Hydrolyzed Casein and Whey Protein Supplementation and the Addition of Leucine to Induce Protein Anabolism in Malnourished COPD Patients
The aim of this study is the first aim of a NIH project that consists of 3 aims. The first aim examines the acute effects of two high-quality milk proteins (casein vs. whey) on whole-body and muscle protein metabolism in COPD patients with severe loss of muscle mass and the effects of adding leucine. The principal endpoints will be the extent of stimulation of net whole body protein synthesis as this is the principal mechanism by which either amino acid or protein intake causes muscle anabolism. After determining the optimal nutritional formulation based on the first aim we will continue to work on the second and third aim where fish oil supplementation will be part of the nutritional intervention as well.
Cachectic COPD patients are characterized by a decreased muscle protein synthesis and an elevated myofibrillar protein breakdown. A substantial number of these patients, characterized by an enhanced systemic inflammatory response, fails to respond to nutritional therapy, which is of clinical relevance as weight gain to nutritional therapy is a significant, independent predictor of mortality in COPD.
In the present study, the acute protein anabolic effect of two high-quality milk protein supplements in COPD will be examined by comparing a hydrolyzed casein and whey protein meal. We make use of hydrolyzed proteins to correct for absorption differences. Furthermore the effects of these milk proteins with or without enrichment of leucine will be investigated.
Variables of interest are: net whole body protein synthesis; whole body protein synthesis and breakdown rate; whole body myofibrillar protein breakdown rate; whole body collagen breakdown; kinetics of insulin; glucose; amino acid levels.
It is the investigators hypothesis that a nutritional supplement containing casein protein and high levels of leucine will target the metabolic alterations of these cachectic COPD patients and will specifically stimulate protein anabolism. The knowledge gained from this study will benefit our insight in terms of promotion of protein anabolism in COPD patients. The long-term goal is to reformulate nutritional composition in accord with the effects of COPD on protein metabolism in order to ameliorate or even prevent progressive muscle wasting in these subjects, and improve their quality of life and survival rates.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)
Chronic Obstructive Pulmonary Disease
Casein protein hydrolysates, Whey protein hydrolysates, Casein protein hydrolysates + LEU, Whey protein hydrolysates + LEU
University of Arkansas for Medical Sciences
Texas A&M University
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT01154400
- Information obtained from ClinicalTrials.gov on November 08, 2012
Medical and Biotech [MESH] Definitions
Casein Kinase I
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kD. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
Casein Kinase Ialpha
A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the CELL CYCLE, membrane trafficking, and RNA processing. In DROSOPHILA casein kinase Ialpha has been in regulation of Hedghog and Wingless signaling pathways. Multiple isoforms of casein kinase Ialpha exist and are due ALTERNATIVE SPLICING.
Casein Kinase Ii
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
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