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    Research Grants Awarded

    A pilot study of synthetic thyrotropin-releasing hormone (TRH) administration for the treatment of radiation therapy induced fatigue in breast cancer patients

    Study Section:
    Psycho-Social and Complementary Treatment

    Scientific Abstract:
    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 undergoing adjuvant radiation therapy. 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 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-relaesing 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 patients undergoing radiation therapy. In addition to assessing the impact of TRH administration on fatigue, we will also investigate its impact on patient’s 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.

    Lay Abstract:
    Cancer-related fatigue is the most common symptom reported by cancer patients with a devastating effect on their quality of life and their ability to sustain usual and desired personal, professional, and social relationships. It reduces patients’ participation in leisure activities; ability to work and capacity to sustain meaningful relationships with loved ones. It is observed at a very high rate in breast cancer patients undergoing radiation therapy. These patients suffer silently as we know very little about the causes of this fatigue and know almost nothing about its treatment. At present, effective evidence-based therapies to treat this distressing symptom are almost non-existent. Thyrotropin-releasing hormone (TRH) is a hormone produced in the central nervous system. Over the past few years, TRH related research has shown that actions of TRH extend far beyond its known role as a hormone in the thyroid axis. Significant positive improvement in fatigue, energy level, motivation and vigor was seen when TRH was given to patients with depression and to patients with cognitive difficulties simultaneously suffering from fatigue. These stimulating properties of TRH may be useful in treating radiation therapy induced fatigue in breast cancer patients. This proposed study attempts to systematically investigate if TRH can be a safe and effective agent for the treatment of radiation therapy induced fatigue in breast cancer patients. In this 4-week study, breast cancer patients suffering from radiation therapy induced fatigue will receive TRH and placebo (normal saline) at different time points. Questionnaires will be used to measure fatigue level, depressive and anxiety symptoms, overall emotional status and quality of life. Selected physiological markers will be investigated in an attempt to detect unidentified mechanisms of cancer-related fatigue. There is a pressing need to develop novel treatment strategies to treat cancer-related fatigue as very little evidence exists on effective therapies to treat this debilitating problem. This proposed proof-of-principle study will provide us with critical preliminary information on TRH systems as a potentially novel strategy to treat this devastating problem affecting lives of millions of cancer patients.