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EAA Intake to Optimize Protein Anabolism in COPD

Not Applicable
Conditions
Chronic Obstructive Pulmonary Disease
Interventions
Dietary Supplement: Free balanced amino acid mixture
Dietary Supplement: Free essential amino acid mixture
Registration Number
NCT01173354
Lead Sponsor
Texas A&M University
Brief Summary

Weight loss commonly occurs in patients with chronic obstructive pulmonary disease (COPD), negatively influencing their quality of life, treatment response and survival. Loss of muscle protein is generally a central component of weight loss in COPD patients. Attempts to reverse muscle loss in COPD by supplying large amounts of protein or calories to these patients have been unsuccessful. Gains in muscle mass are difficult to achieve in COPD unless specific metabolic abnormalities are targeted. The investigators recently observed that alterations in protein metabolism are present in normal weight COPD patients. Elevated levels of protein synthesis and breakdown rates were found in this COPD group indicating that alterations are already present before muscle wasting occurs. Furthermore, reduced plasma essential amino acid (EAA) levels were observed in COPD patients. These reduced EAA plasma levels were significantly related with the presence of muscle wasting in COPD. Until now, limited research has been done examining protein metabolism and the response to feeding in patients with COPD. Previous studies support the concept of essential amino acids (EAA) as an anabolic stimulus in the young and elderly and in insulin resistant states. Until yet no information is present on the anabolic effects of EAA in elderly COPD patients.

It is therefore our hypothesis that a high-leucine essential amino acids mixture specifically designed to stimulate protein anabolism will target the metabolic alterations of COPD patients. In the present study, the acute effects of an EAA nutritional supplement on whole body, muscle and liver protein metabolism will be examined in COPD patients and compared to a supplement consisting of a balanced mixture of total amino acids. The principal endpoints will be the extent of stimulation of whole body protein synthesis as this is the principal mechanism by which either amino acid or protein intake causes muscle anabolism, and the reduction in endogenous protein breakdown. Both endpoints will be assessed by isotope methodology which is thought to be the reference method.

Detailed Description

In this study the investigators will test the following hypothesis: A high-leucine essential amino acid mixture (dose of 7.0 g EAA + 15 g carbohydrates) will stimulate protein anabolism to a greater extent than a standard balanced mixture of total (essential and non-essential) amino acids (dose of 6.7 g total AA + 15 g carbohydrates) in COPD patients. The principal endpoints will be the extent of stimulation of protein synthesis rate and the reduction in endogenous protein breakdown. The current project will provide information that will enable us to better understand the underlying metabolic mechanisms that regulate protein metabolism in patients with COPD.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
34
Inclusion Criteria
  • Diagnosis of chronic airflow limitation, defined as measured forced expiratory volume in one second (FEV1) less than 70% of reference FEV1
  • Shortness of breath on exertion
  • Age 45 years and older
  • Clinically stable condition and not suffering from respiratory tract infection or exacerbation of their disease (defined as a combination of increased cough, sputum purulence, shortness of breath, systemic symptoms such as fever, and a decrease in FEV1 > 10% compared with values when clinically stable in the preceding year) at least 4 weeks prior to the study
  • Ability to lie in supine position for 6 hours
Exclusion Criteria
  • Established diagnosis of malignancy
  • Presence of fever within the last 3 days
  • Established diagnosis of Diabetes Mellitus
  • Untreated metabolic diseases including hepatic or renal disorder
  • Presence of acute illness or metabolically unstable chronic illness
  • Recent myocardial infarction (less than 1 year)
  • Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment
  • Any other condition according to the PI or study physicians would interfere with proper conduct of the study / safety of the patient
  • Failure to give informed consent

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
COPD patients onlyFree essential amino acid mixtureFree balanced amino acid mixture or free essential amino acid mixture
COPD patients onlyFree balanced amino acid mixtureFree balanced amino acid mixture or free essential amino acid mixture
Primary Outcome Measures
NameTimeMethod
Net whole body protein synthesis rateUp to 2 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Secondary Outcome Measures
NameTimeMethod
Fat-free massUp to 3 years

Characterization of subjects

Whole body collagen breakdown rateUp to 3 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Arginine turnover rateUp to 3 years

Measured in postabsorptive state

Liver protein synthesis rateUp to 3 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Urea turnover rateUp to 3 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Muscle protein breakdownUp to 3 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Amino acid kineticsUp to 3 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Insulin kineticsUp to 3 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Resting Energy expenditureUp to 3 years

Measured in postabsorptive state

Glucose kineticsUp to 3 years

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Trial Locations

Locations (1)

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

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