Genes, Exercise, Neurocognitive and Neurodegeneration: Community-Based Approach

NCT02614365 | Unknown DMC

• 1 other identifier: 07-MED-41E
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Whereas the advantageous effects of exercise-training on memory is increasingly recognized, the practicality and clinical usefulness of such interventions in community-dwelling older African Americans (AA)s Mild Cognitively Impaired (MCI) subjects, and the mechanism by which an effect occurs need elucidation. Because aerobic-exercise can improve emerging cardiovascular (CVD)-related risk factors for cognitive decline such as lipids, inflammatory cytokines and glucose homeostasis; the Investigators will examine training effects on these and related biomarkers. The imperative for this study is further underscored by the fact that, AAs: i) have high rates of dementia, and ii) have paucity of cross-sectional, and lack prospective data on the effects of exercise on cognition. To overcome barriers to recruitment and retention, enhance compliance with a long exercise program (3-times/week), and maximize the use of available resources, the Investigators will use a community-based approach. Therefore, the primary objectives of this study build on the Investigators' experience, and will compare the effects of aerobic-exercise to stretch-exercise (control) in community-dwelling AA MCI subjects. Following the initial 6 months active intervention, the aerobic-exercise group will follow a prescribed but free living 40 minutes, 3 time/week exercise regimen while the control group returns to usual care plus stretch-exercise for additional 12 months. This study will facilitate the estimation of sample size for a larger confirmatory study in AAs. A newly acquired direct oversight of the DC Ward-6 Senior Wellness Center and its infrastructures by the Howard University Division of Geriatrics will provide additional resources and access to the community. In addition to the Investigator's feasibility aims, the Investigators will determine performance on cognitive tasks using the Alzheimer's Disease Assessment Scale-Cognitive Sub-scale (ADAS-Cog) and Clinical Dementia Rating Scale (CDR) sum of boxes supplemented by tests of executive function (EF) and Functional Activity Questionnaire (FA) and together as ADAS-Cog-Plus; changes in brain volume regions of interest (ROI) with Magnetic Resonance Imaging (MRI), selected CVD and AD-related bio-markers.

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Neuropsychological assessments

  Neuropsychological battery will be used to assess cognitive domains of interest.

  Change cognitive measures from baseline at 6 month

Secondary Outcomes (10)

• Brain MRI-derived regions of interest assessed by change in regions of interest brain volume

  Change in regions of interest brain volume from baseline at 6 month and 12 month

• Cardiovascular disease-related markers and biomarkers assessed by change in lipids (mg/dl)

  Change in lipids (mg/dl) from baseline at 3 month, 6 month, 9 month, 12 month and 18 month

• Cardiovascular disease-related markers and biomarkers assessed by change in Nuclear Magnetic Resonance Spectroscopy measured lipids concentrations (nml/L)

  Change in Nuclear Magnetic Resonance (NMR) Spectroscopy measured lipids concentrations (nml/L) from baseline at 3 month, 6 month, 9 month, 12 month and 18 month

• Cardiovascular disease-related markers and biomarkers assessed by change in cytokines' levels (pg/ml)

  Change in cytokines' levels (pg/ml) from baseline at 3 month, 6 month, 9 month, 12 month and 18 month

• Alzheimer's disease-related markers and biomarkers assessed by change in serum levels of Tau (ng/L) and Abeta (ng/L)

  Change in serum levels of Tau (ng/L) and Abeta (ng/L) from baseline to 3 month, 6 month, 9 month, 12 month and 18 month

Study Arms (2)

Aerobic Exercise

EXPERIMENTAL

6-month 3-time/week aerobic exercise, and a 12-month passive follow-up.

Behavioral: Aerobic exercise

Stretch Exercise

ACTIVE COMPARATOR

6-month 3-time/week stretch exercise, and a 12-month passive follow-up.

Behavioral: Stretch exercise

Interventions

Aerobic exercise BEHAVIORAL

Cardiovascular fitness

Aerobic Exercise

Stretch exercise BEHAVIORAL

Muscle stretch

Stretch Exercise

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 55 years
• Ability to exercise vigorously without causing harm to self
• Have Mild Cognitive Impairment (MCI) as defined under diagnosis above
• Have a study partner
• Be in good general health
• Willing to exercise for 12 months
• Willingness to undergo neuropsychological evaluation, PET scan of the brain, and have blood drawn

You may not qualify if:

• Age younger than 55 years
• Scored below 24 on the MMSE (have dementia)
• Have a Body Mass Index (BMI) ≥35,
• If a woman and peri-menopausal and unwilling to maintain current hormone replacement therapy status and allowed medication usage during the study.
• To avoid inaccurate HDL and HDL2-C determinations or avoid bias from familial hypercholesterolemia, respectively, participants with TG \>400 mg/dl and those whose LDL-C levels \>95% or HDL levels \<10% of age and sex-adjusted norms will be excluded.
• Excluded medications: Medications with significant effect on memory such as anticholinergic (diphenhydramine, tricyclic antidepressants, benztropine); sedative hypnotics such as benzodiazepines; narcotics; and antiparkinsonian medications will all be excluded.
• Unstable medical conditions indicated by starting new medications within 6 weeks of enrollment will be disallowed.
• Concomitant Medication: Medications used in the therapy of AD (Reminyl, Aricept, Exelon, Namenda, Gingko Biloba) will be allowed if stable on these medications for 6 weeks prior to enrollment.
• Excluded Medical Diagnosis: To avoid misclassification bias, the Investigator will exclude persons with neurological, psychiatry or other clinical conditions likely to cause dementia. Participants having functional limitation preventing vigorous exercise, chronic disabling diseases, and alcoholism and drug abuse will be excluded.
• Clinically significant cerebrovascular disease including cortical infarct, strategically located subcortical gray matter or extensive white matter abnormalities.

Sponsors & Collaborators

• Howard University: lead
• University of Southern California: collaborator
• University of California, San Diego: collaborator

Study Sites (1)

Howard University Clinical Research Unit

Washington D.C., District of Columbia, 20060, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Exercise; Plyometric Exercise

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human

Study Officials

• Thomas O Obisesan, MD, MPH

  Howard University

  PRINCIPAL INVESTIGATOR

• Oyanumo Ntekim, MD

  Howard University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2015
• First Posted: November 25, 2015
• Study Start: July 1, 2014
• Primary Completion: April 1, 2022
• Study Completion: December 1, 2022
• Last Updated: March 2, 2021

Record last verified: 2021-03

Locations

US (1)