NCT03319810已完成2 期
Proof of Concept of the Effect of Intravenous Immunoglobulin on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Change in Baseline Retinal Amyloid Imaging (RAI) at 3 Months
研究概览
简要总结
This is a proof of concept study to determine if changes in brain amyloid levels are evident three months after infusion of 0.4 g/kg of IVIG every 14 days x 5 infusions. Amyloid levels will be measured by Florbetapir PET and retinal scan.
详细描述
Study design:
This is a single center, open label, proof of concept, out-patient study. Subjects will undergo Florbetapir PET and have retinal amyloid levels measured, receive an infusion of IVIG at 0.4 g/kg every 14 days for a total of five infusions, and repeat PET and retinal amyloid measures three months after the first infusion.
Subject population:
The study population will consist of male and female subjects diagnosed with mild cognitive impairment (MCI) due to Alzheimer disease (AD).
Estimated study duration:
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
- 50 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 50 to <85 years.
- •Evidence of amyloid pathology on Florbetapir PET at screening.
- •Diagnosis of MCI due to AD based on NIA-AA criteria. (APPENDIX A)
- •MRI brain (with past 24 months) which shows evidence of mild hippocampal atrophy and/or bilateral parietal atrophy.
- •CDR score of 0.5
- •Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
- •Rosen Modified Hachinski Ischemic score ≤
- •Receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to screening. Cholinesterase inhibitors and memantine are allowed if doses have stable been least 30 days prior to screening.
- •Agree to refrain from participating in any treatment or clinical trial targeting amyloid for the duration of the study.
- •Agree to refrain from taking any herbal supplement considered to enhance cognition unless approved by the investigator for the duration of the study.
- •Ability to attend all clinical visits and have an informant capable of accompanying the subject on specific clinic visits.
- •The subject's collaborative informant (support person) must be someone who has known the subject for at least 4 years and has had approximately 2 or more separate communications with the study participant per month (at least one of these communications in person).
- •Fluency in English and evidence of adequate premorbid intellectual functioning.
- •Adequate manual dexterity, visual, and auditory abilities to perform all aspects of the cognitive and functional assessments.
- •Venous access suitable for repeated infusions and phlebotomy.
- •In the opinion of the investigator, the subject and informant will be compliant and have a high probability of completing the study, including all scheduled evaluations and required tests.
排除标准
- •Has significant neurological disease other than MCI that in the opinion of the investigator may affect cognition.
- •History of clinically evident stroke or history of clinically significant carotid or vertebrobasilar stenosis or plaque.
- •History of seizures, excluding febrile seizures in childhood.
- •History of screening visit brain MRI scan indicative of any other significant abnormality, including but not limited to multiple microhemorrhages (2 or more), history or evidence of a single prior hemorrhage > 1 cm3, multiple lacunar infarcts (2 or more) or evidence of a single prior infarct > 1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions of significance as determined by the PI (e.g., arachnoid cysts or brain tumors such as meningioma).
- •Brain MRI shows moderate or severe cortical or hippocampal atrophy.
- •Sensitivity to Florbetapir.
- •Other present/planned ionized radiation that, in combination with planned exposure to PET ligands for this study, would result in cumulative exposure that would exceed recommended limits.
- •Ophthalmologic condition that would interfere with retinal amyloid imaging.
- •Current presence of a clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) or symptom (e.g., hallucinations) that in the opinion of the investigator could affect the subject's ability to complete the study.
- •Current clinically significant systemic illness that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study including but not limited to renal failure or myocardial infarction.
- •History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma, and squamous cell carcinoma of the skin.
- •Uncontrolled hypertension (diastolic BP> 100 mmHg or systolic BP> 160 mmHg, sitting).
- •History or evidence of any clinically significant autoimmune disease or disorder of the immune system (e.g., Crohn's Disease, Rheumatoid Arthritis)
- •Clinically significant infection within the last 30 days (e.g., chronic persistent or acute infection (eg, upper respiratory infection [URI], urinary tract infection [UTI]).
- •Female subjects of childbearing potential.
- •Other clinically significant abnormality on physical, neurological, laboratory, vital signs or ECG examination (e.g., atrial fibrillation) that could compromise the study or be detrimental to the subject.
- •Weight greater than 120 kg (264 lbs).
- •Excessive smoking defined as more than 20 cigarettes per day.
- •History of alcohol or drug dependence or abuse as defined by DSM-IV criteria within the last 2 years.
- •Severe liver or kidney disease verified by the PI review of ALT, AST and creatinine.
- •Known coagulopathy, thrombosis, or low platelet count.
- •Hemoglobin less than 11 g/dL.
- •Known deficiency to IgA.
- •Positive serology for Hepatitis B or C, or HIV.
- •History of anti-amyloid treatment, immunotherapy, or other experimental treatment for MCI or Alzheimer disease.
- •Concurrent use of anticholinergic drugs including diphenhydramine.
- •Current use of anticoagulant medications (except the use of aspirin 325 mg/day or less, plavix, aggrenox, and persantine but not for stroke).
- •Concurrent use of opioid pain relievers and related synthetic derivatives.
结局指标
主要结局
Change in Baseline Retinal Amyloid Imaging (RAI) at 3 Months
时间窗: Baseline to 3 months
This is a noninvasive imaging technique that can detect amyloid-beta deposition in the retinas of the eye.
Change in Baseline Standard Uptake Ratio Values (SUVr) of Florbetapir PET at 3 Months
时间窗: Baseline to 3 months
Amyloid deposition in the brain is thought to lead to the development of cognitive decline and conversion to AD. Each participant's amyloid burden can also be quantified through the computation of a Standard Uptake Value ratio (SUVr).
次要结局
未报告次要终点
研究者
Shawn Kile, M.D.
Principal Investigator
Sutter Health
研究点 (2)
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