- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00654004
Fatty Acid Oxidation Disorders & Body Weight Regulation Grant
Fatty Acid Oxidation Disorders & Body Weight Regulation
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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 Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Subjects
Subjects are patients with a long-chain fatty acid oxidation disorder including CPT2, VLCAD, TFP or LCHAD deficiency.
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Controls
Subjects do not have a fatty acid oxidation disorder.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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.
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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.
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Subjects will be compared to controls at one point in time.
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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.
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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)
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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
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Fasting total adiponectin (ug/ml)
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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
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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
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Fasting leptin levels ng per kg of fat mass
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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
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Fasting insulin levels in uU/ml were measured in both groups.
The differences between groups were compared with a t-test
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Fasting insulin levels uUnits/ml
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Melanie B. Gillingham, PhD, Oregon Health and Science University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DK71869
- K01DK071869 (U.S. NIH Grant/Contract)
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.
Clinical Trials on Trifunctional Protein Deficiency
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Oregon Health and Science UniversityNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Oregon...TerminatedPeripheral Neuropathy | Mitochondrial Trifunctional Protein DeficiencyUnited States
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Oregon Health and Science UniversityUniversity of PittsburghCompletedVery Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency | Carnitine Palmitoyltransferase 2 (CPT2) Deficiency | Mitochondrial Trifunctional Protein (TFP) Deficiency | Long-chain 3 hydroxyacylCoA Dehydrogenase (LCHAD) DeficiencyUnited States
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Oregon Health and Science UniversityRecruitingTrifunctional Protein Deficiency | Very Long Chain Acyl Coa Dehydrogenase Deficiency | Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency | Carnitine Palmitoyltransferase Deficiency 2United States
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Ultragenyx Pharmaceutical IncCompletedCarnitine Palmitoyltransferase (CPT I or CPT II) Deficiency | Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency | Long-chain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency | Trifunctional Protein (TFP) Deficiency | Carnitine-acylcarnitine Translocase (CACT) DeficiencyUnited States, United Kingdom
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Ultragenyx Pharmaceutical IncCompletedLong-chain Fatty Acid Oxidation Disorders (LC-FAOD) | Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency | Trifunctional Protein (TFP) Deficiency | Carnitine Palmitoyltransferase (CPT II) Deficiency | Longchain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) DeficiencyUnited States, United Kingdom
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Oregon Health and Science UniversityCompletedTrifunctional Protein Deficiency | Carnitine Palmitoyltransferase 2 Deficiency | Very Long-chain Acyl-CoA Dehydrogenase Deficiency | Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency
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Oregon Health and Science UniversityCompletedNormal Volunteers | Trifunctional Protein Deficiency | Very Long-chain Acyl-CoA Dehydrogenase Deficiency | Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency | Medium-chain Acyl-CoA Dehydrogenase Deficiency | Carnitine Palmitoyltransferase II Deficiency, MyopathicUnited States
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An Hsin QingShui ClinicCompleted
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United States Army Research Institute of Environmental...RecruitingStress, Physiological | Energy Supply; Deficiency | Energy Supply; Deficiency, SevereUnited States
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University of ReadingBiotechnology and Biological Sciences Research Council; The Norwegian Institute... and other collaboratorsNot yet recruiting