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| ID | Type | Description | Link |
|---|---|---|---|
| K01DK071869 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| Oregon State University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Melanie B. Gillingham, PhD | Oregon Health and Science University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22030098 | Derived | Behrend AM, Harding CO, Shoemaker JD, Matern D, Sahn DJ, Elliot DL, Gillingham MB. Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation. Mol Genet Metab. 2012 Jan;105(1):110-5. doi: 10.1016/j.ymgme.2011.09.030. Epub 2011 Oct 1. |
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After a subject had completed the protocol, potential control subjects were screened for age, gender and BMI that would allow for a 1 to 1 matching study design.
Subjects with a long-chain fatty acid oxidation disorder were recruited through announcements on disease specific websites, and referrals from metabolic physicians. Controls were recruited through the OHSU website and word of mouth.
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| ID | Title | Description |
|---|---|---|
| FG000 | Subjects | Subjects are patients with a long-chain fatty acid oxidation disorder including CPT2, VLCAD, TFP or LCHAD deficiency. |
| FG001 | Controls | Subjects do not have a fatty acid oxidation disorder. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Subjects | Subjects are patients with a long-chain fatty acid oxidation disorder including CPT2, VLCAD, TFP or LCHAD deficiency. |
| BG001 | Controls | Subjects do not have a fatty acid oxidation disorder. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Study design was based on 1 to 1 matching of subjects and controls. Thirteen subjects but only 12 controls completed the protocol. We report results of 12 subjects compared to 12 matched controls. | Posted | Mean | Standard Deviation | percentage of body fat | Subjects will be compared to controls at one point in time. |
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Adverse events were assessed during the study. No serious adverse events occurred during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Subjects | Subjects are patients with a long-chain fatty acid oxidation disorder including CPT2, VLCAD, TFP or LCHAD deficiency. |
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Trial included small number of subjects with a rare disorder of long-chain fatty acid oxidation. Subjects were predominately children and adolescents. There were some technical difficulties with recruitment and collection of all the outcomes.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Melanie Gillingham | Oregon Health & Science Univeristy | 503-494-1682 | gillingm@ohsu.edu |
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| ID | Term |
|---|---|
| C566945 | Trifunctional Protein Deficiency With Myopathy And Neuropathy |
| D001835 | Body Weight |
| ID | Term |
|---|---|
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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Blood and urine samples. Body composition and energy expenditure data. MRI/MRS images.
| 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 |
| 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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG001 | Controls | Subjects do not have a fatty acid oxidation disorder. |
|
|
| 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 | Study was designed as a one to one matching design. Thirteen subjects but only 12 controls completed the protocol. We report results of 12 subjects and 12 matched controls. | Posted | Mean | Standard Deviation | ug/ml | Fasting total adiponectin (ug/ml) |
|
|
|
| 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. | Study design was based on 1 to 1 matching of subjects and controls. Thirteen subjects but only 12 controls completed the protocol. We report results of 12 subjects compared to 12 matched controls. | Posted | Mean | Standard Deviation | units on a scale | Subjects will be compared to controls at one point in time. |
|
|
|
| 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 | Study was designed as a one to one matching design. Thirteen subjects but only 12 controls completed the protocol. We report results of 12 subjects and 12 matched controls. | Posted | Mean | Standard Deviation | ng/kg | Fasting leptin levels ng per kg of fat mass |
|
|
|
| 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 | Study was designed as a one to one matching design. Thirteen subjects but only 12 controls completed the protocol. Samples were missing on one subject so 11 subjects were compared to 11 controls. | Posted | Mean | Standard Deviation | uU/ml | Fasting insulin levels uUnits/ml |
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| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Controls | Subjects do not have a fatty acid oxidation disorder. | 0 | 12 | 0 | 12 |
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