Pilot Study of Aerobic Exercise in Early Alzheimer's Disease(AD)

• ClinicalTrials.gov Identifier: NCT01128361
• Recruitment Status: Completed
• First Posted: May 21, 2010
• Results First Posted: March 13, 2017
• Last Update Posted: March 13, 2017
• Sponsor: Jeff Burns, MD
• Information provided by (Responsible Party): Jeff Burns, MD, University of Kansas Medical Center

Tracking Information

• First Submitted Date: May 18, 2010
• First Posted Date: May 21, 2010
• Results First Submitted Date: January 22, 2017
• Results First Posted Date: March 13, 2017
• Last Update Posted Date: March 13, 2017
• Study Start Date: May 2010
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 22, 2017)

• Memory Composite [ Time Frame: week 0, 13, and 26 ]
  A composite measure of several memory tests (Logical Memory (Immediate and Delayed), Free and Cued Selective Reminding Test (sum of free recall). Each score was normalized to an independent dataset of individuals without dementia. Then the 4 standardized scores were averaged. Numbers closer to positive indicate better memory performance. The scores are centered around a mean of 0 and standardized so each value represents a fraction of the standard deviation. There are no limits to the scores.
• Executive Function Composite [ Time Frame: Week 0, 13, and 26 ]
  A composite measure of several memory tests (Logical Memory (Immediate and Delayed), Free and Cued Selective Reminding Test (sum of free recall). Each score was normalized to an independent dataset. Then the 4 standardized scores were averaged. Numbers closer to positive indicate better executive function performance. . The scores are centered around a mean of 0 and standardized so each value represents a fraction of the standard deviation. There are no limits to the scores.
• Disability Assessment for Dementia [ Time Frame: Week 0, 13, and 26 ]
  This is a validated measure of disability for individuals with dementia. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability.
• Cornell Scale for Depression in Dementia [ Time Frame: Week 0, 13, and 26 ]
  The Cornell Scale for Depression in Dementia is a validate measure of depressive symptoms in individuals with dementia. Larger numbers indicate greater levels of depression. Scores range from 0 to 38.

• Original Primary Outcome Measures (submitted: May 20, 2010): Measure the effects of aerobic exercise Cognitive Outcomes for AD patients. [ Time Frame: week 0, 13, and 26 ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: May 20, 2010): Measure the effects of aerobic fitness on daily functions and behavior in early AD. [ Time Frame: week 0, 13, and 26 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pilot Study of Aerobic Exercise in Early Alzheimer's Disease(AD)
• Official Title: Alzheimer's Disease Exercise Prevention Trial
• Brief Summary: The current project is a natural extension of a programmatic line of investigation into the relationship between exercise, brain aging, and AD that Dr. Burns has developed over the last four years. The current study will provide data to estimate expected effect sizes for power analyses and sample size calculations. It will also provide an opportunity to optimally design a larger trial that can be extended to multiple sites to more definitively examine the role of exercise as a therapy in AD. The current project's aims are an important and necessary developmental step given the lack of fitness data in AD and the limited knowledge of the mechanisms that may form the basis of an association between aerobic fitness and AD.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• Behavioral: Aerobic Exercise
  Participants randomized to this group will perform 150 minutes a week of aerobic exercise over 3-5days. Participants will begin exercising 3 times the first week for 20 minutes, increasing to three bouts of 25 minutes the second week. Thereafter, weekly exercise duration will be increased until their target duration of 150 minutes is achieved in week 6. Exercise trainers will assist participants in adjusting exercise routines to achieve their weekly exercise duration goals. Use of equipment, achievement of target HR and safety will be closely monitored by the trainer through the course of the study. Each subject will wear a Polar F4 heart monitor (Polar USA) for recording heart rate during each exercise session. Subjects unable to exercise continuously on the treadmill will perform intermittent training until the target duration is reached. The majority of the exercise sessions will involve walking on a treadmill.
• Behavioral: Stretching
  This groups intervention is designed to match the aerobic exercise intervention with respect to participation and socialization. Stretching and toning has been repeatedly used as control intervention for exercise studies.The schedule and format will be identical to the aerobic conditioning group to best balance confounding variables such as attention, social interactions, and other unknown variables that might influence the results. An experienced and trained exercise instructor will run the stretching sessions three days a week at the local YMCA. We will monitor changes in heart rate with Polar F4 heart monitors (Polar USA) during the sessions to assess, and minimize, potential aerobic benefits from the intervention.

