Study of Nasal Insulin to Fight Forgetfulness - Combination Intranasal Insulin and Empagliflozin Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0
研究概览
简要总结
The proposed pilot study will provide safety and efficacy preliminary data regarding singular and combined effects of two therapeutic approaches, intranasal insulin and treatment with the sodium-glucose cotransporter type 2 inhibitor (SGLT2i) empagliflozin, to correct bioenergetic and vascular dysfunction in adults with preclinical Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) or early AD.
详细描述
The study will consist of a single site, randomized, double-blind trial comparing the effects of 4 weeks of intranasal insulin(40 International Units four times daily), empagliflozin (10 mg daily) and combined intranasal insulin (INI) and empagliflozin (empa) compared with placebo on cerebrospinal fluid (CSF) biomarkers and cognition.
At study entry, participants will be randomized to one of 4 conditions: INI, empa, INI+empa or placebo. Participants who are cognitively normal but have abnormal elevations of brain amyloid or who have mild cognitive impairment (MCI) or early Alzheimer's disease (AD) will be enrolled.
The primary outcome measure will consist of safety (treatment-related serious adverse events). Secondary outcome measures will consist of cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral blood flow.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Neither participants nor site personnel involved in assessing participants will know which dose of insulin is being administered. Exceptions will be the study nurse who is directly involved in preparing the insulin.
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
- 是
入选标准
- •Age 55 to 85 (inclusive)
- •Fluent in English
- •Cognitively normal or diagnosis of amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD)
- •Amyloid positive by positron emission tomography (PET) or cerebrospinal fluid (CSF) criteria
- •Stable medical condition for 3 months prior to screening visit
- •Stable medications for 4 weeks prior to the screening and study visits (exceptions may be made on a case by case basis by the study physician)
- •Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician
排除标准
- •A diagnosis of dementia other than Alzheimer's disease (AD)
- •History of a clinically significant stroke
- •Current evidence or history in past two years of epilepsy, head injury with loss of consciousness, any major psychiatric disorder including psychosis, major depression, 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
- •History of seizure within past five years
- •Pregnancy or possible pregnancy
- •Use of anticoagulants, unless documentation received from prescribing clinician that anticoagulant medication can be held before lumbar puncture, and approved by study clinician
- •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 the study physician)
研究组 & 干预措施
Intranasal Insulin and Empagliflozin Placebo
- 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Placebo capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Aptar Pharma CPS Intranasal Delivery Device (Device)
Intranasal Insulin and Empagliflozin Placebo
- 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Placebo capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Insulin (Humulin® R U-100) (Drug)
Intranasal Insulin and Empagliflozin Placebo
- 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Placebo capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Placebo (Capsules) (Drug)
Empagliflozin and Intranasal Insulin Placebo
- Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
- 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
干预措施: Empagliflozin 10 MG (Drug)
Empagliflozin and Intranasal Insulin Placebo
- Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
- 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
干预措施: Aptar Pharma CPS Intranasal Delivery Device (Device)
Empagliflozin and Intranasal Insulin Placebo
- Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
- 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
干预措施: Placebo (Insulin Diluent) (Drug)
Intranasal Insulin and Empagliflozin
- 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Insulin (Humulin® R U-100) (Drug)
Intranasal Insulin and Empagliflozin
- 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Empagliflozin 10 MG (Drug)
Intranasal Insulin and Empagliflozin
- 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Aptar Pharma CPS Intranasal Delivery Device (Device)
Placebo
- 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Placebo capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Aptar Pharma CPS Intranasal Delivery Device (Device)
Placebo
- 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Placebo capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Placebo (Insulin Diluent) (Drug)
Placebo
- 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
- Placebo capsules taken by mouth 30 minutes before breakfast once daily
干预措施: Placebo (Capsules) (Drug)
结局指标
主要结局
Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0
时间窗: Week 8
Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE v5.0). The number of participants with grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment will be reported.
次要结局
- Change in the Preclinical Alzheimer Cognitive Composite V5 (PACC5) Z-Score(Baseline to Week 4)
- Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score(Baseline to Week 4)
- Change in Amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)(Baseline to Week 4)
- Change in Amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)(Baseline to Week 4)
- Change in Cerebrospinal Fluid (CSF) Levels of Total Tau(Baseline to Week 4)
- Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181(Baseline to Week 4)
- Change in Total Cerebral Blood Flow (CBF) Using MRI Pseudocontinuous Arterial Spin Labeling (ASL)(Baseline to Week 4)