Pilot Study to Investigate the Safety and Feasibility of Senolytic Therapy to Modulate Progression of Alzheimer's Disease (SToMP-AD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Brain Penetrance of Dasatinib (D)
研究概览
简要总结
The purpose of this pilot study is to evaluate whether a combination of two drugs, dasatinib (D) and quercetin (Q) [D+Q], penetrate the brain using cerebrospinal fluid (CSF) in older adults with early Alzheimer's disease (AD). This combination of drug therapy has been shown to affect dying cells in humans with other chronic illnesses and in Alzheimer's mice models. The study team want to know if this combination of medications will reach the brain in order to evaluate if this intervention may be effective for treating AD symptoms in future studies. This is also known as a "proof of concept" study.
详细描述
Up to 40 potential candidates will be pre-screened to identify eligible men and women ages 65 years and over with a clinical diagnosis of early AD on a stable dose of cholinesterase inhibitors for at least 3 months (for example, Aricept).
Eligible participants will undergo laboratory assessments of blood and urine, receive study medications over a twelve week period, and complete pre- and post-treatment testing including: an MRI for digital imaging of the brain; lumbar puncture to obtain cerebrospinal fluid; memory and thinking assessments; quality of life questionnaires; and tests of walking, balance and strength, all of which will be done for research purposes only.
Participants must be accompanied by a Legally Authorized Representative and have no travel plans for 4-5 months that would interfere with study visits.
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 65 years or above.
- •Clinical diagnosis of AD (MoCA 10-20 and Clinical Dementia Rating Scale/CDR = 1) on a stable dose of cholinesterase inhibitors for at least three months
- •Body Mass Index (BMI) within range of 19 - 35 kg/ m2
- •Labs: Normal blood cell counts without clinically significant excursions (WBCs: 4,500-10,500 cells/mcL; absolute neutrophil count: 1,800-8,700 cells/mcL; platelets: 140-450 K/uL; hemoglobin 12.0-17.5 grams/dL); liver and renal function (AST 10-40 IU/L, total bilirubin 0.1-1.4 mg/dl); cholesterol (<240 mg/dl), triglycerides (<300 mg/dl), and glucose control (HbA1c < 7%). PT/PTT/INR within normal limits
- •Participants must be accompanied by a Legally Authorized Representative designated to sign informed consent and to provide study partner reported outcomes at all remaining visits
- •Participants must have no plans to travel over the next 4-5 months that interfere with study visits following consent
排除标准
- •Hearing, vision, or motor deficits despite corrective devices;
- •Alcohol or drug abuse;
- •MRI contraindications;
- •Myocardial infarction, angina, stroke or transient ischemic attack in the past 6 months; QT interval >440 on ECG will not be enrolled. Chronic heart failure will be exclusionary;
- •Participants with coagulation disorders;
- •Neurologic, musculoskeletal, or other condition that limits subject's ability to complete study physical assessments;
- •Uncontrolled diabetes (HbA1c > 7% or the current use of insulin);
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities;
- •Use of anti-arrhythmic medications known to cause QTc prolongation, anti-platelet or anti-coagulant medication;
- •Current use of quinolone antibiotics.
- •Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg).
- •Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and psychiatric disease.
- •History of or MRI-positive for any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindication to lumbar puncture
研究组 & 干预措施
Intermittent D+Q
Senolytic treatment in 5 individuals with early AD to determine levels of drug that reach the central nervous system (CNS) by collecting cerebral spinal fluid (CSF), and begin collecting initial data on target engagement of senescent cells, AD-related markers, and AD-relevant outcomes for future trials.
干预措施: Dasatinib + Quercetin (Drug)
结局指标
主要结局
Brain Penetrance of Dasatinib (D)
时间窗: Change from 0 to 12 weeks
Cerebrospinal Fluid (CSF) collected by lumbar puncture before and after 12 weeks of treatment to determine levels of drug that reach the central nervous system will be measured by high performance liquid chromatography/mass spectrometry (HPLC/MS)
Brain Penetrance of Quercetin (Q)
时间窗: Change from 0 to 12 weeks
CSF collected by lumbar puncture before and after 12 weeks of treatment to determine levels of drug that reach the central nervous system using HPLC/MS
次要结局
- Alzheimer's Disease Marker - CSF Tau(Change from 0 to 12 weeks)
- Alzheimer's Disease Marker - CSF Amyloid Beta(Change from 0 to 12 weeks)
- Senescence Marker IL-6 in CSF(Change from 0 to 12 weeks)
- Senescence Marker P16 in CSF(Change from 0 to 12 weeks)
- Electronic Gait Mapping Under Single and Dual-task Conditions(Change from 0 to 12 weeks)
- Montreal Cognitive Assessment (MoCA)(Change from 0 to 12 weeks)
研究者
Mitzi Gonzales, PhD
Associate Professor
The University of Texas Health Science Center at San Antonio