Trifunctional Protein DeficiencyNCT00654004
Fatty Acid Oxidation Disorders & Body Weight Regulation Grant
An observational study of Trifunctional Protein Deficiency, run by Oregon Health and Science University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 7 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Trifunctional Protein Deficiency
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Jan 2011
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
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.
Who may be able to join
- confirmed diagnosis of TFP, LCHAD, CPT2 or VLCAD deficiency
- at least 7 years of age
- willingness to complete overnight admission
- generally healthy
Who cannot join
- inclusion in another research project that alters macronutrient intake
- diabetes, thyroid disease or other endocrine dysfunction that alters body composition.
- pregnancy
- anemia
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: Fatty Acid Oxidation Disorders & Body Weight Regulation
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.
Read the 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.
- Conditions
- Trifunctional Protein Deficiency
- Keywords
- trifunctional, protein, deficiency, TFP, weight, regulation
- Medical subject headings
- Trifunctional Protein Deficiency With Myopathy And Neuropathy, Body Weight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Subjects will be compared to controls at one point in time.
Secondary outcomes (3)
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
Measured: Fasting total adiponectin (ug/ml)
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
Measured: 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
Measured: Fasting insulin levels uUnits/ml
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2008 (estimated)
- Study startApr 2006
- Primary completionSep 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Trifunctional Protein DeficiencyStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Oregon State University
- Responsible party
- Principal investigator, Melanie B Gillingham, Oregon Health and Science University
- Investigators
- Melanie B. Gillingham, PhD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00654004
- Sponsor's protocol ID
- DK71869
- Other IDs
- K01DK071869
- Status last verified
- Apr 2013
- First submitted
- 3 Apr 2008
- Last updated
- 22 Apr 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 22030098
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fatty Acid Oxidation Disorders & Body Weight Regulation
- ClinicalTrials.gov ID
- NCT00654004
- Acronym / sponsor ID
- DK71869
- Conditions
- Trifunctional Protein Deficiency
- Keywords
- trifunctional, protein, deficiency, TFP, weight, regulation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Oregon State University
- Study start
- Apr 2006
- Primary completion
- Sep 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 7 Apr 2008 (estimated)
- Results
- Posted 22 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 7 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (4 listed)
- confirmed diagnosis of TFP, LCHAD, CPT2 or VLCAD deficiency
- at least 7 years of age
- willingness to complete overnight admission
- generally healthy
Key exclusion criteria (4 listed)
- inclusion in another research project that alters macronutrient intake
- diabetes, thyroid disease or other endocrine dysfunction that alters body composition.
- pregnancy
- anemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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.
3 secondary outcomes
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)
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22030098Behrend 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melanie B. Gillingham, PhD principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Trifunctional Protein Deficiency, run by Oregon Health and Science University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Subjects will be compared to controls at one point in time.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00654004, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2013.