New York, New York 10032

  • Memory Loss

Purpose:

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


Study summary:

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


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 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


Study is Available At:


Original ID:

7034


NCT ID:

NCT02312310


Secondary ID:


Study Acronym:


Brief Title:

Dietary Flavanols and Dentate Gyrus Function


Official Title:

Dietary Cocoa Flavanols and Age-Related Memory Decline


Overall Status:

Completed


Study Phase:

N/A


Genders:

N/A


Minimum Age:

50 Years


Maximum Age:

75 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

New York State Psychiatric Institute


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

4


Number of Groups:

0


Total Enrollment:

211


Enrollment Type:

Actual


Overall Contact Information

Official Name:Scott A Small, MD
Principal Investigator
Columbia University

Study Dates

Start Date:December 2015
Completion Date:April 2020
Completion Type:Actual
Primary Completion Date:November 2018
Primary Completion Type:Actual
Verification Date:June 2020
Last Changed Date:June 1, 2020
First Received Date:December 5, 2014
First Results Date:February 4, 2020

Study Outcomes

Outcome Type:Primary Outcome
Measure:Modified Benton Recognition Task (ModBent)
Time Frame:baseline and 12 weeks
Safety Issues:False
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 th
Outcome Type:Secondary Outcome
Measure:Dentate Gyrus Cerebral Blood Volume
Time Frame:baseline and 12 weeks
Safety Issues:False
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.
Outcome Type:Secondary Outcome
Measure:Modified Benton Recognition Task (ModBent)
Time Frame:20 weeks
Safety Issues:False
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 th
Outcome Type:Secondary Outcome
Measure:Modified Rey Auditory Verbal Learning Test
Time Frame:Baseline and 12 Weeks
Safety Issues:False
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
Outcome Type:Secondary Outcome
Measure:NIH Toolbox Cognition Battery (NIHTB-CB): The List Sorting Test
Time Frame:Baseline and 12 Weeks
Safety Issues:False
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

Study Interventions

Intervention Type:Dietary Supplement
Name:Cocoa Flavanol
Description:12 weeks administration of cocoa flavanol
Arm Name:F 0 mg

Study Arms

Study Arm Type:Active Comparator
Arm Name:F 770 mg
Description:daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks
Study Arm Type:Active Comparator
Arm Name:F 510 mg
Description:daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks
Study Arm Type:Active Comparator
Arm Name:F 260 mg
Description: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
Study Arm Type:Placebo Comparator
Arm Name:F 0 mg
Description:daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:New York State Psychiatric Institute
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Mars, Inc.

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation: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.
PMID:29959422
Reference Type:Reference
Citation: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.
PMID:31932823
Reference Type:Reference
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.
PMID:25344629

Data Source: ClinicalTrials.gov

Date Processed: August 01, 2021

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