TRH ADMINISTRATION FOR FATIGUE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 疲劳是癌症和癌症治疗中最常见也是最令人虚弱的症状。在至少50%的癌症患者中，即使在进行了全面的检查后，疲劳的原因仍未确定。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。尽管它的高患病率及其对生活质量的破坏性影响，但很少有证据表明，通过药物干预来治疗这一影响数百万癌症患者生活的丧失能力的问题。在我们确定癌症疲劳的确切病理生理学机制之前，评估和开发针对一般低觉醒机制的新的药物干预是至关重要的。促甲状腺激素释放激素(TRH)的催眠特性在多种动物模型中得到了很好的证实。在患者身上进行的静脉注射TRH作为认知增强剂和抗抑郁剂的研究证实了TRH的这些苏醒作用。这些试验中的患者在精力、动机、认知和精神运动发育迟缓方面显示出显著和持续的改善。这项新的先导性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劳的有效性和安全性。除了评估TRH对疲劳的影响外，我们还将调查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况的影响。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。这项先导性研究是一项原则验证研究，是未来发展基于TRH的疗法的重要第一步，包括口服TRH类似物来治疗癌症相关的疲劳。

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.