Clinical trial NCT00413153: Metabolic Effects of Switching Kaletra to Boosted Reyataz
Official title: Metabolic Effects of Switching Kaletra to Boosted Reyataz
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: HIV
Kaletra
Reyataz
Insulin sensitivity
Lipids
Body Composition
Receiving Kaletra
Treatment Experienced
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2006-12-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Glucose Trafficking
timeFrame: 6 months
Secondary outcomes:
measure: Insulin Sensitivity
timeFrame: 6 months
measure: Fasting Glucose
timeFrame: 6 months
measure: Lipid Metabolism - Serum Triglyceride
timeFrame: 6 months
measure: Body Composition - Visceral Adipose Tissue
timeFrame: 6 months
measure: Immune Parameters -- CD4 Count
timeFrame: 6 months
measure: Liver Enzymes -- Aspartate Aminotransferase (AST)
timeFrame: 6 months
measure: Liver Enzymes -- Alanine Aminotransferase (ALT)
timeFrame: 6 months
measure: Total Bilirubin
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: MGH
name: Steven K Grinspoon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stanley TL, Joy T, Hadigan CM, Liebau JG, Makimura H, Chen CY, Thomas BJ, Weise SB, Robbins GK, Grinspoon SK. Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on muscle glucose uptake and visceral fat in HIV-infected patients. AIDS. 2009 Jul 17;23(11):1349-57. doi: 10.1097/QAD.0b013e32832ba904.