Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders

The purpose of this study is to test the effect of a cocoa-derived dietary flavanol on brain structures and cognitive outcomes in a 12-week randomized controlled trial of 146 healthy participants, age 50-69, who will receive this cocoa derivative or a placebo. Th investigators will also examine the role of inflammation in this relationship.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammation; Memory Loss
• Intervention / Treatment: Dietary supplement: 650 mg of Cocoapro flavanols; Dietary supplement: 0 mg of Cocoapro flavanols

Detailed Description

Within 25 years, the US population aged 65 and over will double in size to 80 million bringing, with it an epidemic of aging-related cognitive decline, from normal cognitive aging to neurodegenerative disorders including Alzheimer's Disease. These conditions impair quality of life and functional status, impose an enormous burden on individuals, their families, the healthcare system, and require elucidation of mechanisms and development of new treatments to prevent or at least slow their progression. The use of plant-based food and drink for health purposes has a long and well-documented history. Cocoa beans contain a substance that has multiple beneficial health effects. In this study, the investigators will test the effect of this substance on brain structures and cognitive outcomes in a 12-week randomized controlled trial of 146 healthy participants, age 50-69, who will receive this cocoa derivative or a placebo. The investigators also will examine the role of inflammation in this relationship. Such a trial has potential for significant clinical impact.

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 screening or management of the subject).
2. Healthy Male or Female subjects. (Females must be post-menopausal)
3. Age between 50 and 69 years, both inclusive.
4. Body mass index between 18.0 and 35 kg/m², both inclusive.

Exclusion Criteria:

1. Currently undergoing medical treatment, including prescription drugs/medication.
2. Clinically significant abnormal hematology, biochemistry, urinalysis, or coagulation screening tests, as judged by the Investigator.
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.
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. Heart Diseases.
6. Hepatitis B or C positive status.
7. HIV positive status.
8. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
9. 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.
10. Adherence to a vegan or vegetarian diet or to specialty/uncommon diets.
11. Food Allergies to tree nuts, soy, cocoa and cocoa-containing products.
12. People who choose to avoid caffeine intake.
13. Current or history of alcoholism or drug/chemical abuse as per Investigator's judgment.
14. Hormone Replacement Therapy; Currently pregnant; Pregnant or Interview\ lactating within past 6 months; Hormonal birth control (pill).
15. Smoking.
16. Unwilling to have blood drawn or anxiety/nausea during a blood draw.
17. Uncomfortable completing memory and attention tasks in the English language
18. Montreal Cognitive Assessment (MoCA) score less than 26.
19. Inability to swallow study capsules Interview (at Consent)
20. 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).

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. Asthmatic symptoms within the past 3 years
19. Sickle Cell Disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 650 mg of Cocoapro flavanols; Daily, each subject will consume either two cocoa flavanol-containing capsules twice a day with a meal.	Dietary supplement: 650 mg of Cocoapro flavanols; 12-week period during which participant will be asked to consume two cocoa-flavanol-containing capsules(650mg) twice a day with meals.
Placebo Comparator: 0mg Cocoapro flavanols; Daily, each subject will consume either ttwo placebo-containing capsules twice a day with a meal.	Dietary supplement: 0 mg of Cocoapro flavanols; 12-week period during which participant will be asked to consume two cocoa-flavanol-containing capsules(0mg) twice a day with meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HMGB1	circulating levels of the inflammatory marker HMGB1	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NFkB	TLR4-dependent NFkB	12 weeks
TNFa	TLR4-dependent TNFa	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ModBent	modified Benton Recognition Task	12 weeks
ModRey	Modified Rey Auditory Verbal Learning Test	12 weeks
multiple cognitive domains	NIH Toolbox Cognition Battery, which includes adaptive computerized tests of executive function, attention, episodic memory, language, processing speed, and working memory	12 weeks

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Richard P. Sloan, PhD, Columbia University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: October 24, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Flavanol; Cocoapro
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Inflammation; Memory Disorders; Neuroinflammatory Diseases
• Other Study ID Numbers: 7665; 5R01AG058417 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No