Memory Advancement by Intranasal Insulin in Type 2 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 289
- 试验地点
- 2
- 主要终点
- Gait Speed Dual-task (cm/s).
研究概览
简要总结
The main purpose of this study is to find the long-term effects of daily administration of 40 IU of intranasal insulin (INI) as compared to placebo (sterile saline) on cognition and memory in people with type 2 diabetes mellitus (DM), and non-diabetic controls over 24 weeks with a follow-up period for 24 weeks. Four groups will be tested: DM group treated with INI; DM group treated with placebo; control group treated with INI and the control group treated with placebo. The INI or placebo will be delivered into the nose. The investigators are interested to see whether INI can improve memory and cognition and blood flow in the brain in the type 2 DM group as compared to placebo and to the non-diabetic group over a long-term period.
详细描述
The investigators propose a randomized controlled trial determining the long-term effects of intranasal insulin (INI) on cognition and memory in type 2 diabetes (DM) and non-DM groups. The investigators hypothesize that: 1) INI-treated adults with DM have better memory and functioning of specific cognitive domains and faster walking during a dual task than those treated with placebo and the control group; 2) Glycemic and insulin resistance and genetic markers for Alzheimer's disease (Apolipoprotein E4 [ApoE4]) may serve as predictors of positive responses to INI therapy; 3) INI treatment neither adversely affects systemic glycemic levels or the cardiovascular system nor causes weight gain.
Aim 1: To determine whether INI-treated type 2 DM adults have a) better memory and functioning of specific cognitive domains and b) faster dual-task gait speed and better daily living functioning than the placebo-treated and non-DM groups. Four groups will be tested: 60 DM subjects treated with insulin; 60 DM subjects treated with placebo; 45 control subjects treated with INI and 45 control subjects treated with placebo. These 210 patients are expected to complete treatment and 168 are expected to complete study by the study completion anticipated date.
The investigators will conduct a randomized, double-blind, placebo-controlled study in 120 older adults with type 2 DM and 90 non-DM controls examining whether 40 IU INI once daily over a 24-week period improves:
- Specific domains of visuospatial attention and memory, verbal learning (primary outcomes);
- Gait speed during a dual task (which is an excellent predictor of overall health), daily living functionality, and depression as compared to the DM group receiving sterile saline and the non-DM groups. The non-DM groups will provide reference of INI effects in a clinical phenotype of cognitive decline and insulin resistance that occurs with normal aging.
Aim 2: To identify a phenotype and long-term trajectory predicting clinically relevant response to INI therapy based on glycemic control, insulin resistance, endothelial and genetic markers.
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)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women aged 50-85 years old
- •Able to walk for 6 minutes
- •Diabetes type 2 (DM) group: diagnosis and treatment for type 2 DM with non-insulin oral or injectable agents
- •Non-DM group with similar age range as the DM group, non-diabetic fasting plasma glucose (<126 mg/dL) and hemoglobin A1c (HbA1c) (<6.5%)
- •Participants capable of providing informed consent
排除标准
- •Type 2 DM treated with insulin (since 9/25/2017)
- •Type 1 DM
- •Intolerance to insulin
- •History of severe hypoglycemia
- •Participants who have >1 asymptomatic and/or symptomatic episode of hypoglycemia (glucose < 54 mg/dL) during finger stick or plasma glucose (cut off value since 6/11/2018)
- •Acute medical condition that required either hospitalization or surgery within the past 6 months (e.g., severe hypoglycemia, malignancies, myocardial infarction,stroke)
- •Liver or renal failure or transplant
- •Dementia (Mini Mental State Examination [MMSE] scores ≤20)
- •Current recreational drug or alcohol abuse
- •Serious systemic disease that would interfere with conduction of clinical trial (mild forms of neurological conditions e.g. Parkinson's Disease, autonomic neuropathy etc. would be allowed)
- •Magnetic Resonance Imaging (MRI) substudy in 40 DM patients only: claustrophobia and implants incompatible with 3-Tesla MRI
- •Safety substudy in 20 IDDM patients only: Insulin-treated type 2 diabetics with a C-peptide of <0.8 ng/mLd and fasting blood glucose >150 mg/dL will be excluded even without history of hypoglycemia during finger stick measurements.
研究组 & 干预措施
Type 2 Diabetes Mellitus - Insulin
40 IU of regular human insulin once daily over 24 weeks
干预措施: Regular Human Insulin (Drug)
Type 2 Diabetes Mellitus - Placebo
Intranasal sterile saline once daily over 24 weeks
干预措施: Placebo (Drug)
Control - Insulin
40 IU of regular human insulin once daily over 24 weeks
干预措施: Regular Human Insulin (Drug)
Control - Placebo
Intranasal sterile saline once daily over 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Gait Speed Dual-task (cm/s).
时间窗: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Gait speed dual-task (cm/s) - walking and counting backwards (subtracting 7) difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Gait Speed Normal Walk (cm/s).
时间窗: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Gait speed normal walk (cm/s) - difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Verbal Memory Composite z Score
时间窗: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Verbal memory composite score was calculated as the sum of Verbal Recognition Memory (VRM) z scores ( 0 indicates the mean; lower score indicates worse outcome). VRM- Free Recall raw score (range 0-12), immediate and delayed VRM-Recognition raw score (range 0-24) were converted to z-scores. Verbal memory composite scores were compared between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Executive Function Composite z Score
时间窗: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
The executive function composite score was calculated as a sum of Paired Associates Learning (PAL) and Spatial Working Memory (SWM) z-scores (range -2 to +2, 0 indicates the mean; higher score indicates worse outcome). Paired Associates Learning - raw score of Total Errors Adjusted (range 0-120) was converted to z-score. Spatial Working Memory - raw score SWM-Between Errors (range 0-42) and raw score of SWM-Strategy (range 8-56) were converted to z-scores. Executive function composite scores were compared between: Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
次要结局
- Weight (kg).(Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).)
- Fasting Plasma Glucose (mg/dL).(Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).)
研究者
Vera Novak
Associate Professor of Neurology
Beth Israel Deaconess Medical Center