EAA Intake to Optimize Protein Anabolism in COPD

NCT01173354 | Completed

• 1 other identifier: 105558
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Protein metabolism; Essential amino acid intake

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Whole body collagen breakdown rate

  Up to 3 years

• Urea turnover rate

  Up to 3 years

• Arginine turnover rate

  Up to 3 years

• Muscle protein breakdown

  Up to 3 years

• Amino acid kinetics

  Up to 3 years

Study Arms (1)

COPD patients only

EXPERIMENTAL

Free balanced amino acid mixture or free essential amino acid mixture

Dietary Supplement: Free balanced amino acid mixture; Dietary Supplement: Free essential amino acid mixture

Interventions

Free balanced amino acid mixture DIETARY_SUPPLEMENT

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.

Also known as: 7 g AA (24% leucine of the EAA is leucine)

COPD patients only

Free essential amino acid mixture DIETARY_SUPPLEMENT

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.

Also known as: 7 g EAA (including 40% leucine)

COPD patients only

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Texas A&M University: lead

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (2)

• Engelen MPKJ, Kirschner SK, Coyle KS, Argyelan D, Neal G, Dasarathy S, Deutz NEP. Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease. Clin Nutr. 2023 Sep;42(9):1737-1746. doi: 10.1016/j.clnu.2023.06.031. Epub 2023 Jul 26.

  PMID: 37542951 DERIVED

• Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease. Am J Clin Nutr. 2016 Jun;103(6):1458-64. doi: 10.3945/ajcn.115.125187. Epub 2016 May 4.

  PMID: 27146652 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Excitatory Amino Acids; Leucine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Branched-Chain; Amino Acids, Essential

Study Officials

• Marielle PK Engelen, PhD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: July 29, 2010
• First Posted: August 2, 2010
• Study Start: September 8, 2009
• Primary Completion: February 17, 2012
• Study Completion: February 17, 2012
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

US (1)