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

NCT01172301 | Completed

• 1 other identifier: 104738
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cystic Fibrosis

Keywords

CF; 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 (9)

• Whole body collagen breakdown rate

  Up to 2 years

• Urea turnover rate

  Up to 2 years

• Arginine turnover rate

  Up to 2 years

• Liver protein synthesis rate

  Up to 2 years

• Resting Energy expenditure

  Up to 2 years

Study Arms (1)

Oral EAA vs total AA supplement

EXPERIMENTAL

Dietary Supplement: Essential amino acid intake + Leucine vs total AA supplement

Interventions

Essential amino acid intake + Leucine vs total AA supplement DIETARY_SUPPLEMENT

7 g as bolus

Also known as: 7 g EAA + 40% LEU

Oral EAA vs total AA supplement

Eligibility Criteria

• Age: 10 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects who already have a diagnosis of CF based on universal diagnostic criteria.
• Age 14 to 21 years at the time of enrollment
• Under routine medical control at the CF center of ACH
• Admitted to the ACH for treatment of pulmonary exacerbation of CF disease.
• Improvement in lung function (FEV1) at the time of enrollment back to baseline values (as determined in the clinically stable pre-hospital period)
• Central or peripheral venous line in place
• 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.

You may not qualify if:

• Established diagnosis of Diabetes Mellitus
• Presence of fever within the last 3 days
• Unstable metabolic diseases including liver (cirrhosis) or renal disease
• Chronic respiratory failure with cor pulmonale
• Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment
• Any other condition according to the principle investigator or study physician would interfere with collecting study samples
• Failure to give assent / informed consent

Sponsors & Collaborators

• Texas A&M University: lead
• Arkansas Children's Hospital Research Institute: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• Engelen MP, Com G, Deutz NE. Increased whole body hydroxyproline production as assessed by a new stable isotope technique is associated with hip and spine bone mineral loss in cystic fibrosis. Clin Nutr. 2014 Dec;33(6):1117-21. doi: 10.1016/j.clnu.2013.12.008. Epub 2013 Dec 29.

  PMID: 24423745 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Excitatory Amino Acids; Leucine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nicolaas EP Deutz, MD, PhD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 27, 2010
• First Posted: July 29, 2010
• Study Start: July 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: February 1, 2013
• Last Updated: August 11, 2015

Record last verified: 2015-08

Locations

US (1)