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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172301
• Other study ID #: 104738
• Status: Completed
• Phase: N/A
• First received: July 27, 2010
• Last updated: August 7, 2015
• Start date: July 2008
• Est. completion date: February 2013

Study information

• Verified date: August 2015
• Source: Texas A&M University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 21 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Dietary Supplement:
• Essential amino acid intake + Leucine vs total AA supplement
7 g as bolus

Locations

Country	Name	City	State
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas

Sponsors (2)

Lead Sponsor	Collaborator
Texas A&M University	Arkansas Children's Hospital Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Whole body collagen breakdown rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years	No
Secondary	Urea turnover rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years	No
Secondary	Arginine turnover rate	Measured in postabsorptive state	Up to 2 years	No
Secondary	Liver protein synthesis rate	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years	No
Secondary	Resting Energy expenditure	Measured in postabsorptive state	Up to 2 years	No
Secondary	Insulin kinetics	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years	No
Secondary	Amino acid kinetics	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years	No
Secondary	Glucose kinetics	Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement	Up to 2 years	No
Secondary	Fat-free mass	Characterization of subjects	Up to 2 years	No