Fatty Acid Oxidation Disorders & Body Weight Regulation Grant

Trifunctional Protein Deficiency Clinical Trial

Official title:

Fatty Acid Oxidation Disorders & Body Weight Regulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00654004
• Other study ID #: DK71869
• Secondary ID: K01DK071869
• Status: Completed
• Phase: N/A
• First received: April 3, 2008
• Last updated: April 18, 2013
• Start date: April 2006
• Est. completion date: January 2011

Study information

• Verified date: April 2013
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

Several hormones involved in body weight regulation increase the subject's ability to burn fat for energy. The purpose of this study is to investigate how burning fat for energy may affect those hormones and body weight in children. The study will also determine if eating a diet higher in protein alters the amount of fat you burn and how these hormones control body weight.

Description:

A role for mitochondrial fatty acid oxidation in the peripheral signaling cascade of leptin, adiponectin and insulin has recently been proposed from animal studies but has not been investigated in humans. Children with trifunctional protein (TFP, including deficiency of long-chain hydroxyacyl-CoA dehydrogenase) and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, inherited disorders of long-chain fatty acid ß-oxidation, lack an ability to oxidize fatty acids for energy. They have increased levels of body fat and circulating leptin and a high incidence of obesity. Current therapy for children with these disorders is based on frequent meals and consuming a low fat, very high carbohydrate diet. Despite treatment, exercise induced rhabdomyolysis is a common complication of TFP and VLCAD deficiency that frequently leads to exercise avoidance. The effects of these genetic defects on body composition and weight regulation have not been investigated. The contribution of fatty-acid oxidation during moderate intensity exercise in children has also not been reported.

Two groups of subjects were recruited: one group of subjects had a long-chain fatty acid oxidation disorder (n=13). The other group is a group of controls (n=16). We studied peripheral signals of body weight regulation, glucose tolerance, body composition, and exercise metabolism in subjects with a long-chain fatty acid oxidation disorder compared to normal controls.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 7 Years to 40 Years

Eligibility

Inclusion Criteria:

• confirmed diagnosis of TFP, LCHAD, CPT2 or VLCAD deficiency

• at least 7 years of age

• willingness to complete overnight admission

• generally healthy

Exclusion Criteria:

• inclusion in another research project that alters macronutrient intake

• diabetes, thyroid disease or other endocrine dysfunction that alters body composition.

• pregnancy

• anemia

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Body Weight
• Cardiomyopathies
• Lipid Metabolism, Inborn Errors
• Mitochondrial Myopathies
• Protein Deficiency
• Rhabdomyolysis
• Trifunctional Protein Deficiency

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
Oregon Health and Science University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Oregon State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	An Outcome of This Study is the Difference in Percent Body Fat (%BF) Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Normal Controls.	Body composition by DEXA was measured in subjects with a long-chain fatty acid oxidation disorder (n=13). Twelve age, sex and BMI matched controls and 4 heterozygotes for a long-chain fatty acid oxidation disorder were recruited who also completed body composition measures. The difference in body composition between subjects and age matched controls was compared by t-test.	Subjects will be compared to controls at one point in time.	No
Primary	An Outcome of This Study is the Difference in Glucose Tolerance Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Normal Controls.	Glucose tolerance was estimated by the Matsuda Index using glucose and insulin values from a standard oral glucose tolerance test. The Matsuda Index is calculated by the following formula: 10,000/ sq root of (fasting glucose mg/dl X fasting insulin in units/ml) X (mean glucose (mg/dl) X mean insulin (units/ml) and correlates with insulin sensitivity measured by the gold standard method of a hyperinsulinemic euglycemic clamp. Values of 2.5 or greater are considered insulin sensitive. Values of 2.4 or less are considered insulin resistance.; The Matsuda Index of Insulin Sensitivity was measured in subjects with a long-chain fatty acid oxidation disorder (n=12). Twelve age, sex and BMI matched controls and 4 heterozygotes for a long-chain fatty acid oxidation disorder were recruited who also completed an oral glucose tolerance test. The difference in Mastuda Index between subjects and age matched controls was compared by t-test.	Subjects will be compared to controls at one point in time.	No
Secondary	The Difference in Plasma Adiponectin Levels Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test	Fasting total adiponectin levels in ug/ml were measured in both groups (subjects with a long-chain fatty acid oxidation disorder). The differences between groups were compared with a t-test	Fasting total adiponectin (ug/ml)	No
Secondary	The Difference in Plasma Leptin Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test	Fasting leptin in ng/kg fat mass were measured in both groups (subjects with a long-chain fatty acid oxidation disorder; controls). The differences between groups were compared with a t-test	Fasting leptin levels ng per kg of fat mass	No
Secondary	The Difference in Plasma Insulin Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test	Fasting insulin levels in uU/ml were measured in both groups. The differences between groups were compared with a t-test	Fasting insulin levels uUnits/ml	No