Very Long-chain Acyl-CoA Dehydrogenase DeficiencyNCT02517307
Fatty Acid Oxidation Defects and Insulin Sensitivity
A study testing Intralipid/Heparin, Glycerol/Saline and Hyperinsulinemic euglycemic clamp in people with Very Long-chain Acyl-CoA Dehydrogenase Deficiency and Trifunctional Protein Deficiency, run by Oregon Health and Science University at 1 site in United States.
Trial summary
The purpose of this study is to learn more about what causes insulin resistance. It has been suggested that proper breakdown of fat into energy (oxidation) in the body is important to allow insulin to keep blood sugar in the normal range. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Very Long-chain Acyl-CoA Dehydrogenase Deficiency, Trifunctional Protein Deficiency, Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency
- What is being tested?
- Intralipid/Heparin, Glycerol/Saline and Hyperinsulinemic euglycemic clamp
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to Mar 2021
- Phase
- Interventional
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- confirmed diagnosis of VLCAD, LCHAD, TFP or MCAD deficiency or same gender, age and BMI as a subject with a fatty acid oxidation disorder
- ability to travel to Oregon Health \& Science University, Portland, Oregon
- ability and willingness to complete the protocol
Who cannot join
- hemoglobin <10g/dl, international normalized ratio (INR) >1.2 Prothrombin time (PTT) >36 sec, Platelets <150K/mm3
- pregnant or lactating females
- endocrine disorder such as diabetes or untreated thyroid disease
- cardiovascular disease or elevated plasma lipids
- regularly taking meds that strongly affect bleeding, bruising or platelets
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: Role of Fatty Acid Oxidation Defects in Insulin Sensitivity
The purpose of this study is to learn more about what causes insulin resistance. It has been suggested that proper breakdown of fat into energy (oxidation) in the body is important to allow insulin to keep blood sugar in the normal range. The investigators want to know if having one of the fatty acid oxidation disorders could have an influence on insulin action. Fatty acid oxidation disorders are genetic disorders that inhibit one of the enzymes that converts fat into energy. The investigators will study both normal healthy people and people with a long-chain fatty acid oxidation disorder.
Read the detailed description
The overall goal of this proposal is to investigate the effects of disordered mitochondrial fatty acid oxidation on insulin resistance in humans. Mitochondrial dysfunction has been implicated in the development of insulin resistance and type 2 diabetes during excess dietary fat intake and from increased release of endogenous free fatty acids , such as occurs in obesity. Controversy exists, however, as to whether this insulin resistance results from intrinsic defects in mitochondrial energy utilization or from abnormalities resulting from excess free fatty acid flux, as well as the role that subsequent accumulation of cellular metabolic intermediates play in impaired insulin signaling.
To address these controversies, the investigators will study a unique population of patients with inherited defects in each of the three mitochondrial enzymes in the fatty acid oxidation pathway: 1) very long-chain acyl-CoA dehydrogenase (VLCAD); 2) trifunctional protein (TFP, which includes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)); and 3) medium-chain acyl-CoA dehydrogenase (MCAD). These proteins are required for the oxidation of sequentially shorter fatty acids . The investigators will test the hypothesis that intrinsic defects in mitochondrial function involving oxidation of long-chain, but not medium-chain, fatty acids are sufficient to prevent intralipid-induced insulin resistance.
- Conditions
- Very Long-chain Acyl-CoA Dehydrogenase Deficiency, Trifunctional Protein Deficiency, Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency, Medium-chain Acyl-CoA Dehydrogenase Deficiency, Normal Volunteers, Carnitine Palmitoyltransferase II Deficiency, Myopathic
- Being tested
- Intralipid/Heparin, Glycerol/Saline, Hyperinsulinemic euglycemic clamp
- Medical subject headings
- VLCAD deficiency, Trifunctional Protein Deficiency With Myopathy And Neuropathy, Medium chain acyl CoA dehydrogenase deficiency, Carnitine Palmitoyltransferase II Deficiency, Late-Onset
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid/HeparinDrug
Co-infusion of intralipid and heparin solutions during a hyperinsulinemic euglycemic clamp
Glycerol/SalineDrug
Co-infusion of a glycerol/saline solutions during a hyperinsulinemic euglycemic clamp
Hyperinsulinemic euglycemic clampDrug
Infusion of insulin at at 40 mU/m2/min for 5 hours. Blood glucose will be monitored every 5 min during the insulin infusion and euglycemia will be maintained throughout the clamp by infusing 20% dextrose at a variable rate.
| Study group | Role | What they receive |
|---|---|---|
| glycerol/saline FAOD | Experimental | Glycerol/Saline co-infusion hyperinsulinemic euglycemic clamp among subjects with a fatty acid oxidation disorder (FAOD) Receives: Drug: Glycerol/Saline; Drug: Hyperinsulinemic euglycemic clamp |
| intralipid FAOD | Experimental | Intralipid/Heparin co-infusion hyperinsulinemic euglycemic clamp among subjects with a fatty acid oxidation disorder (FAOD) Receives: Drug: Intralipid/Heparin; Drug: Hyperinsulinemic euglycemic clamp |
| glycerol/saline Control | Experimental | Glycerol/Saline co-infusion hyperinsulinemic euglycemic clamp among normal matched control subjects (control) Receives: Drug: Glycerol/Saline; Drug: Hyperinsulinemic euglycemic clamp |
| intralipid Control | Experimental | Intralipid/Heparin co-infusion hyperinsulinemic euglycemic clamp among normal matched control subjects (control) Receives: Drug: Intralipid/Heparin; Drug: Hyperinsulinemic euglycemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose Disposal Rate (Rd)- the Rate of Glucose Infusion to Maintain Euglycemia During Steady State Insulin Infusion in mg/Min
Insulin infusion induces glucose disposal into muscle and adipose tissue in insulin sensitive participants. During the glycerol co-infusion, glucose disposal will be high. Intralipid co-infusion can induce a temporary insulin resistant state. During the intralipid co-infusion, glucose disposal will be decreased. We are comparing how intralipid dampens glucose disposal between participants with a FAOD and matched control participants. Glucose disposal is measured by measuring the ratio of deuterated glucose to unlabeled glucose at the beginning and end of the clamp. The calculated glucose disposal rate or RD is mg of glucose taken into muscle and adipose tissue per minute.
Measured: Calculated during the last 30 minutes of a 300 minute clamp.
Secondary outcomes (1)
Endogenous Glucose Production (Ra) - Calculated by the Equations of Steele During Steady State in mg/Min
Infusion of insulin will suppress endogenous glucose production from the liver in insulin sensitive people. Insulin infusion with glycerol should suppress the endogenous glucose production in the liver but intralipid induces a temporary state of insulin resistance and the decrease in endogenous glucose production or Ra will be blunted with intralipid co-infusion. We are looking at the difference in Ra with intralipid between participants with a FAOD and matched control participants. Ra or endogenous glucose production during high insulin is measured in mg new glucose synthesized per minute.
Measured: Calculated during the last 30 minutes of a 300 minute clamp.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2015 (estimated)
- Study startFeb 2016
- Primary completionJan 2021
- Study completionMar 2021
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.
- Other trials for Very Long-chain Acyl-CoA Dehydrogenase DeficiencyStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Melanie B Gillingham, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02517307
- Sponsor's protocol ID
- OHSU11258
- Status last verified
- Dec 2023
- First submitted
- 2 Jul 2015
- Last updated
- 30 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Fatty Acid Oxidation Defects in Insulin Sensitivity
- ClinicalTrials.gov ID
- NCT02517307
- Acronym / sponsor ID
- OHSU11258
- Conditions
- Very Long-chain Acyl-CoA Dehydrogenase Deficiency, Trifunctional Protein Deficiency, Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency, Medium-chain Acyl-CoA Dehydrogenase Deficiency, Normal Volunteers, Carnitine Palmitoyltransferase II Deficiency, Myopathic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Jan 2021 (actual)
- Study completion
- Mar 2021 (actual)
- First posted
- 7 Aug 2015 (estimated)
- Results
- Posted 30 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn more about what causes insulin resistance. It has been suggested that proper breakdown of fat into energy (oxidation) in the body is important to allow insulin to keep blood sugar in the normal range. The investigators want to know if having one of the fatty acid oxidation disorders could have an influence on insulin action. Fatty acid oxidation disorders are genetic disorders that inhibit one of the enzymes that converts fat into energy. The investigators will study both normal healthy people and people with a long-chain fatty acid oxidation disorder.
Detailed description
The overall goal of this proposal is to investigate the effects of disordered mitochondrial fatty acid oxidation on insulin resistance in humans. Mitochondrial dysfunction has been implicated in the development of insulin resistance and type 2 diabetes during excess dietary fat intake and from increased release of endogenous free fatty acids , such as occurs in obesity. Controversy exists, however, as to whether this insulin resistance results from intrinsic defects in mitochondrial energy utilization or from abnormalities resulting from excess free fatty acid flux, as well as the role that subsequent accumulation of cellular metabolic intermediates play in impaired insulin signaling.
To address these controversies, the investigators will study a unique population of patients with inherited defects in each of the three mitochondrial enzymes in the fatty acid oxidation pathway: 1) very long-chain acyl-CoA dehydrogenase (VLCAD); 2) trifunctional protein (TFP, which includes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)); and 3) medium-chain acyl-CoA dehydrogenase (MCAD). These proteins are required for the oxidation of sequentially shorter fatty acids . The investigators will test the hypothesis that intrinsic defects in mitochondrial function involving oxidation of long-chain, but not medium-chain, fatty acids are sufficient to prevent intralipid-induced insulin resistance.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| glycerol/saline FAOD | Experimental | Drug: Glycerol/Saline, Drug: Hyperinsulinemic euglycemic clampGlycerol/Saline co-infusion hyperinsulinemic euglycemic clamp among subjects with a fatty acid oxidation disorder (FAOD) |
| intralipid FAOD | Experimental | Drug: Intralipid/Heparin, Drug: Hyperinsulinemic euglycemic clampIntralipid/Heparin co-infusion hyperinsulinemic euglycemic clamp among subjects with a fatty acid oxidation disorder (FAOD) |
| glycerol/saline Control | Experimental | Drug: Glycerol/Saline, Drug: Hyperinsulinemic euglycemic clampGlycerol/Saline co-infusion hyperinsulinemic euglycemic clamp among normal matched control subjects (control) |
| intralipid Control | Experimental | Drug: Intralipid/Heparin, Drug: Hyperinsulinemic euglycemic clampIntralipid/Heparin co-infusion hyperinsulinemic euglycemic clamp among normal matched control subjects (control) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- confirmed diagnosis of VLCAD, LCHAD, TFP or MCAD deficiency or same gender, age and BMI as a subject with a fatty acid oxidation disorder
- ability to travel to Oregon Health \& Science University, Portland, Oregon
- ability and willingness to complete the protocol
Key exclusion criteria (5 listed)
- hemoglobin <10g/dl, international normalized ratio (INR) >1.2 Prothrombin time (PTT) >36 sec, Platelets <150K/mm3
- pregnant or lactating females
- endocrine disorder such as diabetes or untreated thyroid disease
- cardiovascular disease or elevated plasma lipids
- regularly taking meds that strongly affect bleeding, bruising or platelets
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intralipid/HeparinCo-infusion of intralipid and heparin solutions during a hyperinsulinemic euglycemic clamp | Drug | intralipid Control, intralipid FAOD |
| Glycerol/SalineCo-infusion of a glycerol/saline solutions during a hyperinsulinemic euglycemic clamp | Drug | glycerol/saline Control, glycerol/saline FAOD |
| Hyperinsulinemic euglycemic clampInfusion of insulin at at 40 mU/m2/min for 5 hours. Blood glucose will be monitored every 5 min during the insulin infusion and euglycemia will be maintained throughout the clamp by infusing 20% dextrose at a variable rate. | Drug | glycerol/saline Control, glycerol/saline FAOD, intralipid Control, intralipid FAOD |
Primary outcome
Glucose Disposal Rate (Rd)- the Rate of Glucose Infusion to Maintain Euglycemia During Steady State Insulin Infusion in mg/Min
Time frame: Calculated during the last 30 minutes of a 300 minute clamp.
Insulin infusion induces glucose disposal into muscle and adipose tissue in insulin sensitive participants. During the glycerol co-infusion, glucose disposal will be high. Intralipid co-infusion can induce a temporary insulin resistant state. During the intralipid co-infusion, glucose disposal will be decreased. We are comparing how intralipid dampens glucose disposal between participants with a FAOD and matched control participants. Glucose disposal is measured by measuring the ratio of deuterated glucose to unlabeled glucose at the beginning and end of the clamp. The calculated glucose disposal rate or RD is mg of glucose taken into muscle and adipose tissue per minute.
1 secondary outcome
Endogenous Glucose Production (Ra) - Calculated by the Equations of Steele During Steady State in mg/Min
Time frame: Calculated during the last 30 minutes of a 300 minute clamp.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intralipid/Heparin, Glycerol/Saline and Hyperinsulinemic euglycemic clamp in people with Very Long-chain Acyl-CoA Dehydrogenase Deficiency and 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 3 inclusion and 5 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 30 Jan 2024. 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 30 Jan 2024). 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?
Glucose Disposal Rate (Rd)- the Rate of Glucose Infusion to Maintain Euglycemia During Steady State Insulin Infusion in mg/Min (time frame: Calculated during the last 30 minutes of a 300 minute clamp.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jan 2024.