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Metabolic Effects of Switching Kaletra to Boosted Reyataz

Primary Purpose

HIV Infections

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
atazanavir/ritonavir
lopinavir/ritonavir
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, Kaletra, Reyataz, Insulin sensitivity, Lipids, Body Composition, Receiving Kaletra, Treatment Experienced

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

Boosted Reyataz (300mg atazanavir + 100mg ritonavir)

Kaletra (pre-study dose)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Fasting Glucose
6 month mean and standard deviation for fasting glucose.
Lipid Metabolism - Serum Triglyceride
6 month mean and standard deviation for serum triglyceride.
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).
Immune Parameters -- CD4 Count
6 month mean and standard deviation for CD4+ count.
Liver Enzymes -- Aspartate Aminotransferase (AST)
6 month mean and standard deviation for AST.
Liver Enzymes -- Alanine Aminotransferase (ALT)
6 month mean and standard deviation for ALT.
Total Bilirubin
6 month mean and standard deviation for total bilirubin.

Full Information

First Posted
December 15, 2006
Last Updated
March 5, 2010
Sponsor
Massachusetts General Hospital
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00413153
Brief Title
Metabolic Effects of Switching Kaletra to Boosted Reyataz
Official Title
Metabolic Effects of Switching Kaletra to Boosted Reyataz
Study Type
Interventional

2. Study Status

Record Verification Date
March 2010
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Massachusetts General Hospital
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV, Kaletra, Reyataz, Insulin sensitivity, Lipids, Body Composition, Receiving Kaletra, Treatment Experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Arm Title
2
Arm Type
Active Comparator
Arm Description
Kaletra (pre-study dose)
Intervention Type
Drug
Intervention Name(s)
atazanavir/ritonavir
Other Intervention Name(s)
Boosted Reyataz
Intervention Description
atazanavir 300mg + ritonavir 100mg once daily
Intervention Type
Drug
Intervention Name(s)
lopinavir/ritonavir
Other Intervention Name(s)
Kaletra
Intervention Description
patient remains on their pre-study dose of lopinavir/ritonavir
Primary Outcome Measure Information:
Title
Glucose Trafficking
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Insulin Sensitivity
Description
6 month mean and standard deviation for insulin-stimulated glucose uptake (M) per unit insulin at 120 minutes as measured by euglycemic hyperinsulinemic clamp.
Time Frame
6 months
Title
Fasting Glucose
Description
6 month mean and standard deviation for fasting glucose.
Time Frame
6 months
Title
Lipid Metabolism - Serum Triglyceride
Description
6 month mean and standard deviation for serum triglyceride.
Time Frame
6 months
Title
Body Composition - Visceral Adipose Tissue
Description
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).
Time Frame
6 months
Title
Immune Parameters -- CD4 Count
Description
6 month mean and standard deviation for CD4+ count.
Time Frame
6 months
Title
Liver Enzymes -- Aspartate Aminotransferase (AST)
Description
6 month mean and standard deviation for AST.
Time Frame
6 months
Title
Liver Enzymes -- Alanine Aminotransferase (ALT)
Description
6 month mean and standard deviation for ALT.
Time Frame
6 months
Title
Total Bilirubin
Description
6 month mean and standard deviation for total bilirubin.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Previously diagnosed HIV infection Age between 18-65 years Stable antiviral regimen containing at least 2 nucleoside reverse transcriptase inhibitors (NRTI's) and LPV/r for ³ 6 mos CD4 count > 400 cell/mm3 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: Hemoglobin < 11.0 g/dL History of Diabetes Mellitus Currently on medication for Diabetes Therapy with glucocorticoid, growth hormone or other anabolic agents currently or within the past 3 months Current substance abuse, including alcohol, cocaine and/or heroin Any contraindication to ATV/r or known allergy to ATV 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 New or serious opportunistic infection in the past 3 months Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven K Grinspoon, MD
Organizational Affiliation
MGH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19474651
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.
Results Reference
derived

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Metabolic Effects of Switching Kaletra to Boosted Reyataz

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