The Study of HIV Protease Inhibitors and Their Effects on Glucose Metabolism
|First Received Date ICMJE||November 28, 2005|
|Last Updated Date||September 28, 2009|
|Start Date ICMJE||January 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Insulin secretion after a single dose of HIV protease inhibitor versus placebo (insulin secretion assessed by using the hyperglycemic clamp technique)|
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00259727 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||The Study of HIV Protease Inhibitors and Their Effects on Glucose Metabolism|
|Official Title ICMJE||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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||1|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||80|
|Completion Date||September 2008|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 72 Years|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00259727|
|Other Study ID Numbers ICMJE||RCD-005-05S|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Lee, Grace - Principal Investigator, Department of Veterans Affairs|
|Study Sponsor ICMJE||Department of Veterans Affairs|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Department of Veterans Affairs|
|Verification Date||March 2009|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP