Mars Flavanol Exercise and Cognitive Function Study

NCT ID: NCT01180127

Last Updated: 2018-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-10-31

Brief Summary

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.

Detailed Description

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.

Conditions

Cognitive Function

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

exercise, dietary intervention

aerobic training and flavanol containing food product for 12 weeks

Group Type: ACTIVE_COMPARATOR

Flavanol containing food product

Intervention Type: DIETARY_SUPPLEMENT

12 weeks, 2X/day, 20g serving

Aerobic training

Intervention Type: BEHAVIORAL

4X/week, 1 hour/session at 75% maximum HR

no exercise, dietary intervention

wait list control plus flavanol containing food product for 12 weeks

Group Type: ACTIVE_COMPARATOR

Flavanol containing food product

Intervention Type: DIETARY_SUPPLEMENT

12 weeks, 2X/day, 20g serving

Wait list control

Intervention Type: BEHAVIORAL

12 week wait list control condition during which participants abstain from aerobic exercise

exercise, food product lacking flavanol

aerobic training plus food product without flavanol for 12 weeks

Group Type: ACTIVE_COMPARATOR

Aerobic training

Intervention Type: BEHAVIORAL

4X/week, 1 hour/session at 75% maximum HR

Food product lacking flavanol

Intervention Type: DIETARY_SUPPLEMENT

20 g serving, 2X/day, food additive lacking flavonol

wait list control food additive without flavanol

wait list control plus food product without flavanol for 12 weeks

Group Type: PLACEBO_COMPARATOR

Food product lacking flavanol

Intervention Type: DIETARY_SUPPLEMENT

20 g serving, 2X/day, food additive lacking flavonol

Wait list control

Intervention Type: BEHAVIORAL

12 week wait list control condition during which participants abstain from aerobic exercise

Interventions

Flavanol containing food product

12 weeks, 2X/day, 20g serving

Intervention Type: DIETARY_SUPPLEMENT

Aerobic training

4X/week, 1 hour/session at 75% maximum HR

Intervention Type: BEHAVIORAL

Food product lacking flavanol

20 g serving, 2X/day, food additive lacking flavonol

Intervention Type: DIETARY_SUPPLEMENT

Wait list control

12 week wait list control condition during which participants abstain from aerobic exercise

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mars, Inc.

INDUSTRY

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Richard Sloan

Research Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott A Small, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

References

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. doi: 10.1073/pnas.0611721104. Epub 2007 Mar 20.

Reference Type: BACKGROUND

PMID: 17374720 (View on PubMed)

Other Identifiers

5804

Identifier Type: -

Identifier Source: org_study_id