Beta Adrenergic Antagonist For The Healing of Chronic Diabetic Foot Ulcers

β 肾上腺素能拮抗剂用于治疗慢性糖尿病足溃疡

• 批准号: 10291797
• 负责人: Sara Dahle
• 金额: --
• 依托单位: VA NORTHERN CALIFORNIA HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10291797
• 关键词: Adrenergic beta-Antagonists; Adverse event; Affect; Amputation; Analysis of Covariance; Analysis of Variance; Animal Model; Basic Science; Blinded; California; Caring; Cells; Characteristics; Chronic; Clinic; Clinical; Clinical Data; Clinical Management; Clinical Research; Clinical Trials Cooperative Group; Colon Carcinoma; Control Groups; Cutaneous; Data; Debridement; Dermatologic; Devices; Diabetes Mellitus; Diabetic Foot Ulcer; Disease; Double-Blind Method; Drainage procedure; Drops; Eligibility Determination; Enrollment; Epithelial; Eyedrops; Foot Ulcer; Functional disorder; Gel; Glaucoma; Health Surveys; Healthcare; Healthcare Systems; Home; Human; Hydrogels; Impaired healing; In Vitro; Individual; Informed Consent; Isopropanol; Knowledge; Laboratories; Laboratory Animals; Laboratory Research; Leg; Logistic Regressions; Lower Extremity; Measurement; Measures; Medical Care Costs; Medicine; Methods; Morbidity - disease rate; Outcome Measure; Patients; Pharmaceutical Preparations; Phase; Placebos; Population; Productivity; Quality of life; Randomized; Randomized Controlled Trials; Recurrence; Reporting; Research; Research Design; Research Personnel; Risk; Safety; Sample Size; Serum; Side; Skin; Sodium Chloride; Sterile coverings; Strawberry nevus; Surface; System; Testing; Therapeutic; Therapeutic Human Experimentation; Time; Timolol; Topical application; Translating; Trauma; Ulcer; United States; United States Department of Veterans Affairs; Veterans; Visit; Wages; Work; angiogenesis; chronic wound; comorbidity Index; cost; diabetic; diabetic patient; diabetic ulcer; early phase clinical trial; follow-up; healing; improved; keratinocyte; lifetime risk; limb amputation; migration; mortality; necrotic tissue; novel strategies; novel therapeutics; pandemic disease; pressure; primary endpoint; psychologic; recidivism; recruit; response; screening; secondary endpoint; secondary outcome; social; standard of care; study population; success; translational study; treatment arm; treatment group; wound; wound care; wound closure; wound healing

Intro: This study will investigate the safety and efficacy of using timolol, a non-selective beta adrenergic antagonist (BAA), topically to treat diabetic foot ulcers. We hypothesize that topical timolol is more effective in achieving wound closure than using the standard of care (SOC) treatment for diabetic foot ulcers, and is a safe therapeutic alternative. Research Design/Methods: The study is a Phase 2 randomized, double blinded, controlled and parallel-group clinical trial with 2 treatment arms, receiving either the SOC plus topical Timoptic-XE® or a control group receiving SOC plus a non biologically active gel (hydrogel, as placebo medicine). The study population will be selected from the VA Northern California Health Care System, Veterans who present with diabetic foot ulcers. We will require 24 subjects enrolled in each treatment arm, for a total of 48 sample size to provide a power of 80% to detect a 43 % difference, with 63% healing in the timolol group and 20% with the standard of care, at a significance level 0.05 and an overall attrition will be 35%. We will perform simple allocation of the subjects using an electronic randomization for treatment assignment. Following recruitment, patients that have met the eligibility criteria and signed an informed consent, will then undergo two weeks of baseline screening to screen out rapid healers. Next, the patient will be randomly assigned treatment, with unique identifiers assigned, with subject and investigator blinded as to treatment. Subjects will topically apply daily either the treatment medication or the placebo on the foot ulcer for 12 weeks, or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a follow-up period. The maximum study duration for any subject is 31 weeks with 3 phases (two weeks in the Screening Phase, up to 12 weeks in the Active Phase including a confirmatory visit, followed by a second confirmatory visit a week later, and one month and three-month in the Follow-Up Phase). Analysis: The primary end point of wound closure (skin re-epithelialization without drainage or dressing requirements) at 12 weeks will be analyzed using the two-sided Fisher's exact test. Secondary outcomes such as the rate of ulcer healing by the 12th week of care, time to achieve complete ulcer closure, recidivism, occurrence of adverse events will be analyzed with p- value adjustments. A two-way ANOVA with a post hoc test will be used to relate timolol serum levels to wound healing. The analysis of the wound characteristics, the subjects' characteristics, and the safety parameters will be performed using logistic regression. Subjects will complete the Veterans Rand (VR-36) Health Survey to evaluate quality of life, the Lower Extremity Functional Scale, which will be analyzed along with the Charlson co-morbidity index, using ANCOVA.

介绍：这项研究将对使用Timolol（一种非选择性β 肾上腺素能的拮抗剂（BAA），局部治疗糖尿病足溃疡。 蒂莫洛（Timolol 治疗糖尿病足溃疡，是一种安全的治疗方法。 研究设计/方法：研究是一项2阶段随机，双盲，受控的 和平行组的临床试验，带有2个治疗臂，接受SOC加上局部试验 Timoptic-XE®或接收SOC的对照组加非生物活性凝胶（水凝胶，AS AS 安慰剂医学）。 研究人群将从VA北加州医疗保健系统中选出 出现糖尿病足溃疡的退伍军人。 治疗臂，总共48个样本量可提供80％的能力来检测43％ 差异，蒂莫洛组的愈合63％，同期为20％，在 显着性水平为0.05，整体损耗将为35％。 我们将使用电子随机化对受试者进行简单分配 招募后的治疗分配，符合符合条件的患者 签署了知情同意书，将接受几周的基线筛选以进行筛选 快速治疗师。 分配了对治疗的主题和研究人员的分配。 每天每天治疗药物或脚溃疡上的安慰剂12周，或直到 治愈，以先到者为准。 将在基线时收集伤口大小和其他数据的测量，然后每周收集 访问12周，然后进行随访期。 31周，有3个阶段（筛选阶段的两个星期，在活动阶段长达12周 包括确认性访问，然后在一周后进行第二次确认访问，一项 在后续阶段和三个月）。 分析：伤口闭合的主要终点（皮肤再上皮无排水 或穿衣要求）在12个Wieks时，使用双面Fisher的精确测试分析。 次要结果，例如在护理的第12周之前的溃疡愈合率，达到的时间 完全关闭溃疡，累犯，不良事件的发生将通过p值分析 调整带有事后测试的双向方差分析 伤口愈合。 安全参数将使用Logistic Lemression执行。 退伍军人兰德（VR-36）健康调查以评估生活质量，下肢 功能量表，将使用Charlson共同点指数一起分析该功能量表 Ancova。