Trial Outcomes & Findings for Metabolic Effects of Switching Kaletra to Boosted Reyataz (NCT NCT00413153)

NCT ID: NCT00413153

Last Updated: 2010-03-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 15 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2010-03-09

Participant Flow

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.

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.

Participant milestones

Measure	Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) Kaletra (pre-study dose)
Overall Study STARTED	7	8
Overall Study COMPLETED	5	7
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) Kaletra (pre-study dose)
Overall Study Withdrawal by Subject	1	1
Overall Study Adverse Event	1	0

Baseline Characteristics

Metabolic Effects of Switching Kaletra to Boosted Reyataz

Baseline characteristics by cohort

Measure	Boosted Reyataz (ATV/r) n=7 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=8 Participants Kaletra (pre-study dose)	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	46 years STANDARD_DEVIATION 8 • n=5 Participants	50 years STANDARD_DEVIATION 6 • n=7 Participants	48 years STANDARD_DEVIATION 7 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Only data from subjects with 0 and 6 month Positron Emission Tomography (PET) scans were analyzed.

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.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=6 Participants Kaletra (pre-study dose)
Glucose Trafficking	26.7 umol/kg/min Standard Deviation 8.1	24.4 umol/kg/min Standard Deviation 17.7

SECONDARY outcome

Timeframe: 6 months

Population: Repeated measures analysis using all available data points for each participant

6 month mean and standard deviation for insulin-stimulated glucose uptake (M) per unit insulin at 120 minutes as measured by euglycemic hyperinsulinemic clamp.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Insulin Sensitivity	39.0 umol/kg/min per uU/mL insulin Standard Deviation 17.7	49.2 umol/kg/min per uU/mL insulin Standard Deviation 22.5

SECONDARY outcome

Timeframe: 6 months

Population: Repeated measures analysis using all available data points for each participant

6 month mean and standard deviation for fasting glucose.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Fasting Glucose	84 mg/dL Standard Deviation 7	90 mg/dL Standard Deviation 21

SECONDARY outcome

Timeframe: 6 months

Population: Repeated measures analysis using all available data points for each participant

6 month mean and standard deviation for serum triglyceride.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Lipid Metabolism - Serum Triglyceride	147 mg/dL Standard Deviation 92	209 mg/dL Standard Deviation 87

SECONDARY outcome

Timeframe: 6 months

Population: Data from participants with 0 \& 6 month data analyzed.

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).

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Body Composition - Visceral Adipose Tissue	91 square centimeters Standard Deviation 34	167 square centimeters Standard Deviation 61

SECONDARY outcome

Timeframe: 6 months

Population: Repeated measures analysis using all available data points for each participant

6 month mean and standard deviation for CD4+ count.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Immune Parameters -- CD4 Count	432 cells/microL Standard Deviation 192	688 cells/microL Standard Deviation 230

SECONDARY outcome

Timeframe: 6 months

Population: Repeated measures analysis using all available data points for each participant

6 month mean and standard deviation for AST.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Liver Enzymes -- Aspartate Aminotransferase (AST)	39 U/L Standard Deviation 29	42 U/L Standard Deviation 29

SECONDARY outcome

Timeframe: 6 months

Population: Repeated measures analysis using all available data points for each participant

6 month mean and standard deviation for ALT.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Liver Enzymes -- Alanine Aminotransferase (ALT)	61 U/L Standard Deviation 29	65 U/L Standard Deviation 34

SECONDARY outcome

Timeframe: 6 months

Population: Repeated measures analysis using all available data points for each participant

6 month mean and standard deviation for total bilirubin.

Outcome measures

Measure	Boosted Reyataz (ATV/r) n=5 Participants Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=7 Participants Kaletra (pre-study dose)
Total Bilirubin	2.8 mg/dL Standard Deviation 2.7	0.6 mg/dL Standard Deviation 0.3

Adverse Events

Boosted Reyataz (ATV/r)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Continue Kaletra (LPV/r)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Boosted Reyataz (ATV/r) n=7 participants at risk Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=8 participants at risk Kaletra (pre-study dose)
Gastrointestinal disorders Giardia Lamblia Infection	14.3% 1/7 • Number of events 1 • 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.	0.00% 0/8 • 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.
General disorders Mental Status Changes	14.3% 1/7 • Number of events 1 • 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.	0.00% 0/8 • 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.

Other adverse events

Measure	Boosted Reyataz (ATV/r) n=7 participants at risk Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Continue Kaletra (LPV/r) n=8 participants at risk Kaletra (pre-study dose)
Skin and subcutaneous tissue disorders cellulitis	14.3% 1/7 • 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.	0.00% 0/8 • 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.
Gastrointestinal disorders hyperbilirubinemia	85.7% 6/7 • 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.	0.00% 0/8 • 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.
Infections and infestations HIV RNA Copy Number Increased	14.3% 1/7 • 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.	0.00% 0/8 • 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.
Skin and subcutaneous tissue disorders rash	14.3% 1/7 • 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.	0.00% 0/8 • 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.
Gastrointestinal disorders transaminitis	14.3% 1/7 • 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.	0.00% 0/8 • 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.
Metabolism and nutrition disorders Type 2 Diabetes Mellitus	0.00% 0/7 • 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.	12.5% 1/8 • 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.

Additional Information

Steven K. Grinspoon, MD

Massachusetts General Hospital

Phone: 617-724-9109

Email: sgrinspoon@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60