We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exercise in Adults With Mild Memory Problems (EXERT)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02814526
Recruitment Status : Completed
First Posted : June 27, 2016
Last Update Posted : July 11, 2022
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Wake Forest University
Information provided by (Responsible Party):
Alzheimer's Disease Cooperative Study (ADCS)

Brief Summary:

This study evaluates the effects of physical exercise on cognition, functional status, brain atrophy and blood flow, and cerebrospinal fluid biomarkers of Alzheimer's disease in adults with a mild memory impairment.

Half of participants will participate in a stretching-balance-range of motion exercise program, while the other half will participate in a moderate/high aerobic training program.


Condition or disease Intervention/treatment Phase
Mild Cognitive Impairment Cognitive Decline Memory Impairment Behavioral: Aerobic exercise Behavioral: Stretching/balance/range of motion exercise Not Applicable

Detailed Description:

Overall Study Design:

The EXERT trial was a multicenter phase 3 randomized, single-blind study that examined the effects of aerobic exercise on cognition, functional status, whole and regional cerebral blood flow, and cerebrospinal fluid biomarkers of Alzheimer's disease in approximately 300 adults with amnestic MCI. EXERT included an 18-month behavioral intervention trial, with a 12-month supervised exercise intervention phase with its primary endpoints, followed by a 6-month unsupervised exercised phase.

Subject Populations and Group Assignments:

The study population included male and female subjects aged 65 to 89 diagnosed with test scores and clinical ratings consistent with amnestic Mild Cognitive Impairment (MCI).

Assignment to study groups:

involved randomization to either treatment or active control, and study staff performing assessments were blinded to intervention assignment to maintain the single-blind structure of the trial.

Participants were to complete EXERT interventions at participating YMCAs located near the selected clinic sites across the U.S. The YMCA provided 18-month memberships at no cost to participants. In the first 12 months, a study-certified YMCA Trainer supervised all participants for the first 8 exercise sessions completed (weeks 1 and 2), and for 2 of 4 weekly sessions thereafter through Month 12. At Month 12, participants transitioned to independent exercise and were instructed to continue their assigned exercise programs for the final 6 months of the study without supervision. To encourage adherence and optimize cost efficiency, Trainers provided supervision to small groups of participants (2-4 individuals) randomized to the same intervention whenever possible. Compliance was evaluated using multiple mechanisms including heart rate monitoring, participant ratings of perceived exertion, entries in participants' Physical Activity Logs, Trainer assessment of effort, and weekly data review by the YMCA-Project Manager (Y-PM) and the Intervention Oversight Team (includes the PDs, Wake Forest team of exercise trial specialists, and Y-USA). These mechanisms provided multiple and regular opportunities to discuss participant progress, identify and resolve barriers, and encourage high levels of adherence to study protocols. The Intervention Oversight Team had the necessary expertise to successfully accomplish this objective in EXERT.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 296 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Therapeutic Effects of Exercise in Adults With Amnestic Mild Cognitive Impairment
Actual Study Start Date : September 13, 2016
Actual Primary Completion Date : December 31, 2021
Actual Study Completion Date : January 28, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Aerobic
Moderate/high intensity aerobic exercise will involve training at 70-80% heart rate reserve for 30 min, with an additional 10 minutes for warm-up and 5 minutes for cool-down, 4 times per week, for 12 months while supervised twice per week by a study-certified trainer at a participating YMCA .
Behavioral: Aerobic exercise
Moderate/high intensity aerobic exercise will involve training at 70-80% heart rate reserve for 30 min, with an additional 10 minutes for warm-up and 5 minutes for cool-down, 4 times per week, for 12 months while supervised twice per week by a study-certified trainer at a participating YMCA .

Active Comparator: Stretching/balance/range of motion
The stretching/balance/range of motion program will involve exercise at or below 35% heart rate reserve for 30 min, with an additional 10 minutes for warm up and 5 minutes for cool-down, 4 times per week, for 12 months while supervised twice per week by a study-certified trainer at a participating YMCA.
Behavioral: Stretching/balance/range of motion exercise
The stretching/balance/range of motion program will involve exercise at or below 35% heart rate reserve for 30 min, with an additional 10 minutes for warm up and 5 minutes for cool-down, 4 times per week, for 12 months while supervised twice per week by a study-certified trainer at a participating YMCA.




Primary Outcome Measures :
  1. Cognitive function composite score (ADAS-Cog-Exec) [ Time Frame: 12 months ]
    To test the hypothesis that 12 months of supervised moderate/high intensity aerobic exercise, relative to a stretching/balance/range of motion control, improves cognitive function measured using the ADAS-Cog-Exec, in older adults with amnestic MCI.


Secondary Outcome Measures :
  1. Cognitive function composite score (ADAS-Cog-Exec) in a subset of participants who completed 12 months of the study prior to the COVID-19 pandemic score (ADAS-Cog-Exec) [ Time Frame: 12 Months ]
    To test the hypothesis that 12 months of aerobic exercise, relative to the control, improves scores on the primary outcome (ADAS-Cog-Exec) in the subset of participants who had the opportunity to complete a full 12 months of the study (i.e., 12 months of exercise and the 12 Month outcomes assessment) before the COVID-19 pandemic affected trial conduct.

  2. Executive Function and Episodic Memory composite scores [ Time Frame: 12 Months ]
    To test whether 12 months of supervised aerobic exercise, relative to the control, improves executive function and episodic memory measured by domain-specific composite scores

  3. Volumetric and arterial spin labeling magnetic resonance imaging (MRI) [ Time Frame: 12 Months ]
    To test whether 12 months of aerobic exercise, relative to the control, reduces brain atrophy and increases blood flow in the hippocampus and in prefrontal (superior frontal, caudal-middle frontal, rostral-middle frontal, pars opercularis, par triangularis) and AD signature (parahippocampus, fusiform, inferior temporal, middle temporal, inferior-parietal) composite regions, measured using volumetric and arterial spin labeling magnetic resonance imaging (MRI).

  4. AD biomarkers in CSF and blood [ Time Frame: 12 Months ]
    To test whether 12 months of aerobic exercise, relative to the control, favorably alters AD biomarkers in CSF (ab42/ab40, ab42/tau, ab42/p-tau) and blood (ab42/ab40).


Other Outcome Measures:
  1. Intervention effects on secondary outcomes in a subset of participants who completed 12 months of the study prior to the COVID-19 pandemic. [ Time Frame: 12 months ]
    To examine intervention effects on secondary outcomes listed above in participants who had the opportunity to complete a full 12 months of the study before the pandemic affected trial conduct.

  2. Exploratory magnetic resonance imaging (MRI) volumes and perfusion and individual AD biomarkers in CSF and blood measures [ Time Frame: 12 Months ]
    To test whether 12 months of aerobic exercise, relative to the control, favorably affects MRI whole brain, ventricular and entorhinal volumes; perfusion in whole brain, gray matter and white matter; and individual AD biomarkers in CSF (ab42, ab40, total tau, p-tau, BDNF) and blood (ab42, ab40).

  3. Clinical Dementia Rating Scale-Sum of Boxes (CDR) and Alzheimers Disease Assessment Scale-Cognitive 13-item (ADAS-Cog13) [ Time Frame: 12 Months ]
    To test whether 12 months of aerobic exercise, relative to the control, reduces clinical ratings of cognitive impairment as measured by the CDR Sum of Boxes, and total score on the ADAS Cog13.

  4. Measures of cognitive function and well-being including (1) ADCS-ADL-MCI); (2) BRIEF-A; (3) GDS; (4) NPI; SF-36; EuroQol: 5-Item Health Questionnaire; (5) CCI: Cognitive Change Index); and (6) Study Partner Self-Assessment [ Time Frame: 12 Months ]
    To test whether 12 months of aerobic exercise, relative to the control, improves self-report measures of cognitive function and well-being, including (1) daily living skills (ADCS-Activities of Daily Living-MCI); (2) BRIEF-A: Behavior Rating Inventory of Executive Function-Adult Version); (3) mood (GDS); (4) health-related quality of life (NPI: Neuropsychiatric Inventory; SF-36: 36-Item Short Form Health Survey; EuroQol: 5-Item Health Questionnaire); (5) subjective memory concerns (CCI: Cognitive Change Index); and (6) Study Partner Self-Assessment Questionnaire

  5. ADAS-Cog-Exec, Executive Function, and Episodic Memory Composites [ Time Frame: 18 Months ]
    To examine enduring cognitive effects (measured by ADAS-Cog-Exec, Executive Function and Episodic Memory Composites) of the intervention following a 6-month extension (through Month 18) when the prescribed exercise is continued without supervision.

  6. Subgroup treatment responder analyses [ Time Frame: 12 Months ]
    To explore whether sex, age, baseline AD biomarker profile in CSF (ab42/ab40, ab42/tau, ab42/p-tau) and blood (ab42/ab40), and ApoE4 genotype (e4+, e4-) predict treatment response.



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.


Layout table for eligibility information
Ages Eligible for Study:   65 Years to 89 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age between 65 and 89 years old, inclusive
  2. MMSE: ≥24 for participants with 13 or more years of education; ≥22 for participants with 12 or fewer years of education
  3. Global CDR score of 0.5 with a memory score of at least 0.5
  4. Profile of test scores and clinical ratings is consistent with amnestic mild cognitive impairment
  5. Speaks English fluently
  6. Visual and auditory acuity adequate for cognitive testing
  7. Completed at least 6 years of formal education or work history sufficient to exclude mental retardation
  8. Has an informant who knows the participant well, has regular contact, and is available to accompany the participant to clinic visits or complete study partner assessments remotely.
  9. Sedentary or underactive, determined by responses to the staff-administered EXERT Telephone Assessment of Physical Activity (TAPA) survey
  10. Willing to be randomized to either intervention group and to complete the assigned activities as specified for 18 months
  11. Willing and able to reliably travel to the identified YMCA, 4 times per week for 18 months
  12. Ability to safely participate in either intervention and complete the 400 m Walk Test within 15 min without sitting or use of any assistance
  13. Plans to reside in the area for at least 18 months
  14. For planned travel, total time away must be no more than 2 months over the course of the study, and no more than 1 month at any one time; participants must be willing to continue the assigned exercise program if travelling out of the area for more than 1 week
  15. In overall good general health with no disease or planned surgery that could interfere with study participation
  16. Modified Hachinski ≤4
  17. Stable use of cholinesterase inhibitors, memantine, vitamin E, estrogens, aspirin (81 300 mg daily), beta-blockers, or cholesterol-lowering agents for 12 weeks prior to screening (important for biomarker analyses)
  18. Stable use of antidepressants lacking significant anticholinergic side effects for 4 weeks prior to screening as long as the participant does not meet DSM V criteria for major depression currently or in the last 12 months; GDS scores are to be used to inform clinical decisions but there is no specified cut-off score for inclusion
  19. When applicable, willing to complete 4-week washout of psychoactive medications, including disallowed antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, and willing to avoid these medications for the duration of the trial
  20. Able to complete all baseline assessments