Study Arms

• Experimental: Aerobic Exercise
  Intervention: Behavioral: Aerobic Exercise
• Active Comparator: Stretching
  Intervention: Behavioral: Stretching

• Publications *: Morris JK, Vidoni ED, Johnson DK, Van Sciver A, Mahnken JD, Honea RA, Wilkins HM, Brooks WM, Billinger SA, Swerdlow RH, Burns JM. Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial. PLoS One. 2017 Feb 10;12(2):e0170547. doi: 10.1371/journal.pone.0170547. eCollection 2017.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2017): 76
• Original Estimated Enrollment (submitted: May 20, 2010): 80
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Informed consent provided by the participant or the participant's legally acceptable representative
• Age 55 years or older
• Diagnosis of Probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)
• Clinical Dementia Rating (CDR) of 0.5 (very mild) or 1 (mild dementia)
• Mini-Mental Status Exam Score of 16 to 30, inclusive.
• Rosen Modified Hachinski score of 4 or less
• Community dwelling with a caregiver able and willing to accompany the participant on all visits, if necessary. The caregiver must visit with the subject more than five times a week for the duration of the study.
• Underactive or sedentary as determined by a Telephone Assessment of Physical Activity.
• Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments
• Stable doses of medications for at least 30 days prior to screening. Cholinesterase inhibitors and memantine are allowed provided the participant is on stable doses without clinically significant side effects for 60 days. Additionally, the participant and caregiver will agree, barring unforeseen circumstances, to continue the same regimen for the trial duration.
• Likely to participate in all scheduled evaluations and complete the 26 week program.

Exclusion Criteria:

• CDR 0.5 uncertain dementia (i.e., not meeting NINCDS-ADRDA criteria).
• Significant neurological disease, other than AD, that may affect cognition
• MRI or CT scan indicative of significant abnormalities that may explain cognitive decline (e.g., multiple lacunar infarcts or a single prior infarct > 1 cm3, micro-hemorrhages or evidence of a prior hemorrhage > 1 cm3, evidence of cerebral contusion, encephalomalacia, aneurysm, vascular malformation, or space-occupying lesion such as an arachnoid cyst or brain tumor)
• Current clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to DSM-IV criteria or significant psychiatric symptoms (e.g., hallucinations) that could impair the completion of the study. Individuals with depressive symptoms (Geriatric Depression Scale < 6) and who do not meet criteria for major depression will be eligible.
• Current clinically-significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study
• History of clinically-evident stroke
• Clinically-significant infection within the last 30 days
• Myocardial infarction or symptoms of coronary artery disease (e.g., angina) in the last two-years.
• Uncontrolled hypertension within the last 6 months
• History of cancer within the last 5 years (except non-metastatic basal or squamous cell carcinoma)
• History of drug or alcohol abuse as defined by DSM-IV criteria within the last 2 years
• Presence of contraindications for MRI scanning (pacemaker, aneurysm clips, artificial heart valves, metal fragments, foreign objects) or claustrophobia
• Insulin-dependent diabetes mellitus
• Significant pain or musculoskeletal disorder that would prohibit participation in an exercise program

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01128361
• Other Study ID Numbers: 11969
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jeff Burns, MD, University of Kansas Medical Center
• Original Responsible Party: Jeffery Burns, MD, University of Kansas Medical Center
• Current Study Sponsor: Jeff Burns, MD
• Original Study Sponsor: University of Kansas
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jeffrey Burns, MD; University of Kansas Medical Center

• PRS Account: University of Kansas Medical Center
• Verification Date: January 2017