INTRAVENOUS IGF-1 INFUSION IN HEAD INJURY

头部损伤时静脉输注 IGF-1

• 批准号: 6112428
• 负责人: Alfred Byron Young
• 金额: $ 13.49万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112428
• 关键词: brain disorder chemotherapy; brain injury; brain metabolism; clinical trials; combination chemotherapy; drug administration rate /duration; excitatory aminoacid; gastrointestinal toxin absorption; head /neck injury; hormone therapy; human subject; human therapy evaluation; insulinlike growth factor; intravenous administration; liver function; longitudinal human study; medical complication; neuroprotectants; neuropsychological tests; somatotropin

Patients with isolated severe head injury must recover from both the primary brain injury and secondary central and peripheral sequelae. Extensive efforts to control elevated intracranial pressure and prevent the systemic complications associated with head injury have improved mortality. Secondary insults, such as metabolic effects, are major contributors to poor outcome. Recent results from basic research and clinical trials demonstrate that damaged nerve cells can regain function. Neurotrophic factors such as insulin-like energy substrates available to the brain, and prevent the detrimental systemic sequelae of brain injury. The metabolic response to brain injury is linked to increased levels of cytokines and catabolic hormones and immunocompetence, altered vascular permeability, and altered gastrointestinal function. Head-injured patients have increased cytokines/catabolic hormones and decreased cytokines/catabolic hormones and decreased IGF-1 may lead to many of the secondary consequences of head injury. Recent studies suggest that providing early adequate nutritional support improves rate of recovery and lessens mortality from head injury. In a preliminary study of 33 patients with severe closed head injury, recombinant IGF-1 was infused for 14 days post-injury at a rate of 0.001 mg/Kg/hr. Favorable trends were observed in treated (IGF-1) versus control groups (saline) for sepsis, rate, nitrogen balance, neurological outcome, and mortality rate. In this clinical project we will study the efficacy of a promising new therapeutic modality, IGF-1 combined with GH. This clinical trial will identify whether or not IGF-1 infusion and subcutaneous GH injection in humans with head injury can significantly whether decrease mortality and improve neurologic outcome. Mechanisms of improvement will also be explored. We hypothesize that intravenous IGF-1 combined with GH may improve outcome of patients with severe head injury through several possible mechanisms: 1) enhanced neural repair or reorganization; 2) altered systemic hyperglycemia and decreased brain lactic acidosis; 3) preservation of normal ratios of amino acid substrates available to brain after injury; 4) decreased infection rate; and 5) decreased gut permeability, cytokine release, and lessened acute-phase and hypercatabolic responses to injury. Basic experiments in project 2,3,4, and 5 will help to identify the mechanisms of the combination IGF-1/GH actions.

患有孤立性严重头部损伤的患者必须从以下两种情况中恢复过来： 原发性脑损伤和继发性中枢和外周后遗症。 广泛努力控制颅内压升高并预防 与头部损伤相关的全身并发症有所改善 死亡。 次要损害，例如代谢影响，是主要的 导致不良结果的因素。 基础研究和最新成果 临床试验表明受损的神经细胞可以恢复功能。 神经营养因子，例如胰岛素样能量底物，可用于 大脑，并防止脑损伤的有害的全身后遗症。 对脑损伤的代谢反应与脑损伤水平升高有关 细胞因子和分解代谢激素和免疫能力，改变血管 通透性和胃肠道功能改变。 头部受伤 患者的细胞因子/分解代谢激素增加，并且减少 细胞因子/分解代谢激素和 IGF-1 减少可能导致许多 头部受伤的次要后果。 最近的研究表明 尽早提供充足的营养支持可提高康复率 并降低头部受伤造成的死亡率。 在一项针对 33 项研究的初步研究中 严重闭合性颅脑损伤患者输注重组IGF-1 受伤后 14 天，剂量为 0.001 毫克/公斤/小时。 有利的趋势 在治疗组（IGF-1）与对照组（盐水）中观察到 败血症、发生率、氮平衡、神经系统结果和死亡率。 在这个临床项目中，我们将研究一种有前途的新药物的功效 治疗方式，IGF-1联合GH。 本次临床试验将 鉴别IGF-1输注和皮下GH注射是否 头部受伤的人是否可以显着降低死亡率 改善神经系统结果。 完善机制也将 探索过。 我们假设静脉注射 IGF-1 联合 GH 可能 通过多种方法改善严重颅脑损伤患者的预后 可能的机制：1）增强神经修复或重组； 2） 改变全身高血糖并减少脑乳酸酸中毒； 3） 保持大脑可用氨基酸底物的正常比例 受伤后； 4）降低感染率； 5）肠道减少 通透性、细胞因子释放以及减少急性期和 对损伤的过度分解反应。 项目2、3、4中的基础实验， 和5将有助于确定IGF-1/GH组合的机制 行动。