Leucine-enriched Essential Amino Acid Intake to Optimize Protein Anabolism in Children With Cystic Fibrosis

This study has been completed.
Sponsor:
Collaborator:
Arkansas Children's Hospital Research Institute
Information provided by (Responsible Party):
Marielle PKJ Engelen, PhD, Texas A&M University
ClinicalTrials.gov Identifier:
NCT01172301
First received: July 27, 2010
Last updated: June 12, 2013
Last verified: June 2013
  Purpose

Malnutrition, including muscle wasting commonly occurs in children with cystic fibrosis (CF), negatively influencing their quality of life and survival. At the time of a diagnosis of CF, severe protein deficits can already be present. It is important to get CF children fed adequately to prevent that their condition becomes worse or that recovery takes longer. Oral supplementation trials showed that gains in lean body mass are difficult to achieve in CF unless specific metabolic abnormalities are targeted. However, the specific needs for certain food components are not clear yet in children that are ill. Therefore, more information is necessary on the need for protein and certain amino acids in children with CF. 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 CF.

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 pediatric subjects with CF. In the present proposal, the acute metabolic effects of this high leucine essential amino acids mixture will be examined in pediatric subjects with CF and compared to that of a regular balanced total mixture of essential and non-essential 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
Cystic Fibrosis
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: Leucine-enriched Essential Amino Acid Intake to Optimize Protein Anabolism in Children With Cystic Fibrosis

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 2 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 2 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 2 years ] [ Designated as safety issue: No ]
    Measured in postabsorptive state

  • Liver 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

  • Resting Energy expenditure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Measured in postabsorptive state

  • Insulin kinetics [ 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

  • Amino acid kinetics [ 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

  • Glucose kinetics [ 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

  • Fat-free mass [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Characterization of subjects


Enrollment: 14
Study Start Date: July 2008
Study Completion Date: February 2013
Primary Completion Date: December 2012 (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, we will test the following hypothesis: A high-leucine essential amino acid mixture (dose of 6.7 g) will stimulate protein anabolism to a greater extent than a standard balanced mixture of total (essential and non-essential) amino acids in CF pediatric subjects. 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 pediatric subjects with CF.

  Eligibility

Ages Eligible for Study:   10 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects who already have a diagnosis of CF based on universal diagnostic criteria.
  2. Age 14 to 21 years at the time of enrollment
  3. Under routine medical control at the CF center of ACH
  4. Admitted to the ACH for treatment of pulmonary exacerbation of CF disease.
  5. Improvement in lung function (FEV1) at the time of enrollment back to baseline values (as determined in the clinically stable pre-hospital period)
  6. Central or peripheral venous line in place
  7. No planned major changes or interventions in the treatment and care of the pediatric subject on Day -2 and -1 before discharge from the hospital.

Exclusion Criteria:

  1. Established diagnosis of Diabetes Mellitus
  2. Presence of fever within the last 3 days
  3. Unstable metabolic diseases including liver (cirrhosis) or renal disease
  4. Chronic respiratory failure with cor pulmonale
  5. Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment
  6. Any other condition according to the principle investigator or study physician would interfere with collecting study samples
  7. Failure to give assent / informed consent
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01172301

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
Texas A&M University
Arkansas Children's Hospital Research Institute
Investigators
Principal Investigator: Nicolaas EP Deutz, MD, PhD University of Arkansas
  More Information

No publications provided

Responsible Party: Marielle PKJ Engelen, PhD, PhD, Texas A&M University
ClinicalTrials.gov Identifier: NCT01172301     History of Changes
Other Study ID Numbers: 104738
Study First Received: July 27, 2010
Last Updated: June 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Texas A&M University:
CF
protein metabolism
essential amino acid intake

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 20, 2014