Effects of Liraglutide on Hippocampal Structure and Function in Aging Adults With Prediabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Cognitive Outcomes
研究概览
简要总结
The purpose of this study is to evaluate the effects of liraglutide on the memory and attention of people with insulin resistance. Liraglutide is a medication that makes the body more sensitive to insulin, and therefore may allow it to manage sugar more effectively.
The investigators are looking specifically at a region of the brain that is associated with memory and attention, called the hippocampus, in order to see whether treatment this treatment will change performance on memory and attention tasks. The investigators are also taking an MRI of the brain to see whether there are changes to the size and shape of the hippocampus after treatment.
All subjects in this study will be 50-70 years old and have pre- diabetes. Half of all subjects will have a family history of dementia, while the other half will not.
详细描述
Data from this study will be used to measure changes in hippocampal morphology, functional alterations in the hippocampus during a paired associative memory task, functional connectivity during rest, and neuropsychological performance on hippocampally-mediated cognitive tasks, following double-blind treatment with liraglutide and placebo.
Primary Hypothesis: Subjects receive liraglutide will show significant differences in hippocampal morphology, functional activation and connectivity, and neuropsychological performance, compared to subjects receiving placebo.
Exploratory Aim: To test for potential interactions between modifiable (IR/prediabetes) and non-modifiable (FamHxAD, APOE 4) risk factors with respect to morphological, functional, and neuropshchological changes during double-blind liraglutide treatment.
Study Procedures
The study will be explained to the participant and informed consent obtained. Participant will also be asked whether or not they consent to being videotaped during the study, and if they do, parts of their study participation may be videotaped for staff training purposes. Participants will continue any current psychiatric medication(s) or psychotherapy during the duration of the study (eg. no changes will be made to currently received treatments). Psychiatric Assessment - This will consist of the Mini International Neuropsychiatric Interview(MINI), the 17-item Hamilton Depression Rating Scale (HDRS-17), and the Mini Mental Status Examination (MMSE). The MINI interview takes approximately 20-30 minutes depending on the individual presentation and has screening and skip-out questions that allow for rapid assessment of psychiatric history, current or in remission, to ensure screen-out for psychiatric exclusions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects will be men and women between the ages of 50 and 70 yrs of age, with a BMI of 27 to 37 kg/m2 and at least 12 yrs of education.
- •All subjects will be medically stable (i.e. no uncontrolled or poorly controlled medical illnesses), cognitively-intact as defined by Mini Mental Status Exam (MMSE) score of > 27, and will have adequate visual and auditory acuity to allow for cognitive testing.
- •Metabolic function will be determined as impaired fasting glucose 100-125 mg/dL and/or impaired 2-hr glucose concentration 140-199 and <200mg/dL on 75-g oral glucose challenge.
- •Also, half of all subjects will have a family history of dementia.
排除标准
- •Diagnosis of possible or probable AD, MCI, or any other dementia; evidence of cognitive decline by MMSE score of <27 or self-reported significant decline in memory within the past year (per the Memory Function Questionnaire) (MFQ)
- •History of Type I or Type II diabetes, or fasting plasma glucose > 126 mg/dL
- •History of significant CVD or myocardial infarction; unstable cerebrovascular or pulmonary disease, gallstones, pancreatitis or cancer, multiple endocrine neoplasia (MEN) untreated hypothyroidism, unstable or untreated hypertension, anemia as determined by hematocrit < 30%
- •Abnormal renal clearance as determined by the serum creatinine ³ 1.5 mg/d, hepatic dysfunction as determined by ALT > 2 times the upper limit of normal
- •Presence of medications known to affect insulin action or insulin secretion
- •Premature birth (which may affect MRI findings), history of neurological disorder (ischemic attacks, carotid bruits, or lacunes upon MRI scan), or evidence of neurologic or other physical illness that could produce cognitive deterioration; use of any drug that may significantly affect the OGTT results or cognitive testing results (specifically: cs)
- •Drug or alcohol abuse or dependence within the past 6 months, positive urine toxicology screen for illicit substances at eligibility screening, history of mental illness, with the exception of past mood disorder, or evidence of acute depression as determined by a 17-item Hamilton Depression Rating Scale (HDRS-17) score of 8 or more.
- •Participants with history of mood disorder must be in remission for at least 6 months prior to study entry.
研究组 & 干预措施
Liraglutide
90 days of liraglutide treatment at adjusting dose, up to 1.8mg/day
干预措施: Liraglutide (Drug)
Placebo
90 days of placebo pen, up to 1.8mg/day.
干预措施: Placebo (Drug)
结局指标
主要结局
Cognitive Outcomes
时间窗: Change from Baseline to 3 months
The following battery of tests will take approximately 90 minutes (at both baseline and 12-week follow-up) to complete and will be administered during the afternoon to avoid diurnal effects: Auditory Consonant Trigrams; Benton Visual Retention Test 5th Edition, Boston Naming Test, Buschke-Fuld Selective Reminding Test, Delis Kaplan Executive Function System (DKEFS), Color-Word subtest, DKEFS Tower Test, DKEFS Trail Making Test, DKEFS Verbal Fluency subtest, Purdue Pegboard, Rey-Osterrieth Complex Figure Test, Taylor Complex Figure Task, Wechsler Abbreviated Scale of Intelligence, and the Wechsler Adult Intelligence Scale-3rd Edition.
OGTT
时间窗: Change from Baseline to 3 months
Oral Glucose Tolerance Test (OGTT): After an overnight fast, subjects will be given a oral glucose challenge, wherein plasma glucose concentrations will be measured at baseline, T30min, T60min, T90min, and T120min after 75gm oral glucose load. Individuals with fasting glucose of 100-125 mg/dl and/or a 2-hour glucose of 140-199 mg/dL and less than 200 mg/dL will be eligible for study enrollment. OGTT will be repeated at the end of the study.
次要结局
未报告次要终点
研究者
Natalie Rasgon
Professor
Stanford University