Clinical trial NCT03723694: Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders
Official title: Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Memory Loss
Inflammation
Keywords: Flavanol
Cocoapro
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-10-29
Enrollment: 259
Sex: ALL
Minimum age (years): 50
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: HMGB1
timeFrame: 12 weeks
Secondary outcomes:
measure: NFkB
timeFrame: 12 weeks
measure: TNFa
timeFrame: 12 weeks
Other outcomes:
measure: ModBent
timeFrame: 12 weeks
measure: ModRey
timeFrame: 12 weeks
measure: multiple cognitive domains
timeFrame: 12 weeks
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Richard P. Sloan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.