REstoring Vascular and Insulin Function To Augment Anti-Amyloid Therapy in ALZheimer'ss Disease (REVITAA-ALZ): A Placebo-controlled Trial of Intranasal Insulin vs. Empagliflozin in Mild Cognitive Impairment (MCI) or Early Alzheimer's Disease (AD) Treated With Anti-Amyloid Targeting Therapy (Lecanemab or Donanemab)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of treatment-related serious adverse events
研究概览
简要总结
The purpose of this study is to find out what effects (good and bad) the study medications (insulin or Empagliflozin) have on adults with mild memory impairment or early Alzheimer's disease who are clinically prescribed an anti-amyloid therapy compared to placebo.
详细描述
The proposed pilot study will evaluate the efficacy, safety and tolerability of two therapeutic approaches: treatment with intranasal insulin in combination with anti-amyloid targeting therapy (ATT) and treatment with the sodium-glucose cotransporter type 2 inhibitor empagliflozin in combination with ATT, to correct bioenergetic and vascular dysfunction in adults with mild cognitive impairment due to Alzheimer's disease or mild dementia due to Alzheimer's disease.
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, Care Provider)
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
- •Fluent in English
- •Diagnosis of mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease via previously documented clinical assessment
- •Amyloid positive by PET or cerebrospinal fluid criteria
- •Stable medical condition for 3 months prior to screening visit
- •Stable medications for general medical conditions for 4 weeks prior to the screening and study visits (exceptions may be made on a case-by-case basis by study clinician)
- •Stable on Anti-Amyloid Targeting Therapy (lecanemab or donanemab) for at least 8 weeks prior to Baseline Visit
- •If receiving an acetylcholinesterase inhibitor (donepezil, rivastigmine, galantamine) or memantine or both, must be stable on a dose for at least 30 days prior to Baseline Visit
- •Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study clinician
- •Participants must have a study partner who agrees to participate throughout the duration of the study. The study partner must have frequent and sufficient contact (approximately 10 hours per week) with the participant and be able to provide accurate information regarding the participant's cognitive and functional abilities.
排除标准
- •A diagnosis of dementia other than Alzheimer's disease
- •History of a clinically significant stroke, history of transient ischemic attack within 12 months, or any history of seizures
- •Current evidence or history in past two years of head injury with loss of consciousness, any major psychiatric disorder including psychosis, unstable major depressive disorder, bipolar disorder
- •Diabetes (type I or type II) insulin dependent and non-insulin dependent diabetes mellitus
- •Current or past regular use of insulin or any other anti-diabetic medication within 2 months of screening visit
- •Cancer within the past 2 years with the exception of non-melanoma skin cancers and non-metastatic prostate cancer that has been stable for at least 6 months
- •Pregnancy or possible pregnancy
- •Use of anticoagulants
- •Residence in a skilled nursing facility at screening
- •Use of an investigational agent within two months of screening visit
- •Regular use of alcohol, narcotics, anticonvulsants, anti-Parkinsonian medications, or any other exclusionary medications (exceptions may be made on a case-by-case basis by study clinician)
- •Any history of immunologic disease (e.g. lupus, rheumatoid arthritis, Crohn's disease) or systemic treatment with immunosuppressants, immunoglobulins, or monoclonal antibodies or their derivatives
- •History of a bleeding disorder that is not under adequate control, including a platelet count less than 50,000 or INR greater than 1.5
- •Contraindications for MRI, including claustrophobia or the presence of contraindicated metal implants/cardiac pacemaker
- •Baseline MRI Findings: More than four microhemorrhages defined as 10mm or less at the greatest diameter; A single macro hemorrhage greater than 10mm at greatest diameter; An area of superficial siderosis; Evidence of vasogenic edema; More than two lacunar infarcts or stroke involving a major vascular territory; Severe subcortical hyperintensities consistent with Fazekas score of 3; Evidence of amyloid beta-related angiitis (ABRA); Cerebral amyloid angiopathy (CAA); Cerebral contusion, encephalomalacia, brain aneurysm or other vascular malformations, central nervous system infection, brain tumor, or other major intracranial pathology that may cause cognitive impairment
研究组 & 干预措施
Empagliflozin and Insulin Matching Placebo
empagliflozin 10 mg every day and intranasal insulin matching placebo as add-on treatment to anti-amyloid therapy
干预措施: Empagliflozin (Drug)
Empagliflozin and Insulin Matching Placebo
empagliflozin 10 mg every day and intranasal insulin matching placebo as add-on treatment to anti-amyloid therapy
干预措施: Insulin Placebo (Drug)
Double Placebo
Placebo for intranasal insulin and placebo for empagliflozin as add-on treatment to anti-amyloid therapy
干预措施: Insulin Placebo (Drug)
Double Placebo
Placebo for intranasal insulin and placebo for empagliflozin as add-on treatment to anti-amyloid therapy
干预措施: Empagliflozin Placebo (Drug)
Insulin and Empagliflozin Matching Placebo
Intranasal insulin 40 international units four times daily and empagliflozin matching placebo as add-on treatment to anti-amyloid therapy
干预措施: Empagliflozin Placebo (Drug)
Insulin and Empagliflozin Matching Placebo
Intranasal insulin 40 international units four times daily and empagliflozin matching placebo as add-on treatment to anti-amyloid therapy
干预措施: Insulin (Drug)
结局指标
主要结局
Number of treatment-related serious adverse events
时间窗: Month 6
Number of treatment related serious adverse events experienced by participants during course of study
次要结局
- Alzheimer's Disease Assessment Scale-Cognition Score(baseline and month 6)
- Modified Preclinical Alzheimer Cognitive Composite 5 Score(baseline and month 6)
- Montreal Cognitive Assessment Score(baseline and month 6)
- Clinical Dementia Rating Scale Score(baseline and month 6)