Flavanol Augmentation for Antidepressant Non-Responsive Late Life Depression
关键词
抽象
描述
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.
日期
| 最后验证: | 08/31/2019 |
| 首次提交: | 10/17/2016 |
| 提交的预估入学人数: | 10/19/2016 |
| 首次发布: | 10/23/2016 |
| 上次提交的更新: | 09/03/2019 |
| 最近更新发布: | 09/05/2019 |
| 首次提交结果的日期: | 04/03/2019 |
| 首次提交质量检查结果的日期: | 09/03/2019 |
| 首次发布结果的日期: | 09/05/2019 |
| 实际学习开始日期: | 10/31/2016 |
| 预计主要完成日期: | 02/05/2018 |
| 预计完成日期: | 02/05/2018 |
状况或疾病
干预/治疗
Dietary Supplement: Flavanol
Other: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Active Comparator: Flavanol Blinded treatment with either CocoaVia 500mg or placebo. | Dietary Supplement: Flavanol 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. |
| Placebo Comparator: Placebo Blinded treatment with either CocoaVia 500mg or placebo. | Other: Placebo The placebo looks like the other intervention pills, but does not contain any flavanols (it is sometimes called a "sugar pill"). |
资格标准
| 有资格学习的年龄 | 60 Years 至 60 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria - 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) Exclusion Criteria - 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) - 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) |
结果
主要结果指标
1. Hamilton Rating Scale of Depression (HRSD) [Week 8]
次要成果指标
1. Mnemonic Similarity Task (MST) [Baseline]
2. Modified-Benton Task (ModBent) [Week 8]
3. Modified-Benton Task (ModBent) [Baseline]
4. Mnemonic Similarity Task (MST) [Week 8]
