Beta-cell Function and Cognition in the Restoring Insulin Secretion (RISE) Study

恢复胰岛素分泌 (RISE) 研究中的 β 细胞功能和认知

• 批准号: 8560429
• 负责人: SUZANNE CRAFT
• 金额: $ 58.13万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8560429
• 关键词: 2,4-thiazolidinedione; Achievement; Address; Adolescent; Adult; Aftercare; Agonist; Alzheimer' s Disease; Amyloid; Ancillary Study; Antidiabetic Drugs; Area; Beta Cell; Biological Markers; Cell physiology; Cells; Child; Childhood; Clinical Research; Cognition; Cognitive; Comorbidity; Dementia; Detection; Diabetes Mellitus; Disease Management; Elderly; Episodic memory; Evaluation; Fasting; Glucose; Human; Hyperglycemia; Impaired cognition; Insulin; Learning; Measurement; Measures; Memory; Metabolic; Metformin; Methods; Mission; Multi-Institutional Clinical Trial; National Institute of Diabetes and Digestive and Kidney Diseases; Neurodegenerative Disorders; Non-Insulin-Dependent Diabetes Mellitus; Occupational; Paired-Associate Learning; Parents; Participant; Patients; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Plasma; Prediabetes syndrome; Prevention; Randomized; Relative (related person); Risk; Rodent; Short-Term Memory; Speed; Staging; Testing; Therapeutic; Thiazolidinediones; Trail Making Test; active method; arm; cognitive change; cognitive function; diabetic; executive function; functional improvement; glargine; glucagon-like peptide; glucose disposal; glucose tolerance; improved; indexing; information processing; insulin secretion; insulin sensitivity; interest; liraglutide; novel strategies; novel therapeutic intervention; primary outcome; public health relevance; receptor; research study; response; secondary outcome; treatment duration; treatment effect; two-arm study

DESCRIPTION (provided by applicant): This application is submitted in response to PAR-12-265 (Ancillary Studies to Major Ongoing Clinical Research Studies to Advance Areas of Scientific Interest within the Mission of the NIDDK). The proposed ancillary study will examine the effects of anti-diabetic treatment on cognitive function and plasma ?-amyloid (a biomarker of cognitive decline related to Alzheimer's disease), in adults and adolescents with prediabetes or early Type 2 Diabetes Mellitus (T2DM) who are participants in the Restoring Insulin Secretion (RISE) Study. We will also examine whether therapeutic modulation of ?-cell function and insulin sensitivity predicts change in cognition and ?-amyloid. The parent adult RISE Study is a placebo-controlled, multi-center, clinical trial in 255 subjects with prediabetes and early T2DM that will address the hypothesis that intensive glucoregulatory control will restore ?-cell functio, and that restorative effects will persist after treatment cessation. Participants will be randomize into 4 treatment arms: placebo, metformin, metformin plus liraglutide, or insulin glargine followed by metformin. Intensive evaluations to assess ?-cell function, insulin sensitivity, and glucose tolerance will occur throughout a 12-month treatment period, followed by 3- and 9-month post-treatment evaluations. A parallel RISE study will be conducted with 90 adolescents who will be randomized to metformin or metformin plus liraglutide. The proposed ancillary study will assess the effects of treatment on cognition and ?-amyloid, and the relationship of endocrinologic changes to changes in cognition, by adding a battery of sensitive measures of memory and psychomotor speed (Continuous Paired Associate Learning Test, One-Card Learning Test, Detection and Identification Test, Trail-Making Test) and plasma ?-amyloid measurement to the RISE studies. We will test the hypotheses that adults in the three active treatment arms will show greater improvement in cognitive scores and lowering of plasma ?-amyloid at 12-months relative to baseline compared with placebo-assigned participants, and that adult and adolescent participants in the metformin plus liraglutide arm will show greater improvement relative to the other active treatment groups. We will also test the hypothesis that changes in insulin secretion (insulin sensitivity-adjusted ?-cell function measures derived from second phase and AIRmax responses) and sensitivity (insulin-adjusted glucose disposal rate) after 12-months of treatment will be related to cognitive and ?-amyloid changes. Finally, we will examine whether cognitive and biomarker changes are maintained after treatment cessation. The ancillary study will address the important questions of whether therapy at early stages of diabetes can improve cognition, and whether improvement is maintained after treatment ends. The study will also examine the relationship of cognitive status with metabolic mechanisms such as impaired insulin secretion and sensitivity that may underlie the increased risk of cognitive decline and neurodegenerative disease associated with prediabetes and T2DM, and thereby suggest novel approaches to treatment and prevention of cognitive decline in patients with these conditions.

描述（由申请人提供）：该申请是针对PAR-12-265（对正在进行的正在进行的临床研究的辅助研究，以促进NIDDK任务内的科学兴趣领域的辅助研究）。提出的辅助研究将研究抗糖尿病治疗对认知功能和血浆？-Amyboid（认知下降的生物标志物与阿尔茨海默氏病有关），对患有糖尿病的成年人和青少年或早期2型2型糖尿病（T2DM）（T2DM）的影响，他们是参与参与的InsuliNSerulion Sertimulion Sertimulion（Recess Insulion Sertimulion（Recals）的Insulion Serivion（Rise）。我们还将检查？细胞功能和胰岛素敏感性的治疗调节是否可以预测认知和淀粉样蛋白的变化。成人成人崛起研究是一项由255名患有糖尿病前和早期T2DM受试者的安慰剂对照，多中心的临床试验，该试验将解决以下假设：密集的葡萄糖控制控制将恢复吗？ - 细胞功能吗？ - 细胞的功能将恢复治疗后的恢复作用。参与者将随机分为4个治疗臂：安慰剂，二甲双胍，二甲双胍加上liraglutide或胰岛素glargine 由二甲双胍。在整个12个月的治疗期间，将进行评估的密集评估，胰岛素敏感性和葡萄糖耐受性，然后进行3个月和9个月的治疗评估。将对90名青少年进行平行的上升研究，这些青少年将被随机分为二甲双胍或二甲双胍加上Liraglutide。拟议的辅助研究将通过添加一系列对记忆和心理速度的敏感度量来评估治疗对认知和淀粉样蛋白的影响，以及内分泌学的变化与认知变化的关系（连续配对的关联学习测试，单卡学习测试，检测测试和识别测试，尾巴测试，跟踪测试，尾巴测试）和质量研究。我们将测试三个主动治疗组中的成年人在认知评分和血浆降低时相对于基线而言，与安慰剂分配的参与者相比，在12个月时的认知评分和降低血浆？ - 淀粉样蛋白的假设，而成人和青少年参与者在二甲甲甲基甲甲基和Liraglutide中的参与者将显示出相对于其他活跃的治疗组的改善。我们还将检验以下假设：胰岛素分泌的变化（胰岛素敏感性调整？ - 源自第二阶段和AIRMAX反应得出的细胞功能度量）和敏感性（胰岛素调整后的葡萄糖处置率），治疗12个月后，治疗方法将与认知能力和？amyloid变化有关。最后，我们将检查治疗停止后是否保持认知和生物标志物的变化。这项辅助研究将解决糖尿病早期治疗是否可以改善认知以及治疗结束后是否保持改善的重要问题。该研究还将研究认知状况与代谢机制的关系，例如胰岛素分泌受损和敏感性受损，这可能是认知下降和神经退行性疾病与糖尿病前期和T2DM相关的神经退行性疾病的增加，因此暗示了这些疾病患者认知能力下降的新方法。