APOE Genotype Effects on Triglycerides and Blood Flow in the Human Brain
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Difference in global cerebral blood flow between baseline and 2 hours post lipid ingestion (Change CBF)
研究概览
简要总结
High fat feeding (HFF) increases the risk of Alzheimer's disease (AD) but individuals who carry the AD risk gene E4 paradoxically improve after acute HFF. The investigators propose to further study this phenomenon with a clinical study to assess cerebral blood flow which can be measured by a technique called arterial spin labeling (ASL) on an MRI and is tightly related to brain metabolism.
详细描述
Overview: The purpose of the study is to enroll 90 older adults, half of whom will have E4 carrier status, to assess whether E4 status affects change in global cerebral blood flow (∆CBF) in response to a high fat drink. The screening visit includes informed consent, baseline blood draw, oral triglyceride tolerance test (OTTT), and dual-energy x-ray absorptiometry (DEXA). The study visit involves assessing cerebral blood flow using arterial spin labeling (ASL) MRI - at baseline and at 2 hours after drinking heavy cream. The study visit will also include 6 blood draws and a 30 minute cognitive battery.
Screening Visit Procedures (at Seattle South Lake Union campus): Before the screening visit, participants will receive a copy of the consent form in the mail as well as a medical history questionnaire to fill out. Participants will be advised to fast the night before the screening visit (minimum 8 hours required). After an informed consent process, study personnel will check vitals, including waist circumference, height, and weight for body mass index (BMI) calculation. An IV will be placed by the study nurse and blood sent for complete blood count, chem20 (including liver and kidney function assessment), glycated hemoglobin (hemoglobin A1C), lipid panel, and a blood sample for APOE genotyping (Northwest Lipids using polymerase chain reaction (PCR) methodology). Blood samples except APOE will be sent to the University of Washington (UW) Clinical Laboratory Improvement Amendment (CLIA)-certified lab, and participants will receive a copy of the results by mail. After the blood draw, participants will then undergo an oral glucose tolerance test (OGTT): 6 time points (0, 15, 30, 45, 60,120 min) which will include a blood draw for plasma to measure insulin and C peptide (in batches by Northwest (NW) lipids). At time 0 and 120 minutes study personnel will also assess vitals and a point of care glucose using a glucometer. The OGTT will be the standard 75 grams glucose drink from central supply. After the 2-hour OGTT is complete, patients will undergo a DEXA scan. Note, DEXA can be performed before OGTT if needed for study flow. Parking will be provided, and participants will be paid with a gift card.
Screening visit sample day:
8 am: Check in to the clinic 8-8:30: informed consent in private room, go over medical history 8:30-9: Insert IV, fill out depression, anxiety screen, draw baseline blood 9 -11 am: OGTT (During gaps in OGTT, do Montreal Cognitive Assessment (MoCA)) 11-11:25 am: DEXA 11:25-11:30: Remove IV, distribute gift card and parking validation Time: 3.5 hours, total blood drawn 40 mls
Study Visit Procedures (at University of Washington main campus): Participants will arrive to the UW Translational Research Unit (TRU) after an overnight fast (minimum 8 hours required). The study nurse will place an IV, and check vital signs including blood pressure, heart rate, temperature, and weight. Then, the participant will be escorted to the MRI scanner and undergo the fasting imaging protocol. The participant will head back to the TRU and start the oral triglyceride tolerance test (OTTT). Time 0 blood is drawn and time documented. Then, the participant will drink the dairy product-100 mLs of heavy cream (just under half a cup) which contains 370 calories, 40.4 grams of total fat, 23.6 grams of saturated fat. The participant will be encouraged to drink the product over 5 minutes as per published OTTT protocols. Blood draws will be collected for measurement of glucose, insulin, lipids and appetite hormones (30, 120, 180, 240 min). A post-lipid MRI will be done at the 2 hour time point, and the NIH toolbox cognitive assessment will be done at 3 hour time point. The NIH battery takes approximately 30 minutes to administer and will be done on a portable tablet.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 55 or older at the date of the screening visit
- •Equal representation of APOE E4 carriers and non-carriers
- •Strive for equal numbers of men and women; women need to be post-menopausal for at least 1 year or medical equivalent (hysterectomy)
- •Able to read and understand English
- •Able to cognitively and physically give informed consent 6.Able to undergo an MRI and ingest dairy products
排除标准
- •Diabetes requiring medication: Known type 1 or type 2 diabetes requiring oral diabetic medications or insulin. Diet-controlled diabetes, 'pre-diabetes,' remote use of diabetic agents, or a history of gestational diabetes is ok to enroll.
