Vitamin D for Muscle Metabolic Function in Cancer Cachexia
Condition: Cancer Cachexia; Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency; Wasting Syndrome; Cachexia
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Vitamin D; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 5,000IU vitamin D given daily for 12 weeks; Placebo capsules given daily for 12 weeks
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective, double-blinded randomized controlled clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: vitamin D; muscle; metabolism; cancer cachexia