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

基本信息

批准号：
10683725
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
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10683725
关键词：
Adrenergic beta-Antagonists Adverse event Affect Amputation Analysis of Covariance Analysis of Variance Animal Model Animals 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 Electronics Eligibility Determination Enrollment Epithelium 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 Research Leg Logistic Regressions Lower Extremity Measurement Measures Medical Care Costs Medicine Methods Morbidity - disease rate Outcome Measure Patients Persons 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 Research Time Timolol Topical application Translating Trauma Ulcer United States United States Department of Veterans Affairs Veterans Visit Wages Work angiogenesis body system chronic wound clinical translation 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

项目摘要

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.

简介：本研究将调查使用噻吗洛尔（一种非选择性β）的安全性和有效性肾上腺素能拮抗剂（BAA），局部治疗糖尿病足溃疡。噻吗洛尔在实现伤口闭合方面比使用标准护理 (SOC) 更有效治疗糖尿病足溃疡，是一种安全的治疗选择。研究设计/方法：该研究是一项随机、双盲、对照的 2 期研究以及 2 个治疗组的平行组临床试验，接受 SOC 加局部治疗 Timoptic-XE® 或对照组接受 SOC 加非生物活性凝胶（水凝胶，如安慰剂药物）。研究人群将从 VA 北加州医疗保健系统中选出，患有糖尿病足溃疡的退伍军人每个项目都需要 24 名受试者。治疗臂，总共 48 个样本量，提供 80% 的功效，检测到 43% 差异，噻吗洛尔组的治愈率为 63%，而标准护理组的治愈率为 20%。显着性水平为 0.05，总体流失率为 35%。我们将使用电子随机化对受试者进行简单分配招募后，符合资格标准的患者和签署知情同意书，然后将进行两周的基线筛查以筛选出接下来，患者将被随机分配治疗，并具有唯一的标识符。分配，受试者和研究者对治疗不知情。每天使用治疗药物或安慰剂治疗足部溃疡，持续 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结果，然后每周收集一次为期 12 周的访问，然后是随访期任何科目的最长研究持续时间为 31 周，分 3 个阶段（筛选阶段两周，活跃阶段长达 12 周）包括一次确认性访视，一周后进行第二次确认性访视，以及一次一个月和后续阶段的三个月）。分析：主要终点伤口闭合（皮肤再上皮化，无需引流或着装要求）在 12 周时将使用两侧 Fisher 精确检验进行分析。次要结果，例如护理第 12 周时的溃疡愈合率、达到目标的时间溃疡完全闭合、累犯、不良事件发生情况将用p值进行分析将使用事后检验的双向方差分析来关联噻吗洛尔血清水平。伤口愈合的分析。安全参数将使用逻辑回归进行。受试者将完成。退伍军人兰德 (VR-36) 健康调查，评估下肢生活质量功能量表，将与查尔森合并症指数一起分析，使用方差分析。