Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Mars Flavonol Exercise and Cognitive Function Study

This study has been completed.
Sponsor:
Collaborator:
Mars, Inc.
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01180127
First received: May 21, 2010
Last updated: August 14, 2014
Last verified: August 2014

May 21, 2010
August 14, 2014
December 2009
October 2013   (final data collection date for primary outcome measure)
CBV (cerebral blood volume) in the dentate gyrus [ Time Frame: Up to 12 weeks after exercise/dietary intervention exposure ] [ Designated as safety issue: No ]
CBV will be measured at randomization, i.e., before exposure to the intervention, and then again after completion of the 12-week intervention
CBV in the dentate gyrus [ Time Frame: change from before to after 12 weeks of the exercise/dietary intervention exposure ] [ Designated as safety issue: No ]
CBV will be measured at randomization, i.e., before exposure to the intervention, and then again after completion of the 12-week intervention
Complete list of historical versions of study NCT01180127 on ClinicalTrials.gov Archive Site
neurocognitive function [ Time Frame: Up to 12 weeks after exercise/dietary intervention exposure ] [ Designated as safety issue: No ]
measured at randomization, i.e., before exposure to the intervention, and then again after completion of the 12-week intervention
neurocognitive function [ Time Frame: change from before to after 12 weeks of the exercise/dietary intervention exposure ] [ Designated as safety issue: No ]
measured at randomization, i.e., before exposure to the intervention, and then again after completion of the 12-week intervention
Not Provided
Not Provided
 
Mars Flavonol Exercise and Cognitive Function Study
Study of the Impact of a Flavonol Containing Food Product and Exercise on Cognitive Function and Brain Structure

This is a randomized controlled trial to test the impact of a flavonol containing food product and aerobic exercise on cognitive function and brain structure.

I. Background and Significance A. The epidemiology of cognitive aging. Encompassing multiple cognitive domains, higher order thinking includes memory, language, abstract reasoning, and visuospatial ability. A range of studies have established that memory is a cognitive domain differentially targeted by the normal aging process. With an increase in lifespan and a decrease in co-morbid diseases, aging individuals expect to lead cognitively-challenging lives. Even mild forgetfulness, therefore, is no longer considered 'benign'. Indeed, with the exponential growth of the aging population, and since memory decline will occur in all of us as we age, age-related memory decline has emerged as a major societal problem.

B. The anatomy of cognitive aging. A range of studies in humans, non-human primates and rodents have established that the hippocampal formation, a brain circuit vital for memory, is targeted by the aging process. Age-related hippocampal dysfunction is therefore a major contributor to age-related memory decline.

The hippocampal formation is organized as a circuit, made up of separate but interconnected regions, including the entorhinal cortex, the dentate gyrus, the CA subfields, and the subiculum. Because of hippocampal circuit properties, dysfunction in one subregion will affect the function of neighboring subregions and the hippocampal circuit as a whole. Thus, when confronted with any process that causes the hippocampal circuit to malfunction, pinpointing the subregion that is most effected becomes an important goal.

In the case of age-related memory decline, a range of studies in humans, non-human primates, and rodents, have suggested that normal aging causes hippocampal dysfunction by differentially targeting the dentate gyrus.

C. Imaging cognitive aging. The anatomical organization of the hippocampal circuit and the differential vulnerability of the dentate gyrus to cognitive aging imposes specific requirements on brain imaging techniques. Specifically, an imaging technique must be able to assess the functional integrity of the multiple hippocampal subregions, in particular the dentate gyrus. With this in mind, our lab has been dedicated to optimizing a functional brain imaging approach applicable to both the human and rodent hippocampal formation. We have recently achieved this goal, and have been applying our cross-species imaging capabilities to investigate a range of process that affect hippocampal function.

D. Flavanols, exercise, and cognitive aging. Previous studies have established that physical exercise improved hippocampal function. We have recently exploited our cross-species imaging techniques to show, that within the hippocampal circuit, exercise has a selective effect on dentate gyrus function, in humans and in mice. Independently, a recent study has shown that the flavanol epichatechin improves hippocampal function, and importantly, within the hippocampal circuit, epichatechin was found to differentially target the dentate gyrus. Moreover, this study showed that epichatechin coupled with exercise had its greatest effect on dentate gyrus function.

E. Summary. Starting at around 30 years of age, all of us will begin experiencing the insidious cognitive slide of age-related memory decline. With the expansion of aging, age-related memory decline is swelling to epidemic proportions, and ameliorating age-related memory decline has emerged as major societal goal.

This proposal is designed to test the following hypothesis: That flavanols with or without physical exercise will ameliorate age-related memory decline. This hypothesis is informed by two sets of interleaving findings: First, a range of studies have pinpointed dysfunction in the dentate gyrus as a specific brain region contributing to age-related memory decline; and second, flavanol consumption with or without physical exercise enhances memory performance by improving dentate gyrus function.

In order to experimentally test this hypothesis an imaging technique is required that can assess the functional integrity of the dentate gyrus, techniques that are now available. Importantly, these imaging techniques have been developed so that can they can be applied not only to humans but also to animal models, generating the same 'imaging readout'. Cross-species imaging is particularly important for translational studies.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Basic Science
Cognitive Function
  • Dietary Supplement: Flavonol containing food product
    12 weeks, 2X/day, 20g serving
    Other Names:
    • Aerobic training
    • Placebo food additive
    • Wait list control
  • Behavioral: Aerobic training
    4X/week, 1 hour/session at 75% maximum HR
    Other Names:
    • Flavonol containing food products
    • Placebo food additive
    • Wait list control
  • Dietary Supplement: Placebo food additive
    20 g serving, 2X/day, food additive lacking flavonol
    Other Names:
    • Flavonol containing food product
    • Aerobic training
    • Wait list control
  • Behavioral: Wait list control
    12 week wait list control condition during which participant abstain from aerobic exercise
    Other Names:
    • Flavonol containing food product
    • Aerobic training
    • Placebo food additive
  • Active Comparator: exercise, dietary intervention
    aerobic training and flavonol containing food product
    Interventions:
    • Dietary Supplement: Flavonol containing food product
    • Behavioral: Aerobic training
  • Active Comparator: no exercise, dietary intervention
    wait list control plus flavonol containing food product for 12 weeks
    Interventions:
    • Dietary Supplement: Flavonol containing food product
    • Behavioral: Wait list control
  • Active Comparator: exercise, food additive lacking flavonol
    aerobic training plus food additive without flavonol
    Interventions:
    • Behavioral: Aerobic training
    • Dietary Supplement: Placebo food additive
  • Placebo Comparator: wait list control food additive without flavonol
    12 weeks of wait list control status plus food additive without the flavonol containing food product
    Interventions:
    • Dietary Supplement: Placebo food additive
    • Behavioral: Wait list control
Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5638-43. Epub 2007 Mar 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
41
October 2013
October 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age 50-75
  2. English-speaking
  3. Ambulatory
  4. BMI < 32
  5. Post-menopausal (women only), no estrogen replacement therapy
  6. VO2max < 36 and 33 ml/kg/min for men age 50-59 and 60-69 respectively; < 29 and 27 ml/kg/min for women age 50-59 and 60-75 respectively.
  7. Baecke Physical Activity Sports Score ≤ 2
  8. Medical clearance to participate in the study (normal serum electrolyte, BUN, creatinine levels, normal blood pressure and resting cardiogram)

Exclusion Criteria:

  1. Use of psychotropic medications
  2. Current psychiatric disorder
  3. Any condition for which aerobic training is counter-indicated
  4. Habitual consumers of dietary or herbal supplements, including Gingko, flavonoid, and dietary herbal or plant extracts
  5. Lactose Intolerance
  6. Individuals who report directly to any of the study investigators
  7. Diabetes

Exclusion Criteria (MRI-related)

  1. Cardiac Pacemaker
  2. Internal Pump
  3. Insulin Pump
  4. Tattoo eyeliner
  5. Wire Sutures
  6. Internal Metal Objects
  7. Metal Slivers in Eye
  8. Prosthesis
  9. Hearing Aid Implants
  10. Neurostimulator
  11. Metal Fragments
  12. Brain Aneurysm Clips
  13. Vascular Clips
  14. Breast Expander
  15. Vena Cava Filter
  16. Heart Valve
  17. Metal Stents
  18. Asthma
  19. Hay-Fever
  20. Sickle Cell Disease
  21. Kidney Disease
  22. Pregnant
Both
50 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01180127
5804
No
New York State Psychiatric Institute
New York State Psychiatric Institute
Mars, Inc.
Principal Investigator: Scott A Small, MD Columbia University
New York State Psychiatric Institute
August 2014

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