- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03539809
Branched Chain Amino Acids Ratio in Medical Foods
Determining the Optimal Ratio of Branched Chain Amino Acids in Medical Foods for Methylmalonic and Propionic Acidemias (MMA/PROP)
Study Overview
Detailed Description
Purpose:
The purpose of this study is to use the minimally invasive Indicator Amino Acid Oxidation (IAAO) method in healthy school-aged children to determine the optimal ratio of BCAA in current medical foods used by MMA/PROP subjects. We will recruit healthy children to test our hypothesis.
Hypothesis:
- The IAAO will be high (suggesting low protein synthesis) at high leucine levels and will be low (suggesting optimal protein synthesis) when leucine levels are reduced and at a better-balanced ratio of leucine to isoleucine and valine.
- Children will have low levels of urine excretion of isoleucine and valine, with high leucine urinary excretion, when given the high ratio of leucine to valine and isoleucine. With the reduction of leucine intake in the diet, the urinary concentration of both isoleucine and valine will normalize.
Justification:
The use of medical foods as a sole source of energy and protein in patients with MMA/PROP has been discouraged. The recommendations state that such medical foods should be only used for patients who can't consume their RDA from natural protein. Since most of these patients are poor eaters, and at risk for malnutrition, they depend on medical foods as an easy tolerable source of energy and protein. The medical foods formulated for MMA/PROP contain imbalanced BCAA ratio (high leucine to minimal or no valine and isoleucine). The high leucine levels antagonize the other two BCAA and even suppresses their plasma and urine levels below normal. Determining the optimal ratio of BCAA is necessary to optimize protein synthesis, growth and prevent the accumulation of toxic metabolites. This proposal will focus on applying stable isotope tracers in healthy children to examine different intakes of leucine while keeping the amount of valine and isoleucine restricted as per the recommendations. Using the minimally invasive indicator amino acid technique (IAAO), and L-1-13C-Phenylalanine as the indicator amino acid for protein synthesis, the optimal amount of leucine to be added in one of the most commonly used medical food for these patients will be tested. In addition, the leucine intake which normalizes urine isoleucine and valine excretion will also be determined to be useful for patient management. Starting with the studies on healthy children ages 6-10 years to allow for characterization of the metabolic response to the different leucine intakes. Consequently, based on the results we obtain, we will be able to design the studies in MMA/PROP patients with the appropriate BCAA ratios to test.
Objectives:
- Our primary objective is to examine the impact of reducing leucine levels from the current high doses in medical foods, sequentially, while holding isoleucine and valine at MMA/PROP recommended intakes, on protein synthesis using the IAAO technique in healthy children (6-10y).
- Our secondary objective is to determine the impact of reducing leucine levels from the current high doses in medical foods, sequentially, while holding isoleucine and valine at MMA/PROP recommended intakes, on urinary excretion of BCAA.
Research Design:
This is a repeated measure study design involving 1 pre-study visit and 6 studies visits for each child, approximately one week apart from each other.
Statistical Analysis:
Results will be expressed as means ± SDs. Repeated Measures ANOVA will be used to assess the relationship of phenylalanine oxidation, and BCAA urinary excretion to the variable BCAA intakes using SAS statistical software (version 9.4; SAS Institute, Cary, NC). In all cases, the difference will be considered significant at P < 0.05. Repeated measure ANOVA will be used to measure the difference between means of F13CO2 oxidations in response to 6 leucine test intakes, as well as means of BCAA urinary excretions. When warranted, post hoc analysis will be performed using Tukey's multiple comparisons test to confirm where the differences occur between different conditions (leucine test intakes).
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Rajavel Elango, Ph.D
- Phone Number: 4911 604 875 2000
- Email: relango@bcchr.ubc.ca
Study Contact Backup
- Name: Haneen Saleemani, MSc
- Phone Number: 4607 604 875 2000
- Email: haneen.saleemani@bcchr.ubc.ca
Study Locations
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V5Z4H4
- Recruiting
- BC Children's Hospital Research Institute, University of British Columbia
-
Contact:
- Rajavel Elango, Ph.D
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy school-aged children 6-10y
- Normal weight
- Normal eating habits
- English speaking children
Exclusion Criteria:
- Children under 6 years old, or over 10 years old.
- Children who are currently ill, with a fever, cold, vomiting or diarrhea.
- Children outside of normal weight parameters (3rd -85th percentiles for weight).
- Children with claustrophobia.
- Children currently or recently taking medication or antibiotics.
- Children with food allergies.
- Children who cannot speak, write and read in English
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BCAA Ratio
Different Branched-chain amino acid (BCAA) ratios will be tested.
BCAA are comprised of 3 different amino acids (leucine, isoleucine and valine).
The ratios among these 3 amino acids will be tested at 6 different ratios.
Each intervention will be for 8hours.
|
6 different ratios of the Branched-chain Amino Acids (BCAA) will be tested for 8 hours each.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
13C Phenylalanine Oxidation
Time Frame: 8 hours
|
Breath and Urine samples will be collected during the study to measure 13C Phenylalanine oxidation
|
8 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Urinary Branched Chain amino acids excretion
Time Frame: 8 hours
|
Urine samples will be collected during the study to measure BCAA urinary excretion
|
8 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rajavel Elango, Ph.D, University of British Columbia
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- H18-00439
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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