Dietary Flavanols and Dentate Gyrus Function

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02312310
• Collaborator: Mars, Inc. (Industry)
• Enrollment: 211
• Location: 1
• Arms: 4
• Actual Duration (Months): 52
• Patients Per Site Per Month: 4.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Memory Loss	Dietary Supplement: Cocoa Flavanol	N/A

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 211 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Dietary Cocoa Flavanols and Age-Related Memory Decline
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Nov 1, 2018
• Actual Study Completion Date: Apr 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: F 0 mg daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	Dietary Supplement: Cocoa Flavanol; 12 weeks administration of cocoa flavanol
Active Comparator: 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	Dietary Supplement: Cocoa Flavanol; 12 weeks administration of cocoa flavanol
Active Comparator: F 510 mg daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks	Dietary Supplement: Cocoa Flavanol; 12 weeks administration of cocoa flavanol
Active Comparator: F 770 mg daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks	Dietary Supplement: Cocoa Flavanol; 12 weeks administration of cocoa flavanol

Outcome Measures

Primary Outcome Measures

1. Modified Benton Recognition Task (ModBent) [baseline and 12 weeks]

   The ModBent task is divided into two parts. During the matching trials (top), participants were shown a complex stimulus for 10 s. Following a 1-s inter-trial interval, they were required to select, via a key press, which of two stimuli matched the one they had just studied, as quickly and as accurately as possible. Following 41 matching trials, participants were shown a series of 82 stimuli (bottom), 41 of which appeared on the initial study set during the matching trials and 41 of which were foils. They were required to indicate, as quickly as possible, whether each stimulus appeared earlier (yes response) or was new (no response). The primary variable of the ModBent task is the mean RT for correct rejections of foils during the recognition trials

Secondary Outcome Measures

1. Dentate Gyrus Cerebral Blood Volume [baseline and 12 weeks]

   measured in functional MRI. we generated high-resolution CBV brain maps using gadolinium-enhanced T1-weighted scans acquired perpendicular to the hippocampal long-axis, with sub-millimeter in-plane resolution of 0.68 × 0.68 mm and slice thickness of 3 mm. To perform group-wise voxel-based analyses on the whole hippocampal circuit, we first isolated hippocampal subfields using FreeSurfer segmentations and thresholded posterior probabilities to generate a composite mask of the bilateral hippocampal formation. These masked T1-weighted images were then used to generate a group-wise template to which individual images were co-registered using a diffeomorphic technique that maximizes cross-correlation among images.

2. Modified Benton Recognition Task (ModBent) [20 weeks]

   The ModBent task is divided into two parts. During the matching trials (top), participants were shown a complex stimulus for 10 s. Following a 1-s inter-trial interval, they were required to select, via a key press, which of two stimuli matched the one they had just studied, as quickly and as accurately as possible. Following 41 matching trials, participants were shown a series of 82 stimuli (bottom), 41 of which appeared on the initial study set during the matching trials and 41 of which were foils. They were required to indicate, as quickly as possible, whether each stimulus appeared earlier (yes response) or was new (no response). The primary variable of the ModBent task is the mean RT for correct rejections of foils during the recognition trials

3. Modified Rey Auditory Verbal Learning Test [Baseline and 12 Weeks]

   In learning Trials 1 to 3 the participant is read 20 unique, semantically/phonemically unrelated words (List A) and is to free recall those words after each trial. Next the participant is read a list of 20 unique words (List B) and is to recall as many as possible. This trial is followed by a short delay free recall trial: the participant is to recall as many words as possible from List A. After a 1.5-hour, the participant is asked to long delay free recall words from List A and then from List B. This is followed by a 66-item forced recognition trial: the participant is read a list of 66 words and asked to distinguish List A words from semantic and phonemic distractors, including words from List B. Finally, a source memory trial is administered: the examiner serially reads words from List A and B. The participant is to specify from which list each word came.Higher score indicates better performance. score ranges from 0 to 60.

