The Study of HIV Protease Inhibitors and Their Effects on Glucose Metabolism

This study has been completed.
Sponsor:
Information provided by:
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00259727
First received: November 28, 2005
Last updated: September 28, 2009
Last verified: March 2009

November 28, 2005
September 28, 2009
January 2006
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Insulin secretion after a single dose of HIV protease inhibitor versus placebo (insulin secretion assessed by using the hyperglycemic clamp technique)
  • 1. Insulin secretion after a single dose of HIV protease inhibitor versus placebo; insulin secretion assessed by using the hyperglycemic clamp technique
  • 2. Hepatic glucose production, glycogenolysis, and gluconeogenesis after a single dose of HIV protease inhibitor versus placebo; stable isotope analysis withmass isotopic distribution analysis.
  • 3. Hepatic glucose production during a somatostatininfusion in the fasting and hyperinsulinemic state after a single dose of HIV protease inhibitor.
Complete list of historical versions of study NCT00259727 on ClinicalTrials.gov Archive Site
  • Hepatic glucose production, glycogenolysis, and gluconeogenesis after a single dose of HIV protease inhibitor versus placebo (stable isotope analysis with mass isotopic distribution analysis)
  • Hepatic glucose production during a somatostatin infusion in the fasting and hyperinsulinemic state after a single dose of HIV protease inhibitor
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The Study of HIV Protease Inhibitors and Their Effects on Glucose Metabolism
The Effects of HIV Protease Inhibitors on Glucose Metabolism

The purpose of this study is to determine the mechanisms by which HIV protease inhibitors contribute to the development of diabetes in HIV-infected patients. The investigators propose that some HIV protease inhibitors impair insulin secretion and increase the production of glucose by the liver.

HIV protease inhibitors (PIs) have been associated with type 2 diabetes. To design future HIV drugs that have have the least adverse metabolic effects, it is necessary to identify the disorders of glucose metabolism with PI therapy. Previously PIs have been shown to acutely induce insulin resistance in the periphery. Preliminary data show that PIs also impair insulin secretion and increase hepatic glucose production in humans. These lesions are key contributors to the development of type 2 diabetes. Due to the difficulty in separating out factors related to HIV infection from the direct effect of PIs, an effective design is to study HIV-negative subjects to define the direct effects of PIs on the liver and pancreas on glucose metabolism:

Specific Aim 1: To determine which PIs acutely inhibit insulin secretion in humans; randomized, double-blind, placebo-controlled trials will be performed on healthy normal volunteers given either a single dose of PI or placebo using the hyperglycemic clamp to assess insulin secretion in relation to insulin sensitivity.

Specific Aim 2: To determine which PIs acutely increase hepatic glucose production, glycogenolysis, and gluconeogenesis; measurements will be assessed in the fasting and hyperinsulinemic states using stable isotope analysis techniques. Samples have already been collected from double-blind, placebo-controlled trials of the effects of a single dose of PI on insulin sensitivity during the euglycemic hyperinsulinemic clamp.

Specific Aim 3: To determine the mechanism by which certain PIs increase hepatic glucose production; an infusion of somatostatin during the fasting state and hyperinsulinemic state will be used to suppress the effects of glucagon. Subjects will undergo a randomized, double-blind, placebo-controlled trial of a single dose of PI or placebo on insulin sensitivity using the euglycemic hyperinsulinemic clamp. Somatostatin, glucagon, and growth hormone will be infused before and during the clamp study. Hepatic glucose production, glycogenolysis, and gluconeogenesis will be assessed using stable isotope tracer techniques. Results will be compared to PIs acutely given in the absence of somatostatin, as stated in Specific Aim 2.

Determination of the effects of PI therapy allows clinicians to identify patients who may be at particular risk for developing diabetes on certain PIs and treat them more effectively. In the future, drugs for the treatment of HIV can be developed that avoid these disorders of glucose metabolism.

Observational
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  • Diabetes
  • HIV Infections
  • Insulin Resistance
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1

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
September 2008
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Inclusion Criteria:

  • Healthy, HIV-negative volunteers between the ages of 18-72 years

Exclusion Criteria:

  • Any subject with states known to be associated with insulin resistance, such as impaired fasting glucose (glucose > 110 mg/dl), overweight (body mass index [BMI] > 27), dyslipidemia (triglycerides > 150 mg/dl), hypertension (blood pressure [BP] > 130/85 mmHg or on medication), renal disease, systemic use of glucocorticoids, growth hormone, niacin, or antipsychotics.
  • Women will be tested for pregnancy immediately prior to study and excluded if pregnant.
Both
18 Years to 72 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00259727
RCD-005-05S
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Lee, Grace - Principal Investigator, Department of Veterans Affairs
Department of Veterans Affairs
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Principal Investigator: Grace Lee, MD VA Medical Center, San Francisco
Department of Veterans Affairs
March 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP