EAA Intake to Optimize Protein Anabolism in COPD

Study Overview
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Brief Summary
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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
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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.

Official Title
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Essential Amino Acid Intake to Optimize Protein Anabolism in Elderly COPD Patients

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Dietary Supplement: Free balanced amino acid mixture
* Dietary Supplement: Free essential amino acid mixture


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COPD patients only<br>Free balanced amino acid mixture or free essential amino acid mixture | Dietary Supplement: Free balanced amino acid mixture<br>* 7 g free amino acids provided as a one time bolus, including 15 g carbohydrates. As part of the total amount of essential amino acids 24% is leucine.<br>* Other names: 7 g AA (24% leucine of the EAA is leucine);Dietary Supplement: Free essential amino acid mixture<br>* 7 g free essential amino acids provided as a one time bolus, including 15 g carbohydrates. As part of the total amount of essential amino acids 40% is leucine.<br>* Other names: 7 g EAA (including 40% leucine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net whole body protein synthesis rate | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole body collagen breakdown rate | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 3 years | 
| Urea turnover rate | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 3 years | 
| Arginine turnover rate | Measured in postabsorptive state | Up to 3 years | 
| Muscle protein breakdown | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 3 years | 
| Amino acid kinetics | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 3 years | 
| Liver protein synthesis rate | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 3 years | 
| Resting Energy expenditure | Measured in postabsorptive state | Up to 3 years | 
| Insulin kinetics | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 3 years | 
| Glucose kinetics | Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement | Up to 3 years | 
| Fat-free mass | Characterization of subjects | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Protein metabolism, Essential amino acid intake