Memory LossNCT02312310
Dietary Flavanols and Dentate Gyrus Function
A study testing Cocoa Flavanol in people with Memory Loss, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
to assess the effect of differing amounts of a cocoa-derived dietary flavanol (epicatechin ) on dentate gyrus function and corresponding cognitive function Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Memory Loss
- What is being tested?
- Cocoa Flavanol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 211 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Apr 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Currently undergoing medical treatment, including prescription drugs/medication. Medical History Interview
- Clinically significant abnormal hematology, biochemistry, urinalysis, or coagulation screening tests, as judged by the Investigator. Medical History Interview
- 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
- 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
- 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
Show all 51Show fewer
- Currently taking SSRI (selective serotonin reuptake inhibitor) medications for any reason. Interview
- Heart Diseases. Medical History Interview
- Hepatitis B or C positive status. Medical History Interview
- HIV positive status. Medical History Interview
- History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction. Medical History Interview
- 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
- Adherence to a vegan or vegetarian diet or to specialty/uncommon diets. Interview
- Food Allergies to tree nuts, soy, cocoa and cocoa-containing products. Interview
- People who choose to avoid caffeine intake. Interview
- Current or history of alcoholism or drug/chemical abuse as per Investigator's judgment. Medical History Interview
- Hormone Replacement Therapy; Currently pregnant; Pregnant or lactating within past 6 mos; Hormonal birth control (pill). Interview
- Smoking. Interview
- Unwilling to have blood drawn or anxiety/nausea during a blood draw. Interview.
- Uncomfortable completing memory and attention tasks in the English language. Interview
- MoCA (Montreal Cognitive Assessment) score less than 26. Montreal Cognitive Assessment
- Inability to swallow study capsules. Interview (at consent).
- 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
- Cardiac Pacemaker Interview
- Internal Pump Interview
- Insulin Pump Interview
- Tattoo eyeliner Interview
- Wire sutures Interview
- Internal Metal Objects Interview
- Metal Slivers in Eye Interview
- Prosthesis Interview
- Hearing Aid Implants Interview
- Neurostimulator Interview
- Metal Fragments Interview
- Brain Aneurysm Clips Interview
- Vascular Clips Interview
- Breast Expander Interview
- Vena Cava Filter Interview
- Heart Valve Interview
- Metal Stents Interview
- Asthma Interview
- Hay-Fever Interview
- Sickle Cell Disease Interview
- Kidney Disease Interview
- Pregnant Interview
- Claustrophobic Interview
- Wheelchair bound Interview
- Machinist or ever worked with heavy metals Interview
- 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
- Had more than one previous MRI scans with Gadolinium Interview
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Dietary Cocoa Flavanols and Age-Related Memory Decline
to assess the effect of differing amounts of a cocoa-derived dietary flavanol (epicatechin ) on dentate gyrus function and corresponding cognitive function
Read the 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
- Conditions
- Memory Loss
- Being tested
- Cocoa Flavanol
- Medical subject headings
- Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cocoa FlavanolDietary supplement
12 weeks administration of cocoa flavanol
| Study group | Role | What they receive |
|---|---|---|
| F 0 mg | Placebo comparator | daily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks Receives: Dietary Supplement: Cocoa Flavanol |
| F 260 mg | Active comparator | 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 Receives: Dietary Supplement: Cocoa Flavanol |
| F 510 mg | Active comparator | daily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks Receives: Dietary Supplement: Cocoa Flavanol |
| F 770 mg | Active comparator | daily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks Receives: Dietary Supplement: Cocoa Flavanol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Benton Recognition Task (ModBent)
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
Measured: baseline and 12 weeks
Secondary outcomes (4)
Dentate Gyrus Cerebral Blood Volume
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.
Measured: baseline and 12 weeks
Modified Benton Recognition Task (ModBent)
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
Measured: 20 weeks
Modified Rey Auditory Verbal Learning Test
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.
Measured: Baseline and 12 Weeks
NIH Toolbox Cognition Battery (NIHTB-CB): The List Sorting Test
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.
Measured: Baseline and 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2014 (estimated)
- Study startDec 2015
- Primary completionNov 2018
- Study completionApr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Memory LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 211 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Mars, Inc.
- Responsible party
- Principal investigator, Richard Sloan, New York State Psychiatric Institute
- Investigators
- Scott A Small, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02312310
- Sponsor's protocol ID
- 7034
- Status last verified
- Jun 2020
- First submitted
- 5 Dec 2014
- Last updated
- 11 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 25344629Bussy 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.
PubMed 31932823Ottaviani 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.
PubMed 29959422
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Cocoa Flavanols and Age-Related Memory Decline
- ClinicalTrials.gov ID
- NCT02312310
- Acronym / sponsor ID
- 7034
- Conditions
- Memory Loss
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 211 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Mars, Inc.
- Study start
- Dec 2015 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Apr 2020 (actual)
- First posted
- 9 Dec 2014 (estimated)
- Results
- Posted 11 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
to assess the effect of differing amounts of a cocoa-derived dietary flavanol (epicatechin ) on dentate gyrus function and corresponding cognitive function
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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| F 0 mg | Placebo comparator | Dietary Supplement: Cocoa Flavanoldaily consumption of capsules containing 0 mg cocoa flavanol for 12 weeks |
| F 260 mg | Active comparator | Dietary Supplement: Cocoa Flavanoldaily 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 |
| F 510 mg | Active comparator | Dietary Supplement: Cocoa Flavanoldaily consumption of capsules containing 510 mg cocoa flavanol for 12 weeks |
| F 770 mg | Active comparator | Dietary Supplement: Cocoa Flavanoldaily consumption of capsules containing 770 mg cocoa flavanol for 12 weeks |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (51 listed)
- Currently undergoing medical treatment, including prescription drugs/medication. Medical History Interview
- Clinically significant abnormal hematology, biochemistry, urinalysis, or coagulation screening tests, as judged by the Investigator. Medical History Interview
- 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
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cocoa Flavanol12 weeks administration of cocoa flavanol | Dietary supplement | F 0 mg, F 260 mg, F 510 mg, F 770 mg |
Primary outcome
Modified Benton Recognition Task (ModBent)
Time frame: 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
4 secondary outcomes
Dentate Gyrus Cerebral Blood Volume
Time frame: baseline and 12 weeks
Modified Benton Recognition Task (ModBent)
Time frame: 20 weeks
Modified Rey Auditory Verbal Learning Test
Time frame: Baseline and 12 Weeks
NIH Toolbox Cognition Battery (NIHTB-CB): The List Sorting Test
Time frame: Baseline and 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25344629Brickman 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.
- Background: PubMed 31932823Bussy 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.
- Background: PubMed 29959422Ottaviani 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott A Small, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cocoa Flavanol in people with Memory Loss, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 51 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Benton Recognition Task (ModBent) (time frame: baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02312310, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.