TRH ADMINISTRATION FOR FATIGUE

TRH 疲劳管理

• 批准号: 7607640
• 负责人: ANDREW WINOKUR
• 金额: $ 0.14万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607640
• 关键词: Affect; Analeptics; Animal Model; Antidepressive Agents; Anxiety; Cancer Fatigue; Cancer Patient; Clinical; Cognition; Computer Retrieval of Information on Scientific Projects Database; Cross-Over Studies; Development; Double-Blind Method; Endocrine; Etiology; Fatigue; Functional disorder; Funding; Future; Grant; High Prevalence; Immune; Institution; Intervention; Intravenous; Life; Malignant Neoplasms; Malignant neoplasm of prostate; Motivation; Nootropic Agents; Oral; Patients; Pilot Projects; Placebo Control; Property; Quality of life; Randomized; Research; Research Personnel; Resources; Safety; Source; Symptoms; Therapeutic; Thyrotropin-Releasing Hormone; United States National Institutes of Health; Week; Work; base; cancer therapy; depressive symptoms; hormone analog; malignant breast neoplasm; novel; psychologic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fatigue is the most common and the most debilitating symptom of cancer and cancer treatments. In at least 50% of cancer patients, the etiology of fatigue remains unidentified even after a comprehensive work-up. This idiopathic' cancer fatigue (iCF) is highly prevalent in patients with breast cancer and prostate cancer. Despite its high prevalence and its devastating effect on quality of life, very little evidence exists on pharmacological interventions for treatment of this incapacitating problem affecting the lives of millions of cancer patients. Until we identify the precise mechanisms underlying the pathophysiology of cancer fatigue, it is crucial that we evaluate and develop novel pharmacological interventions targeting the general hypoarousal mechanisms. The analeptic properties of thyrotropin-releasing hormone (TRH) are well established in multiple animal models. Intravenous TRH studies conducted in patients as a cognitive enhancer and an antidepressant, confirmed these analeptic actions of TRH. Patients in these trials showed significant and persistent improvement in energy, motivation, cognition and psychomotor retardation. This novel pilot study proposes a 4-week randomized double blind placebo-controlled cross-over trial to evaluate the efficacy and safety of synthetic thyrotropin-releasing hormone (TRH) to treat cancer-related fatigue in breast cancer and prostate cancer patients. In addition to assessing the impact of TRH administration on fatigue, we will also investigate its impact on patients' depressive and anxiety symptoms, overall psychological status, overall quality of life and global clinical status. We will also investigate the impact of TRH administration on immune and endocrine dysfunction associated with the cancer-related fatigue. This pilot study is a proof-of-principle study and is a vital first step towards the future development of TRH-based therapeutics including oral TRH analogs to treat cancer-related fatigue.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 疲劳是癌症和癌症治疗最常见和最令人衰弱的症状。在至少50%的癌症患者中，即使在全面检查后，疲劳的病因仍然无法确定。这种特发性癌症疲劳（iCF）在乳腺癌和前列腺癌患者中非常普遍。 尽管它的高患病率和对生活质量的破坏性影响，很少有证据表明药物干预治疗这种影响数百万癌症患者生活的失能问题。在我们确定癌症疲劳的病理生理学的确切机制之前，我们评估和开发针对一般低觉醒机制的新的药理学干预措施至关重要。促甲状腺素释放激素（TRH）的催醒特性在多种动物模型中得到了很好的证实。作为认知增强剂和抗抑郁剂在患者中进行的静脉注射TRH研究证实了TRH的这些促醒作用。这些试验中的患者在能量、动机、认知和精神发育迟滞方面表现出显著和持续的改善。这项新的初步研究提出了一项为期4周的随机双盲安慰剂对照交叉试验，以评估合成促甲状腺激素释放激素（TRH）治疗乳腺癌和前列腺癌患者癌症相关性疲乏的疗效和安全性。除了评估TRH给药对疲劳的影响外，我们还将研究其对患者抑郁和焦虑症状、整体心理状态、整体生活质量和全球临床状态的影响。我们还将研究TRH给药对与癌症相关的疲劳相关的免疫和内分泌功能障碍的影响。这项初步研究是一项原理验证研究，是未来开发基于TRH的治疗方法（包括口服TRH类似物）治疗癌症相关疲劳的重要第一步。