Dietary Flavanols and Dentate Gyrus Function

NCT ID: NCT02312310

Last Updated: 2020-06-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

211 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2020-04-30

Brief Summary

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to assess the effect of differing amounts of a cocoa-derived dietary flavanol (epicatechin ) on dentate gyrus function and corresponding cognitive function

Detailed Description

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In this double blinded trial, the participants, age 50-75 years, will be randomized to receive 0, 260, 510, or 770 mg daily\* for 12 weeks and will be tested before and after the intervention. Cognitive testing will be conducted prior to randomization, and at weeks 4, 12, and 20 of the study.

In an optional substudy, fMRI (functional magnetic resonance imaging) with gadolinium contrast will be conducted to measure dentate gyrus function before randomization and then after completion of the 12-week intervention portion of the trial.

\*see note in Record Log regarding the change in the method of assessment of cocoa flavanol content of the capsules

Conditions

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Memory Loss

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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F 0 mg

daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks

Group Type PLACEBO_COMPARATOR

Cocoa Flavanol

Intervention Type DIETARY_SUPPLEMENT

12 weeks administration of cocoa flavanol

F 260 mg

daily consumption of capsules containing 260 mg\* cocoa flavanol for 12 weeks

\*see note in Record Log regarding the change in the method of assessment of cocoa flavanol content of the capsules

Group Type ACTIVE_COMPARATOR

Cocoa Flavanol

Intervention Type DIETARY_SUPPLEMENT

12 weeks administration of cocoa flavanol

F 510 mg

daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks

Group Type ACTIVE_COMPARATOR

Cocoa Flavanol

Intervention Type DIETARY_SUPPLEMENT

12 weeks administration of cocoa flavanol

F 770 mg

daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks

Group Type ACTIVE_COMPARATOR

Cocoa Flavanol

Intervention Type DIETARY_SUPPLEMENT

12 weeks administration of cocoa flavanol

Interventions

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Cocoa Flavanol

12 weeks administration of cocoa flavanol

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* 1\. Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject). Telephone Screen

2\. Healthy Male or Female subjects. (Females must be post-menopausal) Telephone Screen

3\. Age between 50 and 75 years, both inclusive. Telephone Screen

4\. Body mass index between 18.0 and 35 kg/m², both inclusive. Telephone Screen

Exclusion Criteria

1. Currently undergoing medical treatment, including prescription drugs/medication. Medical History Interview
2. Clinically significant abnormal hematology, biochemistry, urinalysis, or coagulation screening tests, as judged by the Investigator. Medical History Interview
3. History or presence of cancer (except basal cell skin cancer or squamous cell skin cancer), or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (with the exception euthyroid struma), haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders as judged by the Investigator. Medical History Interview
4. Seated blood pressure at screening (after resting for 5 min in seated position) outside the range of 90-140 mmHg for systolic or 50-90 mmHg for diastolic (excluding white-coat hypertension; therefore, if a repeated measurement shows values within the range, the subject can be included in the trial) and/or resting supine heart rate outside the range 50-90 beats per minute. Measurement taken at consent before eligibility is determined
5. Current Depression or Anxiety Symptoms using PHQ-8 (eight-item Patient Health Questionnaire depression scale) and GAD-7 (Generalized Anxiety Disorder 7-item scale). PHQ-8 score \>= 10 and/or GAD-7 score \>= 10 are excluded.

(Past history of disorders not exclusionary). Interview
6. Currently taking SSRI (selective serotonin reuptake inhibitor) medications for any reason. Interview
7. Heart Diseases. Medical History Interview
8. Hepatitis B or C positive status. Medical History Interview
9. HIV positive status. Medical History Interview
10. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction. Medical History Interview
11. Use of non-prescription medication, herbal products or nutritional supplements during the study, and within the last 4 weeks before the start of the study (screening), as judged by the Investigator; occasional use of aspirin, ibuprofen, acetaminophen is permitted. Interview
12. Adherence to a vegan or vegetarian diet or to specialty/uncommon diets. Interview
13. Food Allergies to tree nuts, soy, cocoa and cocoa-containing products. Interview
14. People who choose to avoid caffeine intake. Interview
15. Current or history of alcoholism or drug/chemical abuse as per Investigator's judgment. Medical History Interview
16. Hormone Replacement Therapy; Currently pregnant; Pregnant or lactating within past 6 mos; Hormonal birth control (pill). Interview
17. Smoking. Interview
18. Unwilling to have blood drawn or anxiety/nausea during a blood draw. Interview.
19. Uncomfortable completing memory and attention tasks in the English language. Interview
20. MoCA (Montreal Cognitive Assessment) score less than 26. Montreal Cognitive Assessment
21. Inability to swallow study capsules. Interview (at consent).
22. Did not complete the two weeks Run-In Period (Participants who missed more than 2 intake occasions out of 14 days (28 occasions total) or if there are \> 8 capsules left in the bottle after the two weeks will be excluded). Run-In Period.

MRI RELATED

1. Cardiac Pacemaker Interview
2. Internal Pump Interview
3. Insulin Pump Interview
4. Tattoo eyeliner Interview
5. Wire sutures Interview
6. Internal Metal Objects Interview
7. Metal Slivers in Eye Interview
8. Prosthesis Interview
9. Hearing Aid Implants Interview
10. Neurostimulator Interview
11. Metal Fragments Interview
12. Brain Aneurysm Clips Interview
13. Vascular Clips Interview
14. Breast Expander Interview
15. Vena Cava Filter Interview
16. Heart Valve Interview
17. Metal Stents Interview
18. Asthma Interview
19. Hay-Fever Interview
20. Sickle Cell Disease Interview
21. Kidney Disease Interview
22. Pregnant Interview
23. Claustrophobic Interview
24. Wheelchair bound Interview
25. Machinist or ever worked with heavy metals Interview
26. Contraindication to Gadolinium, including prior adverse reaction to gadolinium, past or current history of severe breathing difficulty that has been treated by a physician (e.g. asthma, COPD (Chronic obstructive pulmonary disease), etc) and sickle cell disease. History of renal impairment or estimated glomerular filtration rate \<30 L/min.1.732m2 is also exclusionary Interview; Glomerular filtration rate assessed with creatinine via StatSensor monitor
27. Had more than one previous MRI scans with Gadolinium Interview
Minimum Eligible Age

50 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Mars, Inc.

INDUSTRY

Sponsor Role collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role lead

Responsible Party

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Richard Sloan

Research Scientist / Professor of Behavioral Medicine (in Psychiatry)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Scott A Small, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Columbia University Medical Center

New York, New York, United States

Site Status

Countries

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United States

References

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Brickman AM, Khan UA, Provenzano FA, Yeung LK, Suzuki W, Schroeter H, Wall M, Sloan RP, Small SA. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nat Neurosci. 2014 Dec;17(12):1798-803. doi: 10.1038/nn.3850. Epub 2014 Oct 26.

Reference Type BACKGROUND
PMID: 25344629 (View on PubMed)

Bussy U , May BR , Olanrewaju Y , Hewitt G , Anderson N , Crozier A , Ottaviani JI , Kwik-Uribe C . Reliable, accessible and transferable method for the quantification of flavanols and procyanidins in foodstuffs and dietary supplements. Food Funct. 2020 Jan 29;11(1):131-138. doi: 10.1039/c9fo02762a.

Reference Type BACKGROUND
PMID: 31932823 (View on PubMed)

Ottaviani JI, Fong R, Kimball J, Ensunsa JL, Britten A, Lucarelli D, Luben R, Grace PB, Mawson DH, Tym A, Wierzbicki A, Khaw KT, Schroeter H, Kuhnle GGC. Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies. Sci Rep. 2018 Jun 29;8(1):9859. doi: 10.1038/s41598-018-28333-w.

Reference Type BACKGROUND
PMID: 29959422 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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7034

Identifier Type: -

Identifier Source: org_study_id

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