- •Hypertension requiring medication: Participants taking medication for hypertension will be excluded, unless they can safely stop the medication for 2 weeks, per their primary care provider, before the study visit (The MRI visit).
- •Significant lipid abnormalities: Diagnosis of hyperlipidemia requiring statin, bile acid resins, fibrate medications, and/or high dose niacin will be excluded. If participants are willing to stop their medications 4 weeks before the screening visit (as long as they are not on medication for secondary prevention of heart attack or stroke), this is ok. If participants are taking over-the-counter medications known to affect lipid metabolism including omega-3 fatty acids, niacin, or red yeast rice, they can enroll if they agree to stop the medication 4 weeks before the screening visit. Also excluded are significant cholesterol abnormalities as defined by the 2018 American College of Cardiology/American Heart Association (ACC/AHA) lipid guidelines including a fasting LDL cholesterol ≥190 mg/dL or fasting triglycerides > 500 mg/dL. Total cholesterol levels and HDL levels outside of the typical range are ok.
- •Dementia and cognitive impairment: Known diagnosis of dementia, use of dementia medications, or identification of dementia during the baseline visit, will be excluded. Also excluded are other significant neurologic diseases which affect cognition, such as recent stroke, recent severe head injury, or advanced Parkinson's disease. Mild cognitive impairment with no functional deficits is ok.
- •Psychiatric disorders: Participants who report active untreated major depression, psychosis, or mania, or who present with those symptoms at the baseline visit, or who act belligerent or unprofessional toward the clinical staff, will be excluded. Psychiatric conditions which are stable and treated with medication or therapy are ok. Similarly, individuals who meet criteria for active alcohol or drug abuse disorder will also be excluded as many of these substances could affect the study outcome.
- •Other significant medical illnesses: Illnesses which would cause a hardship on the participant to attend study visits and undergo a glucose tolerance test and an MRI. This includes unstable angina, moderate or severe chronic obstructive pulmonary disease (COPD), class III-IV Congestive heart failure (CHF), active liver or kidney disease causing cognitive symptoms, active cancer undergoing systemic chemotherapy or radiation, as well as other illnesses which in the study physician's view would put the participant at risk and also may place an undue burden on the participant.
- •Major digestive disorders: Disorders which would affect fat tolerance and absorption will be excluded including inflammatory bowel disease, gastric bypass or banding, or small intestine resection. Also excluded are allergies or major intolerance to milk or dairy products.
- •Contraindications to MRI: Metal in body that is not compatible with an MRI, other conditions that preclude an MRI (such as not being able to lie still or lie flat for an extended time) are excluded.
研究组 & 干预措施
Intervention
All participants undergo the same intervention: Drinking heavy cream and undergoing MRI.
干预措施: Heavy Cream (Dietary Supplement)
结局指标
主要结局
Difference in global cerebral blood flow between baseline and 2 hours post lipid ingestion (Change CBF)
时间窗: 2 Hour Change
Change in global cerebral blood flow (CBF) in ml/100g/min, calculated as the subtracted difference between the pre- and the post-ASL flow in response to the intervention.
次要结局
- Change in regional CBF(2 Hour Change)
- Fluid Cognitive Composite Standard Score(3 hours post-drink ingestion)
研究者
Angela Hanson
Assistant Professor, School of Medicine
University of Washington