4. NIH Toolbox Cognition Battery (NIHTB-CB): The List Sorting Test [Baseline and 12 Weeks]

   Participants are presented with a series of stimuli, each of which is both visually and auditorily presented by computer. A picture of each stimulus is displayed on the computer monitor for 2 seconds while the name of the stimulus is simultaneously being read via a computerized voice; stimuli are presented one after another. The participant must remember each stimulus in a series, mentally reorder them from smallest to largest, and recite the names of the stimuli in this order. List Sorting scores are based upon Total Score. Higher score indicated better performance.Score ranges from 0-100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

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

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

3. 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

1. Currently taking SSRI (selective serotonin reuptake inhibitor) medications for any reason. Interview

2. Heart Diseases. Medical History Interview

3. Hepatitis B or C positive status. Medical History Interview

4. HIV positive status. Medical History Interview

5. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction. Medical History Interview

6. 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

7. Adherence to a vegan or vegetarian diet or to specialty/uncommon diets. Interview

8. Food Allergies to tree nuts, soy, cocoa and cocoa-containing products. Interview

9. People who choose to avoid caffeine intake. Interview

10. Current or history of alcoholism or drug/chemical abuse as per Investigator's judgment. Medical History Interview

11. Hormone Replacement Therapy; Currently pregnant; Pregnant or lactating within past 6 mos; Hormonal birth control (pill). Interview

12. Smoking. Interview

13. Unwilling to have blood drawn or anxiety/nausea during a blood draw. Interview.

14. Uncomfortable completing memory and attention tasks in the English language. Interview

15. MoCA (Montreal Cognitive Assessment) score less than 26. Montreal Cognitive Assessment

16. Inability to swallow study capsules. Interview (at consent).

17. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• Mars, Inc.

Investigators

• Principal Investigator: Scott A Small, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Dec 17, 2019
• Statistical Analysis Plan - Oct 23, 2019

More Information

Publications

• 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.
• 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.
• 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.

• Responsible Party: Richard Sloan, Research Scientist / Professor of Behavioral Medicine (in Psychiatry), New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT02312310
• Other Study ID Numbers: 7034
• First Posted: Dec 9, 2014
• Last Update Posted: Jun 11, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Memory Disorders

Study Results

Participant Flow

Recruitment Details	first consent; 1/13/2016 Final data collection session: 11/21/2018 All data collected at Columbia University Medical Center
Pre-assignment Detail	consent: exclusions: 5 BMI too high; 66 MOCA too low; 4 elevated blood pressure; 16 other; 17 lost to follow-up two week run-in period: exclusions: 24 failed, 17 withdrew or lost to follow-up baseline assessments: exclusions: 1 lost to follow-up

Arm/Group Title	0 mg Cocoa Flavanol	260 mg Cocoa Flavanol	510 mg Cocoa Flavanol	770 mg Cocoa Flavanol
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;
Period Title: Overall Study
STARTED	53	53	53	52
COMPLETED	51	51	50	52
NOT COMPLETED	2	2	3	0

Baseline Characteristics

Arm/Group Title	0 mg	260 mg	510 mg	770 mg	Total
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;	Total of all reporting groups
Overall Participants	53	53	53	52	211
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.47 (6.78)	60.81 (6.71)	61 (6.15)	61.23 (6.37)	61.13 (6.47)
Sex: Female, Male (Count of Participants)
Female	31 58.5%	30 56.6%	30 56.6%	29 55.8%	120 56.9%
Male	22 41.5%	23 43.4%	23 43.4%	23 44.2%	91 43.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 7.5%	4 7.5%	8 15.1%	4 7.7%	20 9.5%
Not Hispanic or Latino	49 92.5%	49 92.5%	45 84.9%	48 92.3%	191 90.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	4 7.5%	2 3.8%	4 7.5%	3 5.8%	13 6.2%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.9%	0 0%	0 0%	1 0.5%
Black or African American	7 13.2%	7 13.2%	8 15.1%	8 15.4%	30 14.2%
White	41 77.4%	40 75.5%	38 71.7%	41 78.8%	160 75.8%
More than one race	1 1.9%	3 5.7%	3 5.7%	0 0%	7 3.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	53 100%	53 100%	53 100%	52 100%	211 100%
alternative Healthy Eating Index (aHEI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	65.09 (11.44)	68.78 (10.82)	64.83 (14.3)	66.74 (10.84)	66.36 (12)
5-(3',4'-dihydroxyphenyl)-γ-valerolactone (gVLM) (nM) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nM]	19.7 (24.23)	20.98 (34.28)	44.32 (72.4)	36.59 (72.06)	30.44 (55.84)

Outcome Measures

1. Primary Outcome

Title	Modified Benton Recognition Task (ModBent)
Description	The ModBent task is divided into two parts. During the matching trials (top), participants were shown a complex stimulus for 10 s. Following a 1-s inter-trial interval, they were required to select, via a key press, which of two stimuli matched the one they had just studied, as quickly and as accurately as possible. Following 41 matching trials, participants were shown a series of 82 stimuli (bottom), 41 of which appeared on the initial study set during the matching trials and 41 of which were foils. They were required to indicate, as quickly as possible, whether each stimulus appeared earlier (yes response) or was new (no response). The primary variable of the ModBent task is the mean RT for correct rejections of foils during the recognition trials
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0 mg Cocoa Flavanol	260 mg Cocoa Flavanol	510 mg Cocoa Flavanol	770 mg Cocoa Flavanol
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;
Measure Participants	51	51	50	52
Baseline	2807.98 (1733.36)	2579.94 (1026.18)	2603.65 (999.31)	2732.79 (1367.96)
12 Weeks	2671.50 (1431.17)	2489.84 (1135.40)	2381.68 (929.14)	2653.01 (1289.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0 mg Cocoa Flavanol, 260 mg Cocoa Flavanol, 510 mg Cocoa Flavanol, 770 mg Cocoa Flavanol
	Comments
	Type of Statistical Test	Superiority
	Comments	Test of trend across doses.
Statistical Test of Hypothesis	p-Value	.393
	Comments
	Method	Mixed Models Analysis
	Comments	Change in outcome from baseline to 12 weeks tested using mixed effects models controlling for baseline measures, treatment, sex, age, and education.
Other Statistical Analysis		The flavanol effect on the change in each outcome from baseline to 12 weeks was tested using linear mixed effects models controlling for the respective baseline measures, four categories of treatment, sex, age, and education. Regression adjusted mean within-group tests of change were estimated and tested for statistical significance from the model. The primary test used for assessing the treatment effect was the linear trend contrast from the model across: placebo, low, medium and high dose. The model for cognitive measures incorporated additional outcome measurement times at 4 weeks and 20 weeks and included categorical time (4, 12, 20 weeks) as a predictor as well as a treatment (4 category) by time interaction, and a random intercept to control for repeated measures within individuals (results for 4 and 20 weeks not presented).

2. Secondary Outcome

Title	Dentate Gyrus Cerebral Blood Volume
Description	measured in functional MRI. we generated high-resolution CBV brain maps using gadolinium-enhanced T1-weighted scans acquired perpendicular to the hippocampal long-axis, with sub-millimeter in-plane resolution of 0.68 × 0.68 mm and slice thickness of 3 mm. To perform group-wise voxel-based analyses on the whole hippocampal circuit, we first isolated hippocampal subfields using FreeSurfer segmentations and thresholded posterior probabilities to generate a composite mask of the bilateral hippocampal formation. These masked T1-weighted images were then used to generate a group-wise template to which individual images were co-registered using a diffeomorphic technique that maximizes cross-correlation among images.
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0 mg Cocoa Flavanol	260 mg Cocoa Flavanol	510 mg Cocoa Flavanol	770 mg Cocoa Flavanol
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;
Measure Participants	14	10	13	12
Baseline	2.44 (.81)	2.17 (.69)	2.11 (0.47)	1.85 (0.67)
12 Weeks	2.25 (.57)	2.11 (.52)	2.01 (.71)	2.23 (.59)

3. Secondary Outcome

Title	Modified Benton Recognition Task (ModBent)
Description	The ModBent task is divided into two parts. During the matching trials (top), participants were shown a complex stimulus for 10 s. Following a 1-s inter-trial interval, they were required to select, via a key press, which of two stimuli matched the one they had just studied, as quickly and as accurately as possible. Following 41 matching trials, participants were shown a series of 82 stimuli (bottom), 41 of which appeared on the initial study set during the matching trials and 41 of which were foils. They were required to indicate, as quickly as possible, whether each stimulus appeared earlier (yes response) or was new (no response). The primary variable of the ModBent task is the mean RT for correct rejections of foils during the recognition trials
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0 mg Cocoa Flavanol	260 mg Cocoa Flavanol	510 mg Cocoa Flavanol	770 mg Cocoa Flavanol
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;
Measure Participants	50	49	50	51
Mean (Standard Deviation) [ms]	2542.76 (1278.87)	2475.35 (1512.88)	2373.78 (934.84)	2550.18 (1165.92)

4. Secondary Outcome

Title	Modified Rey Auditory Verbal Learning Test
Description	In learning Trials 1 to 3 the participant is read 20 unique, semantically/phonemically unrelated words (List A) and is to free recall those words after each trial. Next the participant is read a list of 20 unique words (List B) and is to recall as many as possible. This trial is followed by a short delay free recall trial: the participant is to recall as many words as possible from List A. After a 1.5-hour, the participant is asked to long delay free recall words from List A and then from List B. This is followed by a 66-item forced recognition trial: the participant is read a list of 66 words and asked to distinguish List A words from semantic and phonemic distractors, including words from List B. Finally, a source memory trial is administered: the examiner serially reads words from List A and B. The participant is to specify from which list each word came.Higher score indicates better performance. score ranges from 0 to 60.
Time Frame	Baseline and 12 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0 mg	260 mg	510 mg	770 mg
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;
Measure Participants	51	51	50	52
Baseline	38.91 (8.45)	37.25 (8.19)	39.75 (7.38)	39.96 (9.62)
12 Weeks	39.49 (9.70)	38.69 (9.30)	41.10 (8.50)	41.92 (8.48)

5. Secondary Outcome

Title	NIH Toolbox Cognition Battery (NIHTB-CB): The List Sorting Test
Description	Participants are presented with a series of stimuli, each of which is both visually and auditorily presented by computer. A picture of each stimulus is displayed on the computer monitor for 2 seconds while the name of the stimulus is simultaneously being read via a computerized voice; stimuli are presented one after another. The participant must remember each stimulus in a series, mentally reorder them from smallest to largest, and recite the names of the stimuli in this order. List Sorting scores are based upon Total Score. Higher score indicated better performance.Score ranges from 0-100.
Time Frame	Baseline and 12 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0 mg	260 mg	510 mg	770 mg
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks	daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;	daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;
Measure Participants	51	51	50	52
Baseline	52.89 (8.85)	56.81 (8.91)	54.60 (9.15)	55.18 (8.65)
12 Weeks	53.34 (7.44)	56.10 (8.47)	54.86 (8.56)	53.46 (9.23)

Adverse Events

Time Frame	adverse events were monitored each week throughout the study and for the MRI substudy, at each of the two MRI sessions
Arm/Group Title	0 mg Cocoa Flavanol		260 mg Cocoa Flavanol		510 mg Cocoa Flavanol		770 mg Cocoa Flavanol
Arm/Group Description	daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks		daily consumption of capsules containing 260 mg cocoa flavanol for 12 weeks;		daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks;		daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks;
All Cause Mortality
	0 mg Cocoa Flavanol		260 mg Cocoa Flavanol		510 mg Cocoa Flavanol		770 mg Cocoa Flavanol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/53 (0%)		0/53 (0%)		0/52 (0%)
Serious Adverse Events
	0 mg Cocoa Flavanol		260 mg Cocoa Flavanol		510 mg Cocoa Flavanol		770 mg Cocoa Flavanol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/53 (0%)		0/53 (0%)		0/52 (0%)
Other (Not Including Serious) Adverse Events
	0 mg Cocoa Flavanol		260 mg Cocoa Flavanol		510 mg Cocoa Flavanol		770 mg Cocoa Flavanol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/53 (0%)		0/53 (0%)		0/52 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.