Utilizing an RCT Approach to Compare the Efficacy and Sustainability of Technological and Psycho-Educational Interventions to Improve Impaired Awareness of Hypoglycemia in Type 1 Diabetes.

利用 RCT 方法比较技术和心理教育干预措施的有效性和可持续性，以改善 1 型糖尿病患者低血糖的意识受损。

• 批准号: 10598699
• 负责人: Simon Richard Heller
• 金额: $ 25.17万
• 依托单位: UNIVERSITY OF SHEFFIELD
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-25 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598699
• 关键词: Address; Adrenal Glands; Adult; Affect; Age; Anxiety; Attitude; Awareness; Behavior; Blood Glucose; C-Peptide; Cardiovascular Diseases; Characteristics; Clinical; Clinical Trials; Closure by clamp; Cognitive; Complications of Diabetes Mellitus; Data; Diabetes Mellitus; Education; Educational Intervention; Elderly; Enrollment; Epinephrine; Exhibits; Fright; Glucose; Glucose Clamp; Glycosylated hemoglobin A; Heterogeneity; Hormones; Hybrids; Hyperglycemia; Hypoglycemia; Impairment; Incidence; Individual; Insulin-Dependent Diabetes Mellitus; Intervention; Intervention Studies; Intervention Trial; Lead; Measures; Mental Depression; Modernization; Outcome Measure; Participant; Pathway interactions; Patient Outcomes Assessments; Patient Self-Report; Peripheral Nervous System Diseases; Persons; Population; Pump; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recovery; Recurrence; Reporting; Research; Running; Safety; Scientist; Self Care; Symptoms; Technology; Therapeutic Intervention; Time; Training; Work; aged; arm; autonomic neuropathy; comparative efficacy; compare effectiveness; diabetes distress; effective intervention; effective therapy; evidence base; follow-up; glucose monitor; high risk; human very old age (85+); improved; insight; primary outcome; programs; psychoeducational; psychoeducational intervention; recruit; response; restoration; secondary outcome; success; targeted treatment; therapeutically effective; therapy design; treatment arm; two-arm study

Abstract Impaired awareness of hypoglycemia (IAH) remains a major issue in type 1 diabetes (T1D) affecting ~30% of all adults with T1D who are at high risk of severe hypoglycemia. Interventions including hybrid closed-loop (HCL) and education have been developed, which reduce time in hypoglycemia in the hope that IAH will be reversed. All have shown benefit, but many individuals do not respond. Our objective is to identify the most effective treatments according to specific clinical characteristics. We will run two multi-center, unblinded, two-arm, parallel-group randomized controlled trials (RCTs) over 12 months with a 2-4 week run-in (with continued follow-up for 24 months). Our trial interventions are, HCL, blood glucose awareness training (BGAT), Recovery of Hypoglycemia Awareness in Long- Standing Type 1 Diabetes ‘HypoCOMPaSS’ and Hypoglycemia Awareness Restoration Program for adults with type 1 diabetes and problematic hypoglycemia despite optimized self-care ‘HARPdoc’. We will assess the impact of these interventions on restoration of impaired sympatho-adrenal responses to experimental hypoglycemia and restoration of clinical hypoglycemia awareness in T1D. Trial 1 is an RCT in those with IAH, HCL naïve, in two treatment arms (HCL vs. BGAT). At 6 months, the BGAT group will be provided with HCL, both groups then followed-up at 12 & 24 months. Trial 2 is an RCT in IAH persisting despite using HCL for at least 6 months with randomization to HypoCOMPaSS or BGAT for 6 months. At 6 months, those with restored awareness will continue in both arms for a further 6 months and then assessed at 12 & 24 months. Participants with persistent IAH at 6 months will enter an exploratory study and receive HARPdoc for 6 months with assessments at 12 & 24 months. Trials 1 and 2 will recruit in total at least 1000 participants across 10 centers, aged 18 to 85 years old, T1D >1 year duration with IAH, including 10-15% of older adults (³70 years and/or with cardiovascular disease) who will be randomized to all interventions excluding glucose clamps and will be assessed for IAH by questionnaires. The primary outcome is epinephrine response at a clamped glucose of 45 mg/dL comparing the two study arms in both trials at 6 months post-randomization. Secondary outcomes (at baseline, 6, 12 and 24 months) include additional counter-regulatory hormone responses, continuous glucose monitoring (CGM) metrics, C- peptide, HbA1c, patient reported outcome measures (PROMs) including IAH scales, severe hypoglycemia and safety data. All participants will measure CGM metrics, IAH by questionnaire, and report hypoglycemia, PROMs and other data over 2 years to measure ‘real world’ sustainability but will not repeat hypoglycemic clamps at 24 months unless other measures of IAH prove unreliable in reflecting impaired epinephrine responses at 12 months. Overall, these studies will enable future research in developing specific interventions for IAH and lead to more effective therapeutic pathways.

抽象的 在影响〜30％的1型糖尿病（T1D）中，低血糖（IAH）的认识受损仍然是一个主要问题 在患有严重低血糖症的高风险的所有患有T1D的成年人中。包括混合闭环在内的干预措施 （HCL）和教育已经开发出来，这减少了低血糖的时间，希望IAH会成为 逆转。所有人都表现出好处，但许多人没有回应。我们的目标是确定最大的 根据特定的临床特征有效治疗。 我们将运行两个多中心，未盲的双臂平行组随机对照试验（RCT） 超过12个月的时间为2-4周（持续24个月）。我们的审判干预措施是 HCL，血糖意识训练（BGAT），长血糖意识的恢复 站立1型糖尿病的糖尿病和低血糖意识恢复计划 患有1型糖尿病的成年人和有问题的低血糖所需的优化自我保健“ HARPDOC”。 我们将评估这些干预措施对恢复受损的交感神经反应的影响 T1D中临床低血糖意识的实验性低血糖和恢复。试验1是RCT 患有IAH，HCl的人在两个治疗组中（HCL与BGAT）。在6个月时，BGAT组将 然后提供HCL，然后在12和24个月后进行跟进。试验2是IAH持续存在的RCT 尽管使用HCL至少6个月，将随机化与hypocompass或BGAT 6个月。在6 几个月，那些恢复意识的人将在双臂上继续持续6个月，然后在 12和24个月。 6个月时IAH持续存在的参与者将进入探索性研究并接受 HARPDOC持续6个月，在12和24个月时进行评估。试验1和2将总共招募至少1000 跨10个中心的参与者，年龄18至85岁，T1D> 1年的IAH持续时间，其中包括10-15％ 老年人（六年70岁和/或患有心血管疾病），他们将被随机分为所有干预措施 不包括葡萄糖夹，并将通过问卷调查对IAH进行评估。 主要结果是在45 mg/dl的夹紧葡萄糖下进行肾上腺素反应，比较了这两个研究 随机化后6个月的两个试验中的武器。次要结果（基线，6、12和24个月） 包括其他反调节激素反应，连续葡萄糖监测（CGM）指标，C- 胡椒粉，HBA1C，患者报告了结果指标（PROM），包括IAH量表，严重低血糖症和 安全数据。所有参与者将通过问卷调查测量CGM指标，并报告低血糖， 舞会和其他2年的数据来衡量“现实世界”可持续性，但不会重复降低血糖 除非其他IAH的措施证明反映肾上腺素受损不可靠，否则在24个月时夹具 回答12个月。总体而言，这些研究将使未来的研究在制定特定干预措施中 对于IAH并导致更有效的治疗途径。