Trial record 4 of 4 for:    "Mitochondrial trifunctional protein deficiency"

Fatty Acid Oxidation Disorders & Body Weight Regulation Grant

This study has been completed.
Sponsor:
Collaborators:
Oregon State University
Information provided by (Responsible Party):
Melanie B Gillingham, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT00654004
First received: April 3, 2008
Last updated: April 18, 2013
Last verified: April 2013
  Purpose

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.


Condition
Trifunctional Protein Deficiency

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Fatty Acid Oxidation Disorders & Body Weight Regulation

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • 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. [ Time Frame: Subjects will be compared to controls at one point in time. ] [ Designated as safety issue: No ]
    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.

  • An Outcome of This Study is the Difference in Glucose Tolerance Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Normal Controls. [ Time Frame: Subjects will be compared to controls at one point in time. ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • The Difference in Plasma Adiponectin Levels Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test [ Time Frame: Fasting total adiponectin (ug/ml) ] [ Designated as safety issue: No ]
    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

  • The Difference in Plasma Leptin Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test [ Time Frame: Fasting leptin levels ng per kg of fat mass ] [ Designated as safety issue: No ]
    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

  • The Difference in Plasma Insulin Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test [ Time Frame: Fasting insulin levels uUnits/ml ] [ Designated as safety issue: No ]
    Fasting insulin levels in uU/ml were measured in both groups. The differences between groups were compared with a t-test


Biospecimen Retention:   Samples Without DNA

Blood and urine samples. Body composition and energy expenditure data. MRI/MRS images.


Enrollment: 26
Study Start Date: April 2006
Study Completion Date: January 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
Subjects
Subjects are patients with a long-chain fatty acid oxidation disorder including CPT2, VLCAD, TFP or LCHAD deficiency.
Controls
Subjects do not have a fatty acid oxidation disorder.

Detailed 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.

  Eligibility

Ages Eligible for Study:   7 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Subjects were patients with a diagnosis of mitochondrial trifunctional protein, long-chain 3-hydroxyacylCoA dehydrogenase, very long-chain acylCoA dehydrogenase or carnitine palmitoyltransferase 2 deficency. They were recruited through advertisements on the FAO support website, or physician referral. Control subjects were from the greater Portland area. They were recruited via adverstisements at OHSU.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00654004

Locations
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Oregon State University
Investigators
Principal Investigator: Melanie B. Gillingham, PhD Oregon Health and Science University
  More Information

No publications provided by Oregon Health and Science University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Melanie B Gillingham, Assistant Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT00654004     History of Changes
Other Study ID Numbers: DK71869, K01DK071869
Study First Received: April 3, 2008
Results First Received: December 11, 2012
Last Updated: April 18, 2013
Health Authority: United States: Federal Government

Keywords provided by Oregon Health and Science University:
trifunctional
protein
deficiency
TFP
weight
regulation

Additional relevant MeSH terms:
Body Weight
Protein Deficiency
Lipid Metabolism, Inborn Errors
Cardiomyopathies
Rhabdomyolysis
Mitochondrial Myopathies
Signs and Symptoms
Deficiency Diseases
Malnutrition
Nutrition Disorders
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Metabolic Diseases
Heart Diseases
Cardiovascular Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Mitochondrial Diseases

ClinicalTrials.gov processed this record on August 21, 2014