Effect of the HIV Protease Inhibitors Atazanavir and Lopi... | NCT00720590

Studies
Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors

NCT00720590

Sponsor

Indiana University

Status

Completed

Last Update Posted

Oct 25, 2017Actual

Enrollment

30Actual

Phase

Not Applicable

Conditions

Endothelial Dysfunction

Interventions

Atazanavir
Lopinavir/ritonavir
Placebo

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

ID	Type	Description	Link
R01HL072711	U.S. NIH Grant/Contract		View source
R01HL072711-01	U.S. NIH Grant/Contract		View source

Status Module

Record Verification Date

Jul 2008

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Nov 2003

Primary Completion Date

Sep 2006Actual

Completion Date

Oct 2006Actual

First Submitted Date

Jul 21, 2008

First Submission Date that Met QC Criteria

Jul 21, 2008

First Posted Date

Jul 23, 2008Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Oct 23, 2017

Last Update Posted Date

Oct 25, 2017Actual

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief Summary

HIV protease inhibitors (PIs) are a class of antiretroviral drugs used to inhibit viral replication. They do so by interfering with a key step in the replication process. Some HIV PIs have been associated with an increased risk of adverse cardiovascular side effects. Further study is needed, however, to assess the full extent of effect of newer HIV PIs, including atazanavir and lopinavir/ritonavir, on cardiovascular disease risk. This study will compare the effects of atazanavir, lopinavir/ritonavir, and placebo on certain cardiovascular disease risk factors in healthy people without HIV.

Detailed Description

Antiretroviral therapy for HIV, particularly with the use of PIs, is associated with an increased risk of heart attack. Specific cardiovascular side effects seen with the use of some PIs include insulin resistance, abnormal blood lipid levels, and endothelial dysfunction (abnormalities in the cells that line the inner surface of blood vessels). Past studies have shown that treatment with indinavir, an older PI, results in significant endothelial dysfunction, which may be the main cause for the increase in cardiovascular risk. Indinavir is now seldom used in clinical practice, and the newer PIs atazanavir and combination lopinavir/ritonavir now account for nearly 70% of total PI use in the United States. It is not known what effect these new PIs have on endothelial dysfunction. This study will compare the effects of atazanavir, lopinavir/ritonavir, and placebo on certain cardiovascular disease risk factors, including abnormal glucose metabolism and endothelial dysfunction, in healthy people without HIV.

Participation in this study will last 4 weeks. All participants will undergo initial assessments that will include various vascular and metabolic evaluations. Body weight, height, basal heart rate, and systolic and diastolic blood pressure will also be measured. Participants will then be assigned randomly to receive 4 weeks of treatment with 400 mg of atazanavir per day plus placebo, 400 mg/100 mg of lopinavir/ritonavir twice per day plus placebo, or placebos for both drