Fatty Acid Oxidation Defects and Insulin Sensitivity

NCT02517307 | Completed Results

• 1 other identifier: OHSU11258
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Endogenous Glucose Production (Ra) - Calculated by the Equations of Steele During Steady State in mg/Min

  Calculated during the last 30 minutes of a 300 minute clamp.

Study Arms (4)

glycerol/saline FAOD

EXPERIMENTAL

Glycerol/Saline co-infusion hyperinsulinemic euglycemic clamp among subjects with a fatty acid oxidation disorder (FAOD)

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)

Drug: Intralipid/Heparin; Drug: Hyperinsulinemic euglycemic clamp

glycerol/saline Control

EXPERIMENTAL

Glycerol/Saline co-infusion hyperinsulinemic euglycemic clamp among normal matched control subjects (control)

Drug: Glycerol/Saline; Drug: Hyperinsulinemic euglycemic clamp

intralipid Control

EXPERIMENTAL

Intralipid/Heparin co-infusion hyperinsulinemic euglycemic clamp among normal matched control subjects (control)

Drug: Intralipid/Heparin; Drug: Hyperinsulinemic euglycemic clamp

Interventions

Intralipid/Heparin DRUG

Co-infusion of intralipid and heparin solutions during a hyperinsulinemic euglycemic clamp

intralipid Control; intralipid FAOD

Glycerol/Saline DRUG

Co-infusion of a glycerol/saline solutions during a hyperinsulinemic euglycemic clamp

glycerol/saline Control; glycerol/saline FAOD

Hyperinsulinemic euglycemic clamp DRUG

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.

glycerol/saline Control; glycerol/saline FAOD; intralipid Control; intralipid FAOD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oregon Health and Science University: lead

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

VLCAD deficiency; Trifunctional Protein Deficiency With Myopathy And Neuropathy; Medium chain acyl CoA dehydrogenase deficiency; Carnitine Palmitoyltransferase II Deficiency, Late-Onset

Interventions

soybean oil, phospholipid emulsion; Heparin; Glycerol; Sodium Chloride

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Triose Sugar Alcohols; Sugar Alcohols; Alcohols; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Melanie Gillingham, PhD
• Organization: Oregon Health & Science University

gillingm@ohsu.edu

503-494-1682

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: August 7, 2015
• Study Start: February 1, 2016
• Primary Completion: January 1, 2021
• Study Completion: March 1, 2021
• Last Updated: January 30, 2024
• Results First Posted: January 30, 2024

Record last verified: 2023-12

Locations

US (1)