Clincosm LogoSign in Get a demo

Fatty Acid Oxidation Defects and Insulin Sensitivity

Sponsor
Oregon Health and Science University (Other)
Overall Status
Completed
CT.gov ID
NCT02517307
Collaborator
(none)
52
Enrollment
1
Location
2
Arms
60.9
Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
N/A

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

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Role of Fatty Acid Oxidation Defects in Insulin Sensitivity
Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Jan 1, 2021
Actual Study Completion Date :
Mar 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: glycerol/saline

Glycerol/Saline infusion

Drug: Glycerol/Saline
Co-infusion of a glycerol/saline solutions during a hyperinsulinemic euglycemic clamp

Drug: 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.
Experimental: intralipid

Intralipid/Heparin infusion

Drug: Intralipid/Heparin
Co-infusion of intralipid and heparin solutions during a hyperinsulinemic euglycemic clamp

Drug: 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.

Outcome Measures

Primary Outcome Measures

  1. Glucose Disposal Rate (Rd)- the rate of glucose infusion to maintain euglycemia during steady state insulin infusion in ml/kg/hr [5 hours]

    Amount of glucose disposal during hyperinsulinemic euglycemic clamp

Secondary Outcome Measures

  1. Endogenous glucose production (Ra) - calculated by the equations of Steele during steady state in ml/kg/hr [5 hours]

    Amount of glucose endogenously synthesized and secreted into circulation

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Oregon Health & Science University Portland Oregon United States 97239

Sponsors and Collaborators

  • Oregon Health and Science University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Melanie B Gillingham, Associate Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT02517307
Other Study ID Numbers:
  • OHSU11258
First Posted:
Aug 7, 2015
Last Update Posted:
Mar 9, 2021
Last Verified:
Mar 1, 2021
Additional relevant MeSH terms:
Insulin Resistance
Protein Deficiency
Heparin
Soybean oil, phospholipid emulsion
Glycerol

Study Results

No Results Posted as of Mar 9, 2021