Clinical trial NCT00654004: Fatty Acid Oxidation Disorders & Body Weight Regulation Grant
Official title: Fatty Acid Oxidation Disorders & Body Weight Regulation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Trifunctional Protein Deficiency
Keywords: trifunctional
protein
deficiency
TFP
weight
regulation
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Oregon State University
First posted: 2008-04-07
Enrollment: 26
Sex: ALL
Minimum age (years): 7
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief 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.

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 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

Primary outcomes:
measure: 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.
timeFrame: Subjects will be compared to controls at one point in time.
measure: An Outcome of This Study is the Difference in Glucose Tolerance Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Normal Controls.
timeFrame: Subjects will be compared to controls at one point in time.
Secondary outcomes:
measure: The Difference in Plasma Adiponectin Levels Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test
timeFrame: Fasting total adiponectin (ug/ml)
measure: The Difference in Plasma Leptin Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test
timeFrame: Fasting leptin levels ng per kg of fat mass
measure: The Difference in Plasma Insulin Between Subjects With a Long-chain Fatty Acid Oxidation Disorder and Matched Controls Was Compared by T-test
timeFrame: Fasting insulin levels uUnits/ml
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Melanie B. Gillingham, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.