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Metabolic Effects of Switching Kaletra to Boosted Reyataz

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00413153
First received: December 15, 2006
Last updated: March 5, 2010
Last verified: March 2010
  Purpose

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


Condition Intervention
HIV Infections
Drug: atazanavir/ritonavir
Drug: lopinavir/ritonavir

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Metabolic Effects of Switching Kaletra to Boosted Reyataz

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Glucose Trafficking [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    6 month mean and standard deviation for fasting glucose.

  • Lipid Metabolism - Serum Triglyceride [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    6 month mean and standard deviation for serum triglyceride.

  • Body Composition - Visceral Adipose Tissue [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    6 month mean and standard deviation for CD4+ count.

  • Liver Enzymes -- Aspartate Aminotransferase (AST) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    6 month mean and standard deviation for AST.

  • Liver Enzymes -- Alanine Aminotransferase (ALT) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    6 month mean and standard deviation for ALT.

  • Total Bilirubin [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    6 month mean and standard deviation for total bilirubin.


Enrollment: 15
Study Start Date: May 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Drug: atazanavir/ritonavir
atazanavir 300mg + ritonavir 100mg once daily
Other Name: Boosted Reyataz
Active Comparator: 2
Kaletra (pre-study dose)
Drug: lopinavir/ritonavir
patient remains on their pre-study dose of lopinavir/ritonavir
Other Name: Kaletra

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413153

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Bristol-Myers Squibb
Investigators
Principal Investigator: Steven K Grinspoon, MD MGH
  More Information

No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00413153     History of Changes
Other Study ID Numbers: 2005-P-002239
Study First Received: December 15, 2006
Results First Received: November 4, 2009
Last Updated: March 5, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
HIV
Kaletra
Reyataz
Insulin sensitivity
Lipids
Body Composition
Receiving Kaletra
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Atazanavir
Lopinavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014