Endothelial Facilitation in Alzheimer's Disease. An Open Label Pilot Study of the Sequential and Cumulative Effects of Simvastatin, L-Arginine, and Sapropterin (Kuvan) on Cerebral Blood Flow and Cognitive Function in Patients With Alzheimer's Disease.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
研究概览
简要总结
Purpose of the study: Patients with mild Alzheimer's Disease will be given three different drugs over a 4-month period to try to increase the blood flow to their brains, and improve blood vessel and brain function. Each drug can help to open the blood vessels in the brain, and together they may be more effective than each drug alone. The hypothesis is that small blood vessels secrete substances that maintain the integrity of the brain, and may prevent loss of nerve cells leading to Alzheimer's Disease
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Subjects must have mild Alzheimer's Disease or Mild Cognitive Impairment (MCI);
- •age between 55-85;
- •Mini Mental Status Exam (MMSE) between 15-26;
- •a caregiver who can provide information, and bring patient to the sessions;
- •no known allergies to any of the medications to be used;
- •normal renal function; willingness of patient and spouse/responsible caregiver to participate.
排除标准
- •Significant Psychiatric disorder;
- •stroke; current use of any of the test medications (e.g., statin, L-Arginine, Kuvan);
- •phenylketonuria (PKU) ;
- •elevated serum phenylalanine level (>10 mg/dL);
- •allergy to any of the medications; current active malignancy;
- •renal insufficiency (elevated creatinine above 1.3mg/dl);
- •abnormal liver function (Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) 2x normal);
- •other serious disease including coronary insufficiency or congestive heart failure, carotid stenosis greater than 50%, active peptic ulcer, urinary tract or other active infection, cancer (except skin cancer, or 5 years inactive breast or prostate cancer )etc.;
- •pregnancy; or
- •inability to come to UMass for follow-up. Subjects may continue to take anticholinesterase drugs for Alzheimer's Disease (Aricept, Exelon, Razadyne) and/or Namenda, if they have been on the drug(s) for at least 3 months. Subjects on levodopa and male subjects taking drugs for erectile dysfunction (Viagra, Cialis, Levitra) are cautioned regarding hypotension.
研究组 & 干预措施
Simvastatin + L-Arginine + Tetrahydrobiopterin
Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally
干预措施: Simvastatin (Drug)
Simvastatin + L-Arginine + Tetrahydrobiopterin
Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally
干预措施: L-Arginine (Drug)
Simvastatin + L-Arginine + Tetrahydrobiopterin
Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally
干预措施: Tetrahydrobiopterin (Drug)
结局指标
主要结局
Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
时间窗: Baseline to 16 weeks
Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI)
Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI)
时间窗: Baseline to week 16
Data not available as files corrupted and could not be analyzed
次要结局
- Mini Mental State Examination (MMSE) Scores(Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline)
- Cognitive Assessment Screening Test (CAST)(Baseline to 16 weeks post-baseline)
- Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)(Baseline to 16 weeks post-baseline)
- Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)(Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline)
- Clinical Dementia Rating Scale (CDR)(Baseline to 16 weeks post-baseline)
研究者
Elizabeth Degrush
Assistant Professor, Psychiatry
University of Massachusetts, Worcester