The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 180
- 试验地点
- 6
- 主要终点
- Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog-11)
研究概览
简要总结
The LUCINDA Trial is a three-site, phase II, randomized, double-blind, placebo-controlled study of leuprolide acetate (Eligard) in women with Mild Cognitive Impairment or Alzheimer's Disease taking a stable dose of a cholinesterase inhibitor medication like donepezil. Its objective is to assess the efficacy of a 48-week regimen of leuprolide (22.5 mg per 12 weeks) compared to placebo on cognitive function, global function and plasma and neuroimaging biomarkers.
详细描述
This project aims to re-purpose the safe and well-tolerated gonadotropin-releasing hormone (GnRH) analogue Leuprolide Acetate for use in Alzheimer's Disease (AD). Leuprolide Acetate is currently used in adults for prostate cancer, endometriosis, uterine fibroids and in preparation for in-vitro fertilization, and in children for central precocious puberty. The purpose of this study to confirm and extend results from a prior phase II study (Bowen et al, 2015) which demonstrated that Leuprolide halted cognitive and functional decline in a subgroup of women with mild-moderate AD who were also taking the acetylcholinesterase inhibitor donepezil. Objectives are to replicate, in the same subgroup, Leuprolide's clinical EFFICACY in this prior trial and to add neuroimaging and plasma BIOMARKERS that will help elucidate Leuprolide's likely multiple mechanisms of action in AD. These mechanisms include decreasing levels of Luteinizing Hormone (LH) based on extensive preclinical evidence that decreasing LH preserves cognition and decreases amyloid deposition and tau phosphorylation in animal models of AD, as well as new evidence that GnRH analogues may have anti-inflammatory effects.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, post-menopausal
- •Probable AD or MCI due to AD according to NIA-AA criteria
- •Taking a stable dose of a cholinesterase inhibitor such as donepezil/Aricept and dosage likely to remain stable throughout the trial
- •MOCA > 11 or blind MOCA > 8 (inclusive) at screening visit
- •Hachinski score <5 supporting clinical judgment that dementia is not of vascular origin
- •Fluent in English
- •has a study partner / caregiver who interacts with the subject for at least 5 hours per week on average and can participate in evaluations
排除标准
- •Presence based on exam, history or MRI of significant brain disease other than AD such as schizophrenia, epilepsy, Parkinson's disease or large territory stroke
- •Current substance abuse in accord with DSM V criteria
- •Significantly depressed (Geriatric Depression Scale > 10)
- •Physical or psychological MRI contraindications, or likely unable to tolerate neuroimaging
- •Taking other medications known to affect serum sex hormone or gonadotropin concentrations such as estrogen and/or progesterone for hormone replacement therapy, goserelin or danazol
- •Presence of significant systemic illness likely to interfere with participation in or completion of the study or to affect study results such as cancer within 5 years (other than non-melanoma skin cancer), autoimmune disease, recent myocardial infarction, signs/symptoms of organ failure based on history, ECG, screening laboratory and/or physical exams
- •Receiving other investigational drugs within 30 days or 5 half-lives prior to randomization, whichever is longer
研究组 & 干预措施
Placebo
0.25 ml of sterile normal saline administered subcutaneously / 12 weeks
干预措施: Placebo (Drug)
Leuprolide
Eligard 22.5mg administered subcutaneously / 12 weeks
干预措施: Eligard 22.5Mg Suspension for Injection (Drug)
结局指标
主要结局
Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog-11)
时间窗: Baseline, 48 Weeks
The ADAS-cog-11 consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of Alzheimer's Disease.
次要结局
- Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)(Baseline, 48 Weeks)
- Change in Brain Magnetic Resonance Imaging (MRI) biomarkers(Baseline, 48 Weeks)
- Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)(Baseline, 48 Weeks)
- Percent change in Burden Inventory(Baseline, 48 Weeks)
- Percent change in Neuropsychiatric Inventory (NPI)(Baseline, 48 Weeks)
- Alzheimer Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC+)(Baseline, 48 Weeks)