The Study of HIV Protease Inhibitors and Their Effects on Glucose Metabolism
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ClinicalTrials.gov Identifier: NCT00259727 |
Recruitment Status
:
Completed
First Posted
: November 29, 2005
Last Update Posted
: September 30, 2009
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Condition or disease |
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Diabetes HIV Infections Insulin Resistance |
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.
Study Type : | Observational |
Estimated Enrollment : | 80 participants |
Official Title: | The Effects of HIV Protease Inhibitors on Glucose Metabolism |
Study Start Date : | January 2006 |
Actual Study Completion Date : | September 2008 |

Group/Cohort |
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1 |
- Insulin secretion after a single dose of HIV protease inhibitor versus placebo (insulin secretion assessed by using the hyperglycemic clamp technique)
- 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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Ages Eligible for Study: | 18 Years to 72 Years (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00259727
United States, California | |
VA Medical Center, San Francisco | |
San Francisco, California, United States, 94121 |
Principal Investigator: | Grace Lee, MD | VA Medical Center, San Francisco |
Publications of Results:
Responsible Party: | Lee, Grace - Principal Investigator, Department of Veterans Affairs |
ClinicalTrials.gov Identifier: | NCT00259727 History of Changes |
Other Study ID Numbers: |
RCD-005-05S |
First Posted: | November 29, 2005 Key Record Dates |
Last Update Posted: | September 30, 2009 |
Last Verified: | March 2009 |
Keywords provided by VA Office of Research and Development:
Amprenavir Glucagon HIV Protease inhibitors |
Indinavir Lopinavir Ritonavir |
Additional relevant MeSH terms:
HIV Infections Insulin Resistance Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Hyperinsulinism |
Glucose Metabolism Disorders Metabolic Diseases Protease Inhibitors HIV Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |