DepressionFlavanolNCT02943096
Flavanol Augmentation for Antidepressant Non-Responsive Late Life Depression
A study testing CocoaVia in people with Depression and Major Depressive Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
The goal of this proposal is to conduct the first pilot study of whether consuming flavanol supplements will augment the cognitive and mood benefits of antidepressant medication in older adults with Late LifeDepression (LLD). Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Depression, Major Depressive Disorder
- What is being tested?
- CocoaVia
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to 6 Feb 2018
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged ≥60 years (Method of ascertainment: clinical interview)
- DSM 5 diagnosis of Major Depressive Disorder (Method of ascertainment: SCID, clinical interview)
- Subjective report of memory or thinking problems (Method of ascertainment: clinical interview)
- 24-item Hamilton Rating Scale for Depression ≥16 (Method of ascertainment: HRSD)
- Failure of depressive symptoms to remit following an adequate trial of an antidepressant (defined as at least 8 weeks of treatment, with 4 weeks of at least half PDR maximum dose, of an FDA approved antidepressant) (Method of ascertainment: clinical interview)
- Capable of providing informed consent and complying with the study procedures (Method of ascertainment: clinical interview)
Who cannot join
- Diagnosis of Substance Use Disorder within the past 12 months (excluding Tobacco) (Method of ascertainment: SCID, clinical interview)
- History of psychosis, psychotic disorder, mania, or bipolar disorder (Method of ascertainment: SCID, clinical interview)
- HRSD suicide item > 2 or CGI =7 at baseline (Method of ascertainment: HRSD, CGI)
- Diagnosis of probable or definite dementia (Alzheimer's Disease, Vascular Dementia, Parkinson's disease, etc.) (Method of ascertainment: SCID, clinical interview, MMSE)
- MMSE ≤24 (Method of ascertainment: MMSE)
- Physical or intellectual disability adversely affecting ability to complete assessments (Method of ascertainment: clinical interview)
Show all 11Show fewer
- History of allergy, hypersensitivity, or intolerance to cocoa flavanols (Method of ascertainment: clinical interview)
- Contraindication to MRI scanning or unable to tolerate scanning procedures (Method of ascertainment: clinical interview)
- Allergic or adverse reaction to gadolinium, 2 or more prior scans with gadolinium, or creatinine clearance < 50 (Method of ascertainment: clinical interview, blood draw)
- Daily consumers of dietary or herbal supplements, including Gingko, flavonoid, and dietary herbal or plant extracts (Method of ascertainment: clinical interview)
- Diabetes or acute, severe, or unstable medical or neurologic condition (Method of ascertainment: clinical interview, physical exam, EKG)
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
The goal of this proposal is to conduct the first pilot study of whether consuming flavanol supplements will augment the cognitive and mood benefits of antidepressant medication in older adults with Late LifeDepression (LLD). Flavanols represent a specific group of plant derived nutrients that are found in cocoa beans, grapes, tea, berries and various other fruits and vegetables. The specific flavanols investigated in this study come from cocoa. Currently available treatments for LLD (i.e., antidepressant medication) are limited in efficacy, especially in individuals who also suffer from cognitive impairment. Recent studies performed at Columbia and elsewhere suggest that flavanols may induce beneficial brain changes that support cognitive functioning and elevate mood, but their precise clinical effects in older adults with combined depression and cognitive impairment remain to be evaluated. For this study, the investigators plan to recruit 50 adults aged ≥60 years who have Major Depressive Disorder, meet a minimum depressive symptom threshold despite currently receiving an adequate trial of an antidepressant, and have a significant cognitive complaints without a diagnosis of dementia. Subjects will be randomized to receive 8 weeks of augmentation treatment with flavanol capsules (in addition to continuing their antidepressant) vs. capsules not containing flavanols. Pre- and post-treatment MRI scanning of the brain will be conducted, and comprehensive pre- and post-treatment neuropsychological assessment will be performed. Results from this project will allow the investigators to evaluate a novel therapeutic approach to LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD.
Read the detailed description
The goal of this proposal is to conduct the first pilot study of whether consuming a diet high in flavanols will augment the cognitive and mood benefits of antidepressant medication in older adults with Late Life Depression (LLD). LLD affects 3% of community-dwelling adults over 60 years old, and 15% of older adults living in the community have clinically significant depressive symptoms. Diagnosis with LLD increases an older adult's risk of disability by 67-73% over 6 year follow up, causes twice the functional impairment compared to those without LLD, and is associated with high rates of completed suicide in individuals over 65. Currently available treatments for LLD (i.e., antidepressant medication) are limited in efficacy, leading to high rates of recurrence and frequent development of chronicity. Cognitive impairment, which is commonly associated with LLD, predicts poor acute response to antidepressants, leads to higher relapse rates during the continuation phase of treatment, and is associated with the development of adverse age-related health outcomes, including increased risk of dementia, dependence in activities of daily living (ADL), and driving cessation.
Novel treatments addressing LLD's underlying neurobiology are critically needed, particularly therapies that may also have beneficial effects on the cognitive components of LLD. The most extensively studied brain region to be implicated in both the depressive and cognitive aspects of LLD has been the hippocampus. Decreased hippocampal volumes are found in depressed patients compared to controls, and this finding appears to be particularly pronounced in individuals with recurrent depressive illness. Among the subregions comprising the hippocampus, evidence suggests that it is decreased neurogenesis within the dentate gyrus (DG) specifically that may contribute to the development of depression, and it appears that part of the mechanism of action of antidepressants is to enhance neurogenesis in the DG. As the DG is also a critical contributor to the cognitive functions of the hippocampus, it stands out as a highly significant brain region that may be involved with both the mood and cognitive components of LLD.
- Conditions
- Depression, Major Depressive Disorder
- Being tested
- CocoaVia, Placebo
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CocoaViaDietary supplement
Flavanols represent a specific group of plant derived nutrients that are found in cocoa beans, grapes, tea, berries and various other fruits and vegetables. The specific flavanols investigated in this study come from cocoa.
PlaceboOther
The placebo looks like the other intervention pills, but does not contain any flavanols (it is sometimes called a "sugar pill").
| Study group | Role | What they receive |
|---|---|---|
| Flavanol | Active comparator | Blinded treatment with either CocoaVia 500mg or placebo. Receives: Dietary Supplement: CocoaVia |
| Placebo | Placebo comparator | Blinded treatment with either CocoaVia 500mg or placebo. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Rating Scale of Depression (HRSD)
Scale for depressive symptoms administered by trained rater. The HRSD is the standard measure of depression severity for clinical trials of antidepressants and was chosen as the primary outcome measure over other depression rating scales to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. Although the HRSD list 21 items, the scoring is based on the first 24 items. The minimum score is 0 and the maximum score is 74. The higher the number the worse outcome.
Measured: Week 8
Secondary outcomes (4)
Mnemonic Similarity Task (MST)
First, participants had to complete an encoding task were they were shown 128 items, ½ objects(2 seconds) and ½ scene (3 seconds). Right after, they were given instructions on a video on how to do the test phase. They were instructed to identified the following images as "old", "similar", or "new". They were then shown 192 items: 64 old items, 64 lures (similar), and 64 foil (new) for 2.5 seconds (objects)/3 seconds (scene). The images were intermixed during the test. The Lure Discrimination Index was calculated as the difference between the rate of "similar" responses give to lure items minus "similar" responses given to foil. This corrected for response bias. Correct responses are those that were identified correctly by the participant. A negative response means that the number of answered correctly was less that those answered incorrectly.
Measured: Baseline
Modified-Benton Task (ModBent)
The ModBent assesses pattern separation, a measure of cognitive functioning. The task was created to measure dentate gyrus-dependent cognition. It shows participants patterns for 10 seconds, then presents two patterns afterwards on a different screen. Participants are then asked to determine which of the two patterns is the one they previously studied for 10 seconds. The second component of the task then goes through a series of patterns, one by one - the participant has to then decide whether each pattern was one they previously studied for 10 seconds or not. We analyzed the mean Reaction time for correct rejections.
