TRH ADMINISTRATION FOR FATIGUE

点击翻译按钮获取中文摘要

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.