Flavanol Augmentation for Antidepressant Non-Responsive Late Life Depression
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Hamilton Rating Scale of Depression (HRSD)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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)
研究组 & 干预措施
Placebo
Blinded treatment with either CocoaVia 500mg or placebo.
干预措施: Placebo (Other)
Flavanol
Blinded treatment with either CocoaVia 500mg or placebo.
干预措施: CocoaVia (Dietary Supplement)
结局指标
主要结局
Hamilton Rating Scale of Depression (HRSD)
时间窗: 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.
次要结局
- Mnemonic Similarity Task (MST)(Week 8)
- Modified-Benton Task (ModBent)(Baseline)
- Mnemonic Similarity Task (MST)(Baseline)
- Modified-Benton Task (ModBent)(Week 8)
研究者
Bret Rutherford
Associate Professor of Clinical Psychiatry
New York State Psychiatric Institute