Measured: Week 8
Modified-Benton Task (ModBent)
The ModBent assesses pattern separation, a measure of cognitive functioning. The task was created to measure dentate gyrus-dependent cognition. It shows participants patterns for 10 seconds, then presents two patterns afterwards on a different screen. Participants are then asked to determine which of the two patterns is the one they previously studied for 10 seconds. The second component of the task then goes through a series of patterns, one by one - the participant has to then decide whether each pattern was one they previously studied for 10 seconds or not. We analyzed the mean Reaction time for correct rejections.
Measured: Baseline
Mnemonic Similarity Task (MST)
First, participants had to complete an encoding task were they were shown 128 items, ½ objects(2 seconds) and ½ scene (3 seconds). Right after, they were given instructions on a video on how to do the test phase. They were instructed to identified the following images as "old", "similar", or "new". They were then shown 192 items: 64 old items, 64 lures (similar), and 64 foil (new) for 2.5 seconds (objects)/3 seconds (scene). The images were intermixed during the test. The Lure Discrimination Index was calculated as the difference between the rate of "similar" responses give to lure items minus "similar" responses given to foil. This corrected for response bias. Correct responses are those that were identified correctly by the participant. A negative response means that the number of answered correctly was less that those answered incorrectly.
Measured: Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2016 (estimated)
- Study startNov 2016
- Primary completion6 Feb 2018
- Study completion6 Feb 2018
Why it stopped: Study stopped due to funding limitations
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.
- Other trials for DepressionStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Columbia University
- Responsible party
- Principal investigator, Bret Rutherford, New York State Psychiatric Institute
- Investigators
- Bret Rutherford, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02943096
- Sponsor's protocol ID
- 7368
- Acronym
- Flavanol
- Status last verified
- Sep 2019
- First submitted
- 18 Oct 2016
- Last updated
- 6 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Flavanol Augmentation for Antidepressant Non-Responsive Late Life Depression
- ClinicalTrials.gov ID
- NCT02943096
- Acronym / sponsor ID
- Flavanol / 7368
- Conditions
- Depression, Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped due to funding limitations
- Enrolment
- 6 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Columbia University
- Study start
- Nov 2016 (actual)
- Primary completion
- 6 Feb 2018 (actual)
- Study completion
- 6 Feb 2018 (actual)
- First posted
- 24 Oct 2016 (estimated)
- Results
- Posted 6 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this proposal is to conduct the first pilot study of whether consuming flavanol supplements will augment the cognitive and mood benefits of antidepressant medication in older adults with Late LifeDepression (LLD). Flavanols represent a specific group of plant derived nutrients that are found in cocoa beans, grapes, tea, berries and various other fruits and vegetables. The specific flavanols investigated in this study come from cocoa. Currently available treatments for LLD (i.e., antidepressant medication) are limited in efficacy, especially in individuals who also suffer from cognitive impairment. Recent studies performed at Columbia and elsewhere suggest that flavanols may induce beneficial brain changes that support cognitive functioning and elevate mood, but their precise clinical effects in older adults with combined depression and cognitive impairment remain to be evaluated. For this study, the investigators plan to recruit 50 adults aged ≥60 years who have Major Depressive Disorder, meet a minimum depressive symptom threshold despite currently receiving an adequate trial of an antidepressant, and have a significant cognitive complaints without a diagnosis of dementia. Subjects will be randomized to receive 8 weeks of augmentation treatment with flavanol capsules (in addition to continuing their antidepressant) vs. capsules not containing flavanols. Pre- and post-treatment MRI scanning of the brain will be conducted, and comprehensive pre- and post-treatment neuropsychological assessment will be performed. Results from this project will allow the investigators to evaluate a novel therapeutic approach to LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD.
Detailed description
The goal of this proposal is to conduct the first pilot study of whether consuming a diet high in flavanols will augment the cognitive and mood benefits of antidepressant medication in older adults with Late Life Depression (LLD). LLD affects 3% of community-dwelling adults over 60 years old, and 15% of older adults living in the community have clinically significant depressive symptoms. Diagnosis with LLD increases an older adult's risk of disability by 67-73% over 6 year follow up, causes twice the functional impairment compared to those without LLD, and is associated with high rates of completed suicide in individuals over 65. Currently available treatments for LLD (i.e., antidepressant medication) are limited in efficacy, leading to high rates of recurrence and frequent development of chronicity. Cognitive impairment, which is commonly associated with LLD, predicts poor acute response to antidepressants, leads to higher relapse rates during the continuation phase of treatment, and is associated with the development of adverse age-related health outcomes, including increased risk of dementia, dependence in activities of daily living (ADL), and driving cessation.
Novel treatments addressing LLD's underlying neurobiology are critically needed, particularly therapies that may also have beneficial effects on the cognitive components of LLD. The most extensively studied brain region to be implicated in both the depressive and cognitive aspects of LLD has been the hippocampus. Decreased hippocampal volumes are found in depressed patients compared to controls, and this finding appears to be particularly pronounced in individuals with recurrent depressive illness. Among the subregions comprising the hippocampus, evidence suggests that it is decreased neurogenesis within the dentate gyrus (DG) specifically that may contribute to the development of depression, and it appears that part of the mechanism of action of antidepressants is to enhance neurogenesis in the DG. As the DG is also a critical contributor to the cognitive functions of the hippocampus, it stands out as a highly significant brain region that may be involved with both the mood and cognitive components of LLD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Flavanol | Active comparator | Dietary Supplement: CocoaViaBlinded treatment with either CocoaVia 500mg or placebo. |
| Placebo | Placebo comparator | Other: PlaceboBlinded treatment with either CocoaVia 500mg or placebo. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women aged ≥60 years (Method of ascertainment: clinical interview)
- DSM 5 diagnosis of Major Depressive Disorder (Method of ascertainment: SCID, clinical interview)
- Subjective report of memory or thinking problems (Method of ascertainment: clinical interview)
- 24-item Hamilton Rating Scale for Depression ≥16 (Method of ascertainment: HRSD)
- Failure of depressive symptoms to remit following an adequate trial of an antidepressant (defined as at least 8 weeks of treatment, with 4 weeks of at least half PDR maximum dose, of an FDA approved antidepressant) (Method of ascertainment: clinical interview)
Key exclusion criteria (11 listed)
- Diagnosis of Substance Use Disorder within the past 12 months (excluding Tobacco) (Method of ascertainment: SCID, clinical interview)
- History of psychosis, psychotic disorder, mania, or bipolar disorder (Method of ascertainment: SCID, clinical interview)
- HRSD suicide item > 2 or CGI =7 at baseline (Method of ascertainment: HRSD, CGI)
- Diagnosis of probable or definite dementia (Alzheimer's Disease, Vascular Dementia, Parkinson's disease, etc.) (Method of ascertainment: SCID, clinical interview, MMSE)
- MMSE ≤24 (Method of ascertainment: MMSE)
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 |
|---|---|---|
| CocoaViaFlavanols represent a specific group of plant derived nutrients that are found in cocoa beans, grapes, tea, berries and various other fruits and vegetables. The specific flavanols investigated in this study come from cocoa. | Dietary supplement | Flavanol |
| PlaceboThe placebo looks like the other intervention pills, but does not contain any flavanols (it is sometimes called a "sugar pill"). | Other | Placebo |
Primary outcome
Hamilton Rating Scale of Depression (HRSD)
Time frame: Week 8
Scale for depressive symptoms administered by trained rater. The HRSD is the standard measure of depression severity for clinical trials of antidepressants and was chosen as the primary outcome measure over other depression rating scales to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. Although the HRSD list 21 items, the scoring is based on the first 24 items. The minimum score is 0 and the maximum score is 74. The higher the number the worse outcome.
4 secondary outcomes
Mnemonic Similarity Task (MST)
Time frame: Baseline
Modified-Benton Task (ModBent)
Time frame: Week 8
Modified-Benton Task (ModBent)
Time frame: Baseline
Mnemonic Similarity Task (MST)
Time frame: Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Bret Rutherford, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CocoaVia in people with Depression and Major Depressive Disorder, 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 6 inclusion and 11 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: stopped early, as of the sponsor's last update on 6 Sep 2019. 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 6 Sep 2019). 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?
Hamilton Rating Scale of Depression (HRSD) (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Sep 2019; AzTrials last refreshed its copy on 30 Oct 2026.