Essential Amino Acid Intake to Optimize Protein Anabolism in Elderly Chronic Obstructive Pulmonary Disorder (COPD) Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Marielle PKJ Engelen, PhD, Texas A&M University
ClinicalTrials.gov Identifier:
NCT01173354
First received: July 29, 2010
Last updated: June 12, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Chronic Obstructive Pulmonary Disease
Dietary Supplement: Essential amino acid intake + Leucine vs total AA supplement

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Essential Amino Acid Intake to Optimize Protein Anabolism in Elderly COPD Patients

Resource links provided by NLM:


Further study details as provided by Texas A&M University:

Primary Outcome Measures:
  • Net whole body protein synthesis rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement


Secondary Outcome Measures:
  • Whole body collagen breakdown rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

  • Urea turnover rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

  • Arginine turnover rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Measured in postabsorptive state

  • Muscle protein breakdown [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

  • Amino acid kinetics [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

  • Liver protein synthesis rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

  • Resting Energy expenditure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Measured in postabsorptive state

  • Insulin kinetics [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

  • Glucose kinetics [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

  • Fat-free mass [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Characterization of subjects


Estimated Enrollment: 34
Study Start Date: January 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral EAA vs. total AA supplement Dietary Supplement: Essential amino acid intake + Leucine vs total AA supplement
7 g as bolus
Other Name: 7 g EAA + 40% LEU

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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of chronic airflow limitation, defined as measured forced expiratory volume in one second (FEV1) less than 70% of referen¬ce 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01173354

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
Texas A&M University
Investigators
Principal Investigator: Marielle PK Engelen, PhD University of Arkansas
  More Information

No publications provided

Responsible Party: Marielle PKJ Engelen, PhD, PhD, Texas A&M University
ClinicalTrials.gov Identifier: NCT01173354     History of Changes
Other Study ID Numbers: 105558
Study First Received: July 29, 2010
Last Updated: June 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Texas A&M University:
COPD
Protein metabolism
Essential amino acid intake

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 14, 2014