Long-acting Exenatide: a Tool to Stop Cognitive Decline in Dysglycemic Patients With Mild Cognitive Impairment?
试验速览
- 阶段
- 3 期
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Improvement of ADAS-cog Alzheimer's Disease Assessment Scale defined by ADAS-cog score at 16 (V2) and at 32 weeks (V3) compared to baseline
研究概览
简要总结
The overall objective of the study is to assess the potential effects of the long-acting GLP-1 analogue exenatide in preventing/slowing the progression of cognitive dysfunction and related biomarkers in dysglycemic/prediabetic patients with mild cognitive impairment (MCI).
详细描述
Type 2 Diabetes Mellitus (T2DM) and Alzheimer's Disease (AD) are two of the most common diseases of aging.The presence of T2DM almost doubles the risk of developing AD and is associated with a faster rate of cognitive decline in those with mild cognitive impairment (MCI). Blood glucose levels are directly associated with accelerated cognitive decline also in subjects with impaired fasting glucose and in individuals without clinical DM. Impaired insulin signaling is critically involved in the natural history of both T2DM and AD and it may represent a common mechanistic link ("common soil") between dysglycemic/prediabetic states and AD development and progression.
The overall objective of the study is to assess the potential effects of the long-acting GLP-1 analogue exenatide in preventing/slowing the progression of cognitive dysfunction and related biomarkers in dysglycemic/prediabetic patients with mild cognitive impairment (MCI).
All eligible patients at V0 will undergo baseline assessments (V1) and will be allocated according to the procedure of randomization to one of the study arms. Follow-up (FU) visits for all subjects will be at 16 (V2) and at 32 weeks (V3) after randomization. Additionally, subjects on active treatment will be admitted weekly to the Outpatient Diabetes Unit of the AOUPR for GLP-1 subcutaneous injections and to check for possible side effects. Subjects in the control arm will be seen at the Center for Dementia (AOUPR) according to their usual schedule.
Laboratory and diagnostic:
At each study visits patients will undergo:
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
- None
入排标准
- 年龄范围
- 51 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients capable of giving informed consent
- •dysglycemia/prediabetes defined as fasting plasma glucose between 100 and 125 mg/dl and/or 2-hour plasma glucose between 140 and 199 mg/dl after a 75 g OGTT and/or a HbA1c value between 5.7 and 6.4%
- •diagnosis of MCI according to the Petersen clinical criteria (the expected corrected scores at the MMSE are from 24 to 27)
- •age >50<80 yrs
- •stable medication for the past 3 months
- •Caucasian ethnicity
排除标准
- •age <50>80 yrs
- •incapability to give informed consent
- •diabetes defined according to American Diabetes Association (ADA) criteria
- •clinically significant liver or kidney dysfunction defined as s-ALT > 2 times upper reference or estimated creatinine-clearance (eGFR) < 60 mL / min/1.73m2, assessed by with CKD-EPI formula
- •endocrinological diseases other than well controlled hypothyroidism, personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia (MEN) syndrome, severe gastro-intestinal diseases (i.e gastroparesis, dumping syndromes), current or history of chronic or acute pancreatitis
- •any contraindication to the use of exenatide as per the Summary of Product Characteristics
- •known abuse of alcohol or drugs
- •ferro-magnetic prosthesis, pacemaker or other metals incorporated in the body
- •significant neurologic disease other than MCI (i.e. Parkinson's disease, multiple system atrophy, normal pressure hydrocephalus, progressive supranuclear palsy, subarachnoid hemorrhage, brain neoplasms, Huntington disease, epilepsy or head trauma)
- •BMI ≤22 Kg/m2 in subject ≥ 70 yrs
- •MRI/CT showing unambiguous etiological evidence of cerebrovascular disease with regard to MCI
- •severe sensory defects; current presence of clinically significant psychiatric disorder
- •warfarin treatment, clinically significant systemic condition
- •history of cancer within the last 5 yrs
- •known allergy to exenatide or any of the other components.
研究组 & 干预措施
placebo
no drug assigned
干预措施: placebo (Other)
exenatide
long-acting exenatide 2 mg subcutaneously once-weekly
干预措施: Exenatide (Drug)
结局指标
主要结局
Improvement of ADAS-cog Alzheimer's Disease Assessment Scale defined by ADAS-cog score at 16 (V2) and at 32 weeks (V3) compared to baseline
时间窗: 16 and 32 weeks
Absolute difference in the ADAS-Cog score compared to baseline in the 2 arms.
次要结局
- Improvement of Mini Mental State Evaluation test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Mini Mental State Evaluation quality test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Phonemic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Semantic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Geriatric Depression Scale (GDS) test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Clinical Dementia Rating Scale (CDR) test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Neuropsychiatric Inventory (NPI) test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Activities of Daily Living (ADL) test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- Improvement of Instrumental Activities of Daily Living (IADL) test at 16 (V2) and at 32 weeks (V3) compared to baseline(16 and 32 weeks)
- changes in structural and functional connectivity of neural networks as assessed by functional MRI (fMRI) at 16 (V2) and at 32 weeks (V3)(16 and 32 weeks)
研究者
Alessandra Dei Cas
Research Assistant, MD, PhD
Azienda Ospedaliero-Universitaria di Parma