Track topics on Twitter Track topics that are important to you
The proposed study is aimed at examining mitochondrial function as a potential target of action of vitamin D on muscle metabolism, size, and strength in preventing the progression of cachexia. This is the first clinical trial designed to understand the effects of vitamin D on muscle metabolic dynamics driving dysfunction in cachectic muscle. Our preliminary data suggest that vitamin D promotes lipid partitioning and muscle metabolic function, which the investigators hypothesize, will mitigate cachexia via improved muscle health and quality that translates into reduced fatigue, and improved patient resilience to multimodal cancer therapy.
Vitamin D repletion is linked to improved muscle mitochondrial function, lipid deposition and preservation; however, while vitamin D insufficiency is common in cancer, the mechanistic effects of vitamin D on muscle metabolic health in cancer patients have not been studied. This is important to address because cancer cachexia is characterized by marked muscle wasting, anabolic resistance, ectopic fat infiltration, mitochondrial dysfunction and contributes to decreased survival. With novel strategies to address this knowledge gap, the investigators will use a combination of advanced metabolic analytical approaches with complementary model systems in cell culture and human subjects to understand the biochemical and physiological mechanisms underlying cancer cachexia in relation to the role of vitamin D in conjunction with resistance exercise (RE). By combining analyses of muscle size and local tissue hemodynamics in vivo, metabolomics analyses of muscle tissue and isolated mitochondria, and changes in anabolic cell signaling, lipid metabolism and oxidative capacity of primary muscle cells in vitro, the investigators will identify mechanisms underlying muscle response to vitamin D repletion. Our previous findings, together with data that exercise improves muscle vitamin D storage and retrieval, suggest that vitamin D repletion synergizes with RE to improve muscle metabolic function and protein synthesis. Our overall objective is to examine mitochondrial function and anabolic resistance as potential targets of action of vitamin D on muscle metabolism, size and strength in preventing the progression of cachexia. The aims of this study are to: 1) non-invasively quantify lipid redistribution, local muscle tissue metabolism and muscle mass and strength of cancer patients before and after 12 weeks of double blinded vitamin D repletion with exercise and protein supplementation (VitD) compared to exercise and protein supplementation only (Ctl); 2) determine differences in muscle mitochondrial function in live tissue biopsied from human gastrocnemius from VitD compared to Ctl; and 3) identify mechanisms whereby vitamin D and exercise regulate muscle anabolic signaling and mitochondrial activity in primary human myotube cultures. Our central hypothesis is that vitamin D promotes muscle lipid availability for β-oxidation in response to exercise, thereby preventing lipotoxicity in the muscle and potentially improving anabolic sensitivity in muscle during cancer cachexia. The impact of this project, the first nutrition and exercise study designed as an inexpensive intervention, is to understand the effect of vitamin D on the metabolic and anabolic dynamics which underpin dysfunction in cachectic muscle. If vitamin D promotes lipid partitioning, muscle metabolic function and/or anabolic sensitivity, these adaptations will ultimately improve cancer therapy by combating cancer cachexia. Further, diffuse optical spectroscopy techniques have the potential to identify the minimum effective intervention dose for optimizing metabolic health leading to more practical and individualized lifestyle prescriptions to reduce health care costs.
Vitamin D, Placebo
Not yet recruiting
University of Kentucky
Published on BioPortfolio: 2017-05-09T13:08:21-0400
Anorexia and cachexia are devastating complications in late-stage cancer patients and is strongly associated with mortality in these patients. Activation of Ghrelin receptors have been de...
Activation of Ghrelin receptors have been demonstrated to stimulate appetite. RC-1291 HCl, by virture of its ghrelin like activity and Growth Hormone releasing effects may have a dual role...
Sarcopenia is an important component of cachexia associated with cancer, and their high incidence in cancer patients emphasizes the need for a better understanding of its mechanisms, which...
SF-C002 is a pilot study in patients with newly diagnosed NSCLC suffering from involuntary weight loss. The study is 12 weeks, double-blinded, placebo controlled and the main objective is ...
The study is designed to evaluate whether daily insulin treatment to weight losing cancer patients attenuates progression of cancer cachexia and improves metabolism.
Cancer cachexia, characterized by weight loss and sarcopenia, leads to a decline in physical function and is associated with poorer survival. Cancer cachexia remains poorly described in older adults w...
Cancer cachexia is associated with poorer outcomes and is often diagnosed by the Fearon criteria. Oncologists clinically identify cachexia based on a patient's presentation. In this study agreement be...
Cachexia is a devastating complication of cancer and an important cause of morbidity and mortality and can have a great effect on quality of life, and sense of self-esteem. Unfortunately; there is no ...
Vitamin D supplementation is often used in the prevention and treatment of osteoporosis, but the role of vitamin D has lately been questioned. We aimed to investigate the effect of 3 months of daily ...
Cancer cachexia is a severe, debilitating condition characterized by progressive body wasting associated with remarkable loss of skeletal muscle weight. It has been reported that cancer cachexia distu...
A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.
A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)
OXIDOREDUCTASES which mediate vitamin K metabolism by converting inactive vitamin K 2,3-epoxide to active vitamin K.
A family of phylloquinones that contains a ring of 2-methyl-1,4-naphthoquinone and an isoprenoid side chain. Members of this group of vitamin K 1 have only one double bond on the proximal isoprene unit. Rich sources of vitamin K 1 include green plants, algae, and photosynthetic bacteria. Vitamin K1 has antihemorrhagic and prothrombogenic activity.
Megestrol acetate is a progestogen with actions and uses similar to those of the progestogens in general. It also has anti-androgenic properties. It is given by mouth in the palliative treatment or as an adjunct to other therapy in endometrial carcinoma and in breast cancer. Megestrol acetate has been approved to treat anorexia and cachexia. (From Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...