Time frame: Baseline, 12 months

    Estimated total body, axial, appendicular bone mass and density from dual x-ray absorptiometry.

  16. Cerebral brain blood flow

    Time frame: Baseline, 12 months

    Whole brain and regional cerebral blood flow estimated using arterial spin labeling, a technique of magnetic resonance imaging

  17. Senior Fitness Test

    Time frame: Baseline, 12 months

    Composite and sub-test scores of 6 common physical activities. Scores can be normalized for age and sex

  18. Waist to Hip Ratio

    Time frame: Baseline, 12 months

    The circumference of the waist and hip areas are measured via measuring tape.

  19. Body Mass Index

    Time frame: Baseline, 12 months

    Height and body mass are measured and Body Mass Index is calculated based on a standard equation.

  20. Blood lactate concentration

    Time frame: Baseline, 12 months

    Blood lactate concentration is measured before and after a bout of exercise.

  21. MacArthur Scale of Subjective Social Status

    Time frame: Baseline, 6 months, 12 months

    The MacArthur Scale of Subjective Social Status (MacArthur Socio-Economic Status Scale) contains questions regarding finances, assets and other home socioeconomics.

  22. Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognitive Abilities v1.0

    Time frame: Baseline, 6 months, 12 months

    Computer-based adaptive questionnaire of self-rated cognitive function.

  23. Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognitive General Concerns v1.0

    Time frame: Baseline, 6 months, 12 months

    Computer-based adaptive questionnaire of self-rated cognitive concerns.

  24. Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety v1.0

    Time frame: Baseline, 6 months, 12 months

    Computer-based adaptive questionnaire of self-rated anxiety.

  25. Patient-Reported Outcomes Measurement Information System (PROMIS) Depression v1.0

    Time frame: Baseline, 6 months, 12 months

    Computer-based adaptive questionnaire of self-rated depression.

  26. Patient-Reported Outcomes Measurement Information System (PROMIS) Ability to Participate in Social Roles and Activities v1.0

    Time frame: Baseline, 6 months, 12 months

    Computer-based adaptive questionnaire of self-rated social roles.

  27. Patient-Reported Outcomes Measurement Information System (PROMIS) General Life Satisfaction v1.0

    Time frame: Baseline, 6 months, 12 months

    Computer-based adaptive questionnaire of self-rated life satisfaction.

  28. Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function v1.0

    Time frame: Baseline, 6 months, 12 months

    Computer-based adaptive questionnaire of self-rated life physical function.

  29. Pittsburgh Sleep Quality Index

    Time frame: Baseline, 6 months, 12 months

    Paper-based questionnaire of self-rated sleep quality.

  30. Perceived Stress Scale, 10-item

    Time frame: Baseline, 6 months, 12 months

    Paper-based questionnaire of self-rated appraisal of stress.

  31. EuroQol Group Five Dimension Five Level (EQ-5D-5L)

    Time frame: Baseline, 6 months, 12 months

    A visual analog scale of quality of life

  32. National Health and Nutrition Examination Survey Diet Survey Questionnaire

    Time frame: Baseline, 6 months, 12 months

    Self-rated computer based questionnaire of dietary intake.

  33. Mediterranean Eating Pattern for Americans

    Time frame: Baseline, 6 months, 12 months

    Self-rated computer based questionnaire of mediterranean diet eating pattern.

  34. Barriers Self-Efficacy Scale

    Time frame: Baseline, 3 months, 6 months, 12 months

    Self-rated computer based questionnaire of physical activity self-efficacy.

  35. Exercise Self-Efficacy Scale

    Time frame: Baseline, 3 months, 6 months, 12 months

    Self-rated computer based questionnaire of exercise goal self-efficacy.

  36. Leisure Self-Efficacy Scale

    Time frame: Baseline, 3 months, 6 months, 12 months

    Self-rated computer based questionnaire of leisure-time physical activity self-efficacy.

  37. Physical Activity Self-Regulation Scale, 12-item

    Time frame: Baseline, 3 months, 6 months, 12 months

    Self-rated computer based measure of physical activity self-regulation for use with older adults.

  38. Godin Leisure-Time Exercise Questionnaire

    Time frame: Baseline, 3 months, 6 months, 12 months

    Self-rated computer based measure of use of leisure-time for physical activity

  39. Blood biomarkers

    Time frame: Baseline, 6 months, 12 months

    Brain Derived Neurotrophic factor , Insulin Growth Factor-1 (IGF-1), lactate, glucose and insulin levels, inflammatory cytokines, plasma phosphorylated tau (various form), plasma beta-amyloid (various forms), neurofilament light, glial fibrillary acidic protein and others as become available.

Sponsors and collaborators

Lead sponsor

University of Kansas Medical Center

Other

Registry information

Official study title

Differential Effects of Exercise Modality on Cognition and Brain in Older Adults

Acronym: COMET

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Apr 19, 2021
Registry last updated
Jun 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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