Exclusion Criteria

  1. Any significant neurologic disease, other than MCI, including any form of dementia, Parkinsons disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities
  2. Sensory or musculoskeletal impairment sufficient to preclude successful and safe completion of the intervention or assessment protocols; must be able to walk safely and unassisted on a treadmill
  3. Contraindications for MRI studies, including claustrophobia, metal (ferromagnetic) implants, or cardiac pacemaker
  4. Brain MRI at screening shows evidence of infection, infarction, or other clinically significant focal lesions, including multiple lacunes in prefrontal or critical memory regions; inconclusive findings may be subject to review by the ADCS Imaging Core
  5. History of major depression or bipolar disorder (DSM V criteria), psychotic features, agitation or behavioral problems within the last 12 months
  6. History of schizophrenia, as per DSM V criteria
  7. History of alcohol or substance abuse or dependence within the past 2 years, as per DSM V criteria
  8. Currently consumes more than 3 alcoholic drinks per day
  9. Clinically significant or unstable medical condition, including uncontrolled hypertension or significant cardiac, pulmonary, hematologic, renal, hepatic, gastrointestinal, endocrine, metabolic or other systemic disease in the opinion of clinic medical personnel that may put the participant at increased risk, influence the results or compromise the participants ability to participate in the study (treated atrial fibrillation for more than 1 year or occasional premature ventricular contractions on ECG are not exclusions)
  10. History in the last 6 months of myocardial infarction, coronary artery angioplasty, bypass grafting, or STENT placement
  11. History in the last 3 months of transient ischemic attack or small vessel stroke (if more than 3 months, small vessel stroke with no residual effects are permitted)
  12. Expected joint replacement surgery within the next 18 months
  13. History within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen posttreatment
  14. Hemoglobin A1c >7.0
  15. Clinically significant abnormalities in screening laboratory blood tests: low B12 is exclusionary, unless follow-up labs (homocysteine [HCY] and methylmalonic acid [MMA]) indicate that it is not physiologically significant
  16. Current or past use of insulin to treat type 2 diabetes (other diabetes medications are acceptable if hemoglobin A1c ≤7)
  17. Current use (within 60 days of screening) of psychoactive medications including tricyclic antidepressants, antipsychotics, mood-stabilizing psychotropic agents (e.g. lithium salts), psychostimulants, opiate analgesics, antiparkinsonian medications, anticonvulsant medications (except gabapentin and pregabalin for non-seizure indications), systemic corticosteroids, or medications with significant central anticholinergic activity. Limited use of antipsychotics (quetiapine ≤ 50mg/day or risperidone ≤ 0.5mg/day), and non-chronic use of opiate analgesics on an as needed basis is permitted; such medications must be avoided for 8 hours before clinic assessments
  18. Chronic use of anxiolytics or sedative hypnotics except as follows: use of benzodiazepines for treatment on an as-needed basis for insomnia or daily dosing of anxiolytics is permitted; medications must be avoided for 8 hours before clinic assessments
  19. Previous or current treatment involving active immunization against amyloid
  20. Previous treatment with approved or investigational agents with anti-amyloid properties or passive immunization against amyloid are prohibited 12 months prior to screening and for the duration of the trial; treatment with other investigational agents are prohibited 3 months prior to screening and for the duration of the trial
  21. For LP, current use of anticoagulants such as Coumadin, Plavix, or high dose Vitamin E
  22. For LP, current blood clotting or bleeding disorder, or significantly abnormal prothrombin time (PT) or partial thromboplastin time (PTT) at screening
  23. For LP, presence of physical distortions due to spinal surgery, severe degenerative joint disease or deformity, or obesity that could interfere with CSF collection (as per investigator judgment)
  24. Participants whom the PI deems otherwise ineligible

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): NCT02814526


Locations
Layout table for location information
United States, California
University of California, Irvine
Irvine, California, United States, 92697
VAPAHCS / Stanford University School of Medicine
Palo Alto, California, United States, 94304
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30329
United States, Illinois
Great Lakes Clinical Trials (Andersonville)
Chicago, Illinois, United States, 60640
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66205
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Nevada
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, United States, 89106
United States, New York
New York University Medical Center
New York, New York, United States, 10016
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Texas
University of North Texas Health Science Center
Fort Worth, Texas, United States, 76107
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Alzheimer's Disease Cooperative Study (ADCS)
National Institute on Aging (NIA)
Wake Forest University
  Study Documents (Full-Text)

Documents provided by Alzheimer's Disease Cooperative Study (ADCS):
Study Protocol  [PDF] November 18, 2021
Statistical Analysis Plan  [PDF] February 3, 2022
Informed Consent Form  [PDF] May 28, 2019

Publications of Results:
Other Publications:

Layout table for additonal information
Responsible Party: Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier: NCT02814526    
Other Study ID Numbers: ADC-041-EX
U19AG010483-22 ( U.S. NIH Grant/Contract )
First Posted: June 27, 2016    Key Record Dates
Last Update Posted: July 11, 2022
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Data sharing is integral to the ADCS's mission to develop and execute innovative clinical trials focused on interventions that may prevent, delay, or treat the expression of Alzheimer's disease and related dementias. The ADCS is committed to sharing resources and tools, including data, biospecimens, trial designs, outcome and analysis measures following NIH guidelines.

DATA SHARING: The ADCS Data and Sample Sharing Committee (DSSC) grants access to de-identified data to individuals who complete the request process and agree to the conditions in an ADCS/UCSD Data Use Agreement (DUA). After approval and receipt of the fully executed DUA, applicants are authorized to acquire data. Non-compliance with the DUA, including the requirement to provide requested updates will jeopardize further access to data.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: 01 March 2023
Access Criteria: Data requestors must complete an ADCS data and sample sharing request form. Upon approval, requestors must complete a data use agreement prior to accessing the data.
URL: https://www.adcs.org/data-sharing/
Keywords provided by Alzheimer's Disease Cooperative Study (ADCS):
exercise
Additional relevant MeSH terms:
Layout table for MeSH terms
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders