Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02517307
Other study ID # OHSU11258
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date February 2016
Est. completion date March 2021

Study information

Verified date December 2023
Source Oregon Health and Science University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 41
Est. completion date March 2021
Est. primary completion date January 2021
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: - 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Intralipid/Heparin
Co-infusion of intralipid and heparin solutions during a hyperinsulinemic euglycemic clamp
Glycerol/Saline
Co-infusion of a glycerol/saline solutions during a hyperinsulinemic euglycemic clamp
Hyperinsulinemic euglycemic clamp
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.

Locations

Country Name City State
United States Oregon Health & Science University Portland Oregon

Sponsors (1)

Lead Sponsor Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Calculated during the last 30 minutes of a 300 minute clamp.
Secondary 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. Calculated during the last 30 minutes of a 300 minute clamp.
See also
  Status Clinical Trial Phase
Completed NCT02922933 - A Study to Examine the Effect of Omeprazole, Famotidine, and an Acidic Beverage on the Pharmacokinetics of Entinostat in Healthy Adult Subjects Phase 1
Completed NCT02922946 - Study to Determine the Effect of the Timing of a Meal on the Pharmacokinetics of Entinostat Phase 1
Completed NCT01250197 - Formulation Comparison in Normal Volunteers Phase 1
Completed NCT02051517 - Vitreous Chemistry Analysis N/A
Completed NCT01185418 - Evaluation of Negative Symptoms and Cognitive Function After Administration of Antipsychotics in Healthy Volunteer N/A
Recruiting NCT00182858 - Tissue Procurement for Biomedical Research
Completed NCT02828813 - Neural Mechanisms of Motor and Cognitive Networks
Completed NCT02146391 - Study to Evaluate the Effect of Food Upon the Pharmacokinetics of Androxal Phase 1
Terminated NCT00465842 - Protein Biomarker in Hepatocellular Carcinoma
Recruiting NCT02471352 - Studies of Dermatologic Diseases Biospecimen Acquisition Protocol
Terminated NCT01752231 - Optimization of Novel DCE-MRI Imaging Sequences for Cancer Therapy Monitoring N/A
Completed NCT01366352 - Pharmacokinetics and Bioavailability Comparison of Two Different Formulations of MNTX Tablets Phase 1
Not yet recruiting NCT01487486 - Proteomics & Glyco-Proteomic Analysis of Follicular Fluid N/A
Completed NCT03993587 - The Effect of Head and Shoulder Positioning on the Cross-sectional Area of the Subclavian Vein in Obese Adults
Completed NCT02860351 - The Effect of Head Positioning on the Cross-sectional Area of the Subclavian Vein. N/A
Completed NCT02113943 - Double Blind Randomized, Monocentric, Cross-over, Placebo-controlled Study to Evaluate the Effect of Citalopram on Motivation Phase 2