Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Number of Dose Limiting Toxicity Events
研究概览
简要总结
The purpose of this study is to determine if oxaloacetate (OAA) is safe and tolerable at doses of up to 2 grams per day in people with Alzheimer's disease (AD).
详细描述
Alzheimer's disease (AD) is a progressive brain disorder that causes memory and thinking problems. The exact cause of AD is unknown. Researchers believe mitochondria (the part of your cells that produce energy) might be linked to symptoms of AD. Some studies have shown that the brains in patients with Alzheimer's disease have reduced mitochondrial activity, have fewer mitochondria present in the nerve cells, and have reduced ability to utilize glucose (sugar) for energy.
Oxaloacetate (OAA) is a natural chemical that has been shown to have an effect on brain mitochondrial activity and brain energy in non-human animals.
This study is divided into two parts. In the first part of the study, researchers will test whether a dose of 1 gram per day of OAA, taken for approximately 4 weeks in 15 people with AD is safe and tolerable. After all 15 participants in part 1 have completed their participation, and it is determined that the study drug was safe at this dose, the second part of the study will begin. In part 2, researchers will test a dose of 2 grams per day of OAA, taken for approximately 4 weeks in 15 people with AD, to assess safety at this dose.
Participants will be in this study for about 10 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of probable Alzheimer's disease (AD) per McKhann et al. criteria [9];
- •Have a clinical dementia rating (CDR) score of 0.5 or 1 at time of their last University of Kansas Alzheimer's Disease Center (KU ADC) assessment;
- •Have a Mini Mental Status Exam (MMSE) score of 15-28 at the TOAD screening visit;
- •Have a reliable and competent study partner who is willing to accompany the participant to all study visits, monitor compliance of study medication administration, and observe/report any changes in the participant's health throughout the study duration;
- •Are on stable doses of concurrent medications for at least 4 weeks prior to the TOAD screening visit; and
- •Speaks English as his/her primary language.
- •If female of child-bearing potential, must have a negative urine pregnancy test at TOAD screening visit (and must agree to use of contraception throughout the trial)
排除标准
- •Dementia due to causes other than AD;
- •Potentially confounding, serious, or unstable medical conditions such as:
- •insulin-dependent diabetes mellitus
- •cancer within the past 3 years (except basal cell, squamous cell, or localized prostate cancer)
- •a recent cardiac event (i.e. heart attack, angioplasty, etc. within the 6 months prior to screening visit)
- •other conditions that pose a potential safety risk or confounding factor in the investigator's opinion;
- •Any abnormal physical examination assessment or vital sign assessment at TOAD screening visit that is deemed to be clinically significant by the principal investigator;
- •Any abnormal clinical laboratory test result at TOAD screening visit that is deemed to be clinically significant by the principal investigator.
- •Any contraindication for undergoing magnetic resonance spectroscopy (MRS), such as the presence of metal implants, a cardiac pacemaker that is not compatible with MRS, or severe claustrophobia
研究组 & 干预措施
Part 1 - Oxaloacetate (OAA) 1 gram/day
Participants take 1 gram of OAA per day for period of 4 weeks
干预措施: Oxaloacetate (OAA) 1g (Drug)
Part 2 - Oxaloacetate (OAA)2 gram/day
Participants take 2 grams of OAA per day for period of 4 weeks
干预措施: Oxaloacetate (OAA) 2g (Drug)
结局指标
主要结局
Number of Dose Limiting Toxicity Events
时间窗: Change from Baseline to Week 4
The number of dose limiting toxicity events will be determined by change in safety labs, physical and neurological exams, vital signs, cognitive measures, signs and symptoms.
次要结局
- Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET)(Change from Baseline to Week 4)
- Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS)(Change from Baseline to Week 4)
- Plasma Levels in 500 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose(Change from dose to 60 min post dose and 90 min post dose)
- Plasma Levels in 1000 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose(Change from dose to 60 min post dose and 90 min post dose)
研究者
Russell Swerdlow
Gene and Marge Sweeney Professor of Neurology
University of Kansas Medical Center