Phase II trial of tesamorelin for cognition in aging HIV-infected persons

替沙莫林对老年艾滋病毒感染者认知功能的 II 期试验

• 批准号: 9276553
• 负责人: RONALD J. ELLIS
• 金额: $ 64.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276553
• 关键词: Address; Adherence; Adipose tissue; Affect; Aging; Attenuated; Behavior Therapy; Behavioral; Biological Markers; Blinded; Brain; Cellular Phone; Central obesity; Cerebrum; Clinical Trials; Cognition; Data; Dementia; Diabetes Mellitus; Diagnostics Research; Dose; Evaluable Disease; Exclusion; Fatigue; Fatty acid glycerol esters; Fostering; Future; Goals; HIV; HIV Seropositivity; HIV-associated neurocognitive disorder; Hepatitis C co-infection; Hippocampus (Brain); Immunologic Markers; Impaired cognition; Impairment; Incentives; Individual; Inflammation; Inflammation Mediators; Insulin-Like Growth Factor I; Intra-abdominal; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Masks; Measures; Medical; Metabolic; Neurites; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurons; Obesity; Outcome; Outcome Study; Participant; Patients; Performance; Persons; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Placebo Control; Placebos; Population; Publishing; Randomized; Research; Risk Factors; Sampling; Scoring Method; Somatomedins; Somatotropin-Releasing Hormone; Source; Testing; Text; Therapeutic; Time; Ursidae Family; Viral; Viral Load result; Visceral; abdominal fat; aged; aging population; analog; angiogenesis; antiretroviral therapy; arm; base; cognitive performance; combat; disability; disability burden; effective therapy; high risk; immune activation; improved; inclusion criteria; inflammatory marker; monocyte; novel; novel strategies; novel therapeutics; open label; phase 2 study; phase 3 study; phase II trial; primary outcome; public health relevance; response; synaptogenesis; therapy duration; tool; virology

 DESCRIPTION: HIV-associated neurocognitive disorders (HAND) affect 30-50% of HIV+ individuals, including those with virologic suppression on combination antiretroviral therapy (cART), and are disproportionately common in older individuals. Neurocognitive impairment in HIV is a source of disability not only in itself, but also because it magnifies impediments due to other HIV-associated non-AIDS (HANA) conditions by interfering with individuals' abilities to effectively implement personal and therapeutic compensatory strategies. Despite this, there is currently no effective treatment. Here we propose to address this need by combining a novel biomedical treatment, tesamorelin, and a state-of-the-art behavioral intervention, 2-way texting, to maximize adherence to study drug. Our preliminary data indicate that abdominal obesity (a marker of visceral adiposity), systemic inflammation, and immune activation are closely linked to HAND. The biomedical treatment will be a randomized, double-masked, placebo-controlled phase II clinical trial of tesamorelin (Tes), a GHRH analogue that reduces visceral adiposity, inflammation and immune activation. Tes has also been shown to increase IGF-1, which promotes brain angiogenesis, neurite outgrowth and synaptogenesis. Inclusion criteria will be HIV+, aged 40-70 years on stable cART for at least 12 weeks with undetectable viral load, with abdominal obesity and potentially reversible HAND. Exclusions will be individuals not meeting criteria for HAND based on published research diagnostic criteria (Antinori et al, 2007) as well as those with diabetes mellitus or hepatitis C coinfection. A total of 140 subjects will be enrolle at UCSD and USC and randomized 3:2 (tesamorelin:placebo) to achieve an evaluable sample of 106 subjects completing treatment for 9 months. We hypothesize that tesamorelin will improve the primary outcome of neurocognitive performance as measured by the global deficit score method. We will also evaluate secondary mechanistic outcomes as follows: 1) biomarkers of inflammation and monocyte activation, 2) brain magnetic resonance spectroscopy (MRS) evidence of cerebral inflammation and 3) MRI hippocampal volume increases. Multiple tools will be used to enhance adherence and combat treatment fatigue in this impaired population, including a state-of-the-art behavioral intervention comprising an adaptation of the individualized Texting for Adherence Building (iTAB) platform. Additional incentives to study participation will be provision of cell phones and data plans for text messaging, an open-label active study drug extension offered to all participants who complete the blinded placebo-controlled phase, and reimbursement for participant time and expense. By optimizing neurocognitive function, we endeavor to reduce the burden of disability in aging HIV-infected individuals on cART. Successful completion of this Phase II trial will lead to larger and longer duration Phase III studies to demonstrate efficacy.

 描述：与HIV相关的神经认知疾病（手）影响30-50％的HIV+个体，包括在抗逆转录病毒疗法（CART）中病毒学抑制的人，并且在老年人中非常普遍。艾滋病毒中的神经认知障碍本身就是一种残疾的根源，而且还因为它通过干扰个人有效实施个人和治疗性补偿策略的能力而放大了由于其他艾滋病毒相关的非AID（HANA）条件而放大了障碍。尽管如此，目前尚无有效的治疗方法。在这里，我们建议通过结合一种新型的生物医学治疗，间谍蛋白和最新的行为干预，即2向发短信，以最大程度地依从性研究药物，以解决这种需求。我们的初步数据表明，腹部肥胖症（内脏肥胖的标记），全身性炎症和免疫激活与手紧密相关。生物医学治疗将是一种随机，双掩盖的安慰剂对照的TESAMORELIL（TES）的II期临床试验，该试验是一种降低内脏肥胖，炎症和免疫激活的GHRH类似物。 TE还显示出增加IGF-1，从而促进脑血管生成，神经落生和突触发生。纳入标准将为HIV+，在稳定的货车上享年40-70岁，至少12周，腹部肥胖症和潜在可逆手，至少为12周。排除将是根据已发表的研究诊断标准（Antinori等，2007）以及糖尿病或丙型肝炎共同感染的人不符合手部标准的人。 UCSD和USC总共将招募140名受试者，并随机分组3：2（Tesamorelin：安慰剂），以获得可评估的106名受试者完成治疗9个月的受试者的样本。我们假设，通过全球赤字评分方法衡量的神经认知性能的主要结果将改善托萨莫林蛋白的主要结果。我们还将评估二级机理结果如下：1）炎症和单核细胞激活的生物标志物，2）脑磁共振光谱（MRS）脑感染的证据和3）MRI海马体积增加。多种工具将用于增强这种受损的人群中的依从性和作战治疗疲劳，包括最先进的行为干预措施，以完成对个性化的改编 依从性建筑（ITAB）平台发短信。研究参与的其他激励措施将是提供手机和文本消息的数据计划，这是为所有完成盲目安慰剂对照阶段的参与者提供的开放标签活跃的研究药物扩展，以及报销参与时间和费用。通过优化神经认知功能，我们努力减少型HIV感染者在购物车中的残疾燃烧。该II期试验的成功完成将导致更长，更长的持续时间III阶段研究以证明效率。