MedTrace Logo

Mechanism of Fatty Acid-induced Impairment of Glucose-simulated Insulin Secretion - Effect of Buphenyl

NCT00533559 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2010-06-25

No results posted yet for this study

Summary

An increase of plasma free fatty acids impairs insulin secretion and insulin sensitivity, thereby playing an important role in causing type 2 diabetes. Lipotoxicity plays an important role in the progression from normal glucose tolerance to fasting hyperglycemia and coversion to frank type 2 diabetes. A recent publication in the journal Science showed that buphenyl, when given to obese diabetic mice, resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease and inhancement of insulin action in liver, muscle and adipose tissue. the mechanism of action is believed to be due to reduction of endoplasmic reticulum (ER) stress. Buphenyl is currently approved for the treatment of rare inherited disorders of the urea cycle. We plan to administer Buphenyl orally to humans at a dose far lower than that used for the treatment of urea cycle disorders for 2 weeks prior to the testing of pancreatic function. One potential mechanism whereby chromically elevated plasma FFAs and glucose impairment beta cell function and insuln sensitivity is by ER stress and this can be prevented by administeration of buphenyl.

Conditions

Interventions

DRUG

sodium phenylbutyrate

buphenyl, 7.5 gm/day for two weeks for two studies, one with saline and one admission with intralipid and heparin

DRUG

Placebo

Placebo comparator

Sponsors & Collaborators

  • University Health Network, Toronto

    lead OTHER

Principal Investigators

  • Gary F. Lewis, MD · University Health Network, Toronto General Hospital

Study Design

Allocation
RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE
Model
PARALLEL

Eligibility

Min Age
35 Years
Max Age
60 Years
Sex
MALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2007-09-30
Primary Completion
2009-12-31
Completion
2010-03-31

Countries

  • Canada

Study Locations

More Related Trials

Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00533559 on ClinicalTrials.gov