Brain Energy for Amyloid Transformation in AD (BEAT-AD) Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Cerebrospinal Fluid Abeta42
研究概览
简要总结
The Brain Energy for Amyloid Transformation in AD (Alzheimer's disease) or BEAT-AD study will compare the effects of a ketogenic low-carbohydrate diet and a low-fat diet in adults with mild cognitive impairment. The data collected will help determine whether diet interventions induce changes in cognitive function, cerebral blood flow, and levels of certain proteins and hormones in body fluids.
The study will include volunteers who have mild cognitive impairment, who will be randomly assigned to receive either a ketogenic low-carbohydrate diet or a low-fat diet for 16-weeks, with follow-up assessment 8 weeks after diet completion. Study measures, clinic visits and phone sessions will occur at baseline and throughout the 24-week study.
Participant will follow either a low-carbohydrate or low-fat diet that will be individually planned with help from a study dietitian. After completing the study diet for 16 weeks, participants will resume their normal diet. The final visits will occur at week 24 (8 weeks after the completing the diet). At the end of the 24-week study, participants will be given the opportunity to meet with the study dietitian for education and assistance with planning a healthy diet.
详细描述
This study will examine the effects of a 4-month Modified Mediterranean-Ketogenic Diet compared with an American Heart Association Diet (AHAD - a regimen that has been shown to reduce the risk for cardiovascular disease). We will investigate diet effects on AD biomarkers, on cognition, and on neuroimaging measures of blood flow. Our study will extend previous findings in several important ways by: 1) using a Modified Mediterranean-Ketogenic Diet rather than a traditional Ketogenic Diet, which has the potential for greater long-term compliance and health benefits; 2) increasing the sample size and duration of the diet intervention; 3) examining potential mechanisms of diet effects that may result in new biomarkers and therapeutic targets; and 4) examining key treatment response variables such as Apolipoprotein E (ApoE) genotype, amyloid positivity and metabolic status that could inform precision medicine approaches to dietary prescription.
Adults with amnestic mild cognitive impairment (MCI) will be randomized on a 1:1 schedule to receive either a 4-month Modified Mediterranean-Ketogenic Diet (MMKD) or American Heart Association Diet (AHAD) intervention. Diet interventions will be equicaloric with participants' normal diets. Personalized nutritional guidance and menus will be provided, and compliance will be assessed by a registered dietitian. The principal investigator will be responsible for the overall monitoring of the data and safety of study participants, with assistance by members of the study staff, and the Data and Safety Monitoring Board (DSMB), which will be responsible for monitoring the safety of research participants.
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
- Double (Investigator, Outcomes Assessor)
盲法说明
It is not possible for participants and the dietitian to be blinded to the study diet.
Study personnel involved in performing cognitive testing or other outcome procedures or data analysis will be blinded.
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of amnestic mild cognitive impairment
- •An informant (study partner) able to provide collateral information on the participant
- •Stable medical condition (generally 3 months prior to screening visit) at the discretion of study physician
- •Stable on medications (generally 4 weeks prior to screening visit) at the discretion of study physician
- •Able to complete baseline assessments
排除标准
- •Diagnosis of neurodegenerative illness (except for MCI);
- •History of a clinically significant stroke
- •Current evidence or history in past year of focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- •Sensory impairment (i.e.: visual or auditory) that would preclude the participant from participating in the protocol
- •Diabetes that requires current use of diabetes medications
- •Clinically significant elevations in liver function tests
- •Active neoplastic disease (stable prostate cancer and non-melanoma skin cancer is permissible)
- •History of epilepsy or seizure within past year
- •Contraindications for MRI (claustrophobia, craniofacial metal implants, pacemakers)
- •Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease
研究组 & 干预措施
Modified Mediterranean Ketogenic Diet
The MMKD is a low carbohydrate/high fat diet aimed at inducing ketosis, as the experimental diet in the proposed study. Participants on the MMKD will keep their daily carbohydrate consumption below 20 grams per day throughout the 4 month intervention.The MMKD group will be supplied with extra virgin olive oil during their in person visits to use as a source of fat in their diet, and will be encouraged to eat plentiful fish, lean meats, and nutrient rich foods that meet the requirement of <20 grams total carbohydrates per day.
Participants will receive a daily multivitamin (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.
干预措施: low carbohydrate/high fat diet (Other)
American Heart Association Diet
The American Heart Association Diet (AHAD), is a low fat/high carbohydrate diet (<40 grams/day) will be used as the control diet. Participants on the AHAD will be encouraged to limit their amount of fat intake to <40 grams/day, while eating plentiful fruits, vegetables, and carbohydrates containing adequate fiber. Participants will receive the same daily multivitamin supplement (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.
干预措施: low fat/high carbohydrate diet (Other)
结局指标
主要结局
Cerebrospinal Fluid Abeta42
时间窗: baseline
Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
Cerebrospinal Fluid Abeta42
时间窗: week 16
Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
次要结局
- Cerebrospinal Fluid Aβ40(baseline, week 16)
- Cerebrospinal Fluid Total Tau(baseline, week 16)
- Cerebrospinal Fluid ptau181(baseline, week 16)
- Cerebrospinal Fluid NfL(baseline, week 16)
- Plasma Aβ42(baseline, week 16)
- Plasma Aβ40(baseline, week 16)
- Plasma p-tau217(baseline, week 16)
- Plasma Phosphorylated Tau 181(baseline, week 16)
- Plasma NfL(baseline, week 16)
- Hemoglobin A1c(baseline, week 16)
- Triglyceride Level(baseline, week 16)
- LDL Level(baseline, week 16)
- HDL Level(baseline, week 16)
- Total Cholesterol Level(baseline, week 16)
- Ketones Level(baseline, week 16)
- Glucose Level(baseline, week 16)
- MRI Pseudo Continuous Arterial Spin Labeling Hippocampal Uptake(baseline, week 16)
- MRI Pseudo Continuous Arterial Spin Labeling Meta-Region of Interest Uptake(baseline, week 16)
- MRI Neurite Orientation Dispersion and Density Imaging-Neurite Density Index (NODDI-NDI) Hippocampal Uptake(baseline, week 16)
- MRI Neurite Orientation Dispersion and Density Imaging-Neurite Density Index (NODDI-NDI) Meta-Region of Interest Uptake(baseline, week 16)
- MRI Neurite Orientation Dispersion and Density Imaging-Isotropic Volume Fraction (NODDI-ISOVF) Hippocampal Uptake(baseline, week 16)
- MRI Neurite Orientation Dispersion and Density Imaging-Isotropic Volume Fraction (NODDI-ISOVF) Meta-Region of Interest (ROI) Uptake(baseline, week 16)
- MRI Neurite Orientation Dispersion and Density Imaging Orientation Dispersion Index (NODDI-ODI) Hippocampal Uptake(baseline, week 16)
- MRI Neurite Orientation Dispersion and Density Imaging Orientation Dispersion Index (NODDI-ODI) Meta-Region of Interest (ROI) Uptake(baseline, week 16)
- Modified Preclinical Alzheimer Cognitive Composite 5 (mPACC5) Score(Week 16)
- Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog 12) Score(baseline, week 16)
- Neuropsychiatric Inventory Questionnaire (NPI-Q) Score(baseline, week 16)
- Geriatric Depression Scale Score(baseline, week 16)