Pilot Phase 2 Trial of the Safety & Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor (Leukine®) in the Treatment of Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Adverse Events (AEs) by Body System
研究概览
简要总结
A medicine that is FDA-approved for bone marrow stimulation (called Leukine) will be tested for its ability to be tolerated by Alzheimer's disease patients and potentially to improve their memory.
详细描述
Preliminary preclinical results demonstrated that GM-CSF (Granulocyte macrophage colony-stimulating factor, e.g. Leukine®/Sargramostim) rapidly reduced cerebral amyloid deposition and completely reversed memory deficits in transgenic mouse models of Alzheimer's Disease (AD). To assess the efficacy of GM-CSF in humans, the investigators performed a retrospective analysis of a cognition study of human patients undergoing hematopoietic cell transplantation for cancer and who garner cognitive impairments from the chemotherapy or irradiation. In the patients that received a colony-stimulating factor (CSF) to stimulate the bone marrow and recover immune system function, the investigators found that those who received GM-CSF (Leukine®/Sargramostim) plus G-CSF (Filigrastim) significantly improved in cognitive function as compared to those who received G-CSF alone. These findings combined with over two decades of accrued safety data using recombinant human GM-CSF, Leukine®/Sargramostim, in elderly leukopenic patients, suggested that Leukine® should be tested as a treatment to reverse cerebral amyloid pathology and cognitive impairment in AD.
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
- Triple (Participant, Care Provider, Investigator)
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
- •age 55 to 85 years;
- •should have a mild-to-moderate AD diagnosis (MMSE 10-26 inclusive);
- •should have evidence of elevated cortical amyloid by PET using florbetapir F18 (Amyvid) [i.e. a positive scan], assessed qualitatively according to the Amyvid product label.
- •if on anti-dementia treatment should be on stable treatment for at least 2 months (i.e. cholinesterase inhibitor and/or Memantine or Axona);
- •stable on all other medications for at least 30 days prior to screen;
- •should be fluent in English;
- •should be physically able to participate by medical history, clinical exam and tests;
- •should have a study partner to accompany them to scheduled visits.
排除标准
- •clinically relevant arrhythmias;
- •a resting pulse less than 50;
- •active cancer other than non-melanoma skin cancers;
- •use of another investigatory drug within 2 months of screening;
- •significant stroke or head trauma by history or MRI;
- •contraindication for having a MRI;
- •diagnostic and Statistical Manual of Mental Disorders-IV criteria for a current major psychiatric disorder;
- •sensitivity to yeast or yeast products;
- •impaired kidney function as measured by a Glomerular Filtration Rate less than 60 milliliters/min;
- •preexisting fluid retention, pulmonary infiltrates, or congestive heart failure;
- •history of moderate-to-severe lung disease;
- •history of moderate-to-severe liver disease;
- •pregnant women, or any women who feel they are likely to become pregnant during the study;
研究组 & 干预措施
Sagramostim (Leukine)
5 subjects 250 mcg /m2/day Leukine subcutaneously for 5 days/week for three weeks. Data and Safety Monitoring Board will then review data and recommend whether to continue at the same current recommended dose for additional subjects or to reduce the dose by half if excessive leukocytosis occurs
干预措施: Sagramostim (Drug)
Control Group
Saline -- placebo comparator. Given as a subcutaneous injection.
干预措施: Saline -- placebo comparator (Drug)
结局指标
主要结局
Adverse Events (AEs) by Body System
时间窗: 20 weeks (From Consent to Follow-up 2)
Count of AE's from Consent to Follow-up 2 within a safety analysis set consisting of all participants who were enrolled and randomized and who received at least one injection of sargramostim or placebo
次要结局
- MMSE (Mini Mental State Examination) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)(From Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment))
- Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)(Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment))