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 低血糖意识受损 (IAH) 仍然是 1 型糖尿病 (T1D) 的一个主要问题，影响约 30% 患有严重低血糖的所有 T1D 成人患者中。干预措施包括混合闭环 （HCL）和教育已经发展起来，减少了低血糖的时间，希望 IAH 能够 颠倒了。所有人都显示出益处，但许多人没有做出反应。我们的目标是找出最 根据具体的临床特点进行有效的治疗。 我们将开展两项多中心、非盲法、双臂、平行组随机对照试验 (RCT) 超过 12 个月，其中有 2-4 周的磨合期（持续随访 24 个月）。我们的试验干预措施是， HCL、血糖意识培训（BGAT）、长期低血糖意识的恢复 站立 1 型糖尿病“HypoCOMPaSS”和低血糖意识恢复计划 尽管有优化的自我护理“HARPdoc”，但仍患有 1 型糖尿病和低血糖问题的成年人。 我们将评估这些干预措施对恢复受损的交感肾上腺反应的影响 T1D 实验性低血糖和临床低血糖意识的恢复。试验 1 是一项随机对照试验 患有 IAH、未接受过 HCL 治疗的患者，分为两个治疗组（HCL 与 BGAT）。 6 个月时，BGAT 组将 两组均提供 HCL，然后在 12 个月和 24 个月时进行随访。试验 2 是 IAH 持续的随机对照试验 尽管使用 HCL 至少 6 个月，并随机分配至 HypoCOMPaSS 或 BGAT 6 个月。 6点 个月，恢复意识的人将继续双臂保持 6 个月，然后进行评估 12 和 24 个月。 6 个月时患有持续性 IAH 的参与者将进入一项探索性研究并接受 HARPdoc 为期 6 个月，并在 12 和 24 个月时进行评估。试验1和2总共将招募至少1000名 10 个中心的参与者，年龄 18 至 85 岁，T1D 患有 IAH 持续时间 > 1 年，其中 10-15% 将随机接受所有干预措施的老年人（³70 岁和/或患有心血管疾病） 不包括葡萄糖钳夹，并将通过问卷调查评估 IAH。 主要结局是比较两项研究时钳制葡萄糖为 45 mg/dL 时的肾上腺素反应 随机化后 6 个月时，在两项试验中进行分组。次要结局（基线、6、12 和 24 个月） 包括额外的反调节激素反应、连续血糖监测 (CGM) 指标、C- 肽、HbA1c、患者报告结果测量 (PROM)，包括 IAH 量表、严重低血糖和 安全数据。所有参与者将通过问卷测量 CGM 指标、IAH，并报告低血糖情况， PROM 和其他超过 2 年的数据可衡量“现实世界”的可持续性，但不会重复低血糖 除非 IAH 的其他测量方法证明反映肾上腺素受损不可靠，否则在 24 个月时进行钳制 12个月时的反应。总体而言，这些研究将使未来的研究能够制定具体的干预措施 IAH 并导致更有效的治疗途径。