Metabolic Effects of Switching Kaletra to Boosted Reyataz

HIV Infections Clinical Trial

Official title:

Metabolic Effects of Switching Kaletra to Boosted Reyataz

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00413153
• Other study ID #: 2005-P-002239
• Status: Completed
• Phase: N/A
• First received: December 15, 2006
• Last updated: March 5, 2010
• Start date: May 2006
• Est. completion date: December 2008

Study information

• Verified date: March 2010
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

To study the effects of switching from Kaletra to Boosted Reyataz on glucose, lipids and fat in HIV-infected patients.

Description:

The primary objective of this study is to determine tissue specific glucose trafficking in patients before and after switching from a regimen containing Lopinavir/ritonavir (LPV/r) to one containing atazanavir/ritonavir (ATV/r). Secondary outcome measures of interest will include insulin sensitivity determined by clamp testing, and lipid metabolism and hepatic glucose production assessed using stable isotope techniques. We hypothesize that switching protease inhibitor (PI) to ATV/r from LPV/r will result in direct increases in glucose uptake in muscle and visceral adipose tissue in association with improvements in overall whole body insulin sensitivity compared to remaining on LPV/r. We will complete a prospective randomized trial of Human Immunodeficiency Virus (HIV) infected patients who have been on a stable antiretroviral (ARV) regimen containing LPV/r for at least 6 months and who will be randomized to either switch to a regimen containing ATV/r or remain on LPV/r for 6 months. Each subject will complete Positron Emission Tomography (PET) 18-fluorodeoxyglucose (FDG) imaging during a hyperinsulinemic clamp study at baseline and 6 months after randomization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Previously diagnosed HIV infection

2. Age between 18-65 years

3. Stable antiviral regimen containing at least 2 nucleoside reverse transcriptase inhibitors (NRTI's) and LPV/r for ³ 6 mos

4. CD4 count > 400 cell/mm3

5. Metabolic complication as indicated by one or more of hyperinsulinemia (fasting insulin >= 15 mIU/ml), hypercholesteremia (fasting total cholesterol >= 200 mg/dL), hypertriglyceridemia (fasting triglycerides >= 150 mg/dL), or treatment with a lipid lowering medication.

Exclusion Criteria:

1. Hemoglobin < 11.0 g/dL

2. History of Diabetes Mellitus

3. Currently on medication for Diabetes

4. Therapy with glucocorticoid, growth hormone or other anabolic agents currently or within the past 3 months

5. Current substance abuse, including alcohol, cocaine and/or heroin

6. Any contraindication to ATV/r or known allergy to ATV

7. Concurrent therapy with: Bepridil; cisapride; ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine); indinavir; irinotecan; lovastatin; midazolam; pimozide; proton pump inhibitors (esomeprazole, lansoprazole, omeprazole); rifampin; simvastatin; St John's wort; or triazolam

8. New or serious opportunistic infection in the past 3 months

9. Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• atazanavir/ritonavir
atazanavir 300mg + ritonavir 100mg once daily
• lopinavir/ritonavir
patient remains on their pre-study dose of lopinavir/ritonavir

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glucose Trafficking	6 month mean and standard deviation for glucose uptake into anterior thigh muscle as measured by FDG/PET scanning during euglycemic hyperinsulinemic clamp. During the hyperinsulinemic conditions of the clamp, glucose and 18-FDG [labeled glucose] are taken up by muscle. The quantity of 18-FDG taken up is measured by the PET scan. Although there are no well-accepted norms for this measurement, a higher value indicates that more glucose is being taken up by (or "trafficked to") muscle. Increased uptake of glucose indicates increased muscle insulin sensitivity.	6 months	No
Secondary	Insulin Sensitivity	6 month mean and standard deviation for insulin-stimulated glucose uptake (M) per unit insulin at 120 minutes as measured by euglycemic hyperinsulinemic clamp.	6 months	No
Secondary	Fasting Glucose	6 month mean and standard deviation for fasting glucose.	6 months	No
Secondary	Lipid Metabolism - Serum Triglyceride	6 month mean and standard deviation for serum triglyceride.	6 months	No
Secondary	Body Composition - Visceral Adipose Tissue	6 month mean and standard deviation for visceral adipose tissue (VAT) as measured by single slice computed tomography (CT) scan at the L4 pedicle (pedicle of 4th lumbar vertebra).	6 months	No
Secondary	Immune Parameters -- CD4 Count	6 month mean and standard deviation for CD4+ count.	6 months	No
Secondary	Liver Enzymes -- Aspartate Aminotransferase (AST)	6 month mean and standard deviation for AST.	6 months	Yes
Secondary	Liver Enzymes -- Alanine Aminotransferase (ALT)	6 month mean and standard deviation for ALT.	6 months	Yes
Secondary	Total Bilirubin	6 month mean and standard deviation for total bilirubin.	6 months	Yes