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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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To study the effects of switching from Kaletra to Boosted Reyataz on glucose, lipids and fat in HIV-infected patients.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | Boosted Reyataz (300mg atazanavir + 100mg ritonavir) |
|
| 2 | Active Comparator | Kaletra (pre-study dose) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| atazanavir/ritonavir | Drug | atazanavir 300mg + ritonavir 100mg once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Fasting Glucose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven K Grinspoon, MD | MGH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19474651 | Derived | 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. |
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After screening visit to determine eligibility, subjects were asked to continue their current antiretroviral medications until the baseline visit, immediately after which they were randomized to continue lopinavir/ritonavir or switch to atazanavir/ritonavir.
Subjects were recruited through information given to HIV-care providers, postings in HIV-community organizations, newspaper advertisements, and the Massachusetts General Hospital research patient data registry. Recruitment began in March, 2006, and continued through May, 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Boosted Reyataz (ATV/r) | Boosted Reyataz (300mg atazanavir + 100mg ritonavir) |
| FG001 | Continue Kaletra (LPV/r) | Kaletra (pre-study dose) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Boosted Reyataz (ATV/r) | Boosted Reyataz (300mg atazanavir + 100mg ritonavir) |
| BG001 | Continue Kaletra (LPV/r) | Kaletra (pre-study dose) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Only data from subjects with 0 and 6 month Positron Emission Tomography (PET) scans were analyzed. | Posted | Mean | Standard Deviation | umol/kg/min | 6 months |
|
6 month study period
All subjects had physical examinations and were queried about any adverse event at each study visit (baseline, 2 weeks, 1 month, 2 months, 4 months, and 6 months), and bilirubin, ALT, ALT, CD4+ count, and HIV ultrasensitive viral load were sent at all of these timepoints.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Boosted Reyataz (ATV/r) | Boosted Reyataz (300mg atazanavir + 100mg ritonavir) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Giardia Lamblia Infection | Gastrointestinal disorders | MedDRA | Systematic Assessment | hospitalization required for Giardia lamblia infection |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| cellulitis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven K. Grinspoon, MD | Massachusetts General Hospital | 617-724-9109 | sgrinspoon@partners.org |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C000718687 | atazanavir, ritonavir drug combination |
| D061466 | Lopinavir |
| C558899 | lopinavir-ritonavir drug combination |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| lopinavir/ritonavir | Drug | patient remains on their pre-study dose of lopinavir/ritonavir |
|
|
6 month mean and standard deviation for fasting glucose.
| 6 months |
| Lipid Metabolism - Serum Triglyceride | 6 month mean and standard deviation for serum triglyceride. | 6 months |
| 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 |
| Immune Parameters -- CD4 Count | 6 month mean and standard deviation for CD4+ count. | 6 months |
| Liver Enzymes -- Aspartate Aminotransferase (AST) | 6 month mean and standard deviation for AST. | 6 months |
| Liver Enzymes -- Alanine Aminotransferase (ALT) | 6 month mean and standard deviation for ALT. | 6 months |
| Total Bilirubin | 6 month mean and standard deviation for total bilirubin. | 6 months |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Continue Kaletra (LPV/r) | Kaletra (pre-study dose) |
|
|
|
| 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. | Repeated measures analysis using all available data points for each participant | Posted | Mean | Standard Deviation | umol/kg/min per uU/mL insulin | 6 months |
|
|
|
|
| Secondary | Fasting Glucose | 6 month mean and standard deviation for fasting glucose. | Repeated measures analysis using all available data points for each participant | Posted | Mean | Standard Deviation | mg/dL | 6 months |
|
|
|
|
| Secondary | Lipid Metabolism - Serum Triglyceride | 6 month mean and standard deviation for serum triglyceride. | Repeated measures analysis using all available data points for each participant | Posted | Mean | Standard Deviation | mg/dL | 6 months |
|
|
|
|
| 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). | Data from participants with 0 & 6 month data analyzed. | Posted | Mean | Standard Deviation | square centimeters | 6 months |
|
|
|
|
| Secondary | Immune Parameters -- CD4 Count | 6 month mean and standard deviation for CD4+ count. | Repeated measures analysis using all available data points for each participant | Posted | Mean | Standard Deviation | cells/microL | 6 months |
|
|
|
|
| Secondary | Liver Enzymes -- Aspartate Aminotransferase (AST) | 6 month mean and standard deviation for AST. | Repeated measures analysis using all available data points for each participant | Posted | Mean | Standard Deviation | U/L | 6 months |
|
|
|
|
| Secondary | Liver Enzymes -- Alanine Aminotransferase (ALT) | 6 month mean and standard deviation for ALT. | Repeated measures analysis using all available data points for each participant | Posted | Mean | Standard Deviation | U/L | 6 months |
|
|
|
|
| Secondary | Total Bilirubin | 6 month mean and standard deviation for total bilirubin. | Repeated measures analysis using all available data points for each participant | Posted | Mean | Standard Deviation | mg/dL | 6 months |
|
|
|
|
| 2 |
| 7 |
| 6 |
| 7 |
| EG001 | Continue Kaletra (LPV/r) | Kaletra (pre-study dose) | 0 | 8 | 1 | 8 |
|
| Mental Status Changes | General disorders | MedDRA | Systematic Assessment | Mental status changes requiring hospitalization, found to be caused by combination of prescribed opiates |
|
| hyperbilirubinemia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| HIV RNA Copy Number Increased | Infections and infestations | MedDRA | Systematic Assessment |
|
| rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| transaminitis | Gastrointestinal disorders | MedDRA | Systematic Assessment | ALT and/or AST elevated to any degree above the upper limit of normal. |
|
| Type 2 Diabetes Mellitus | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
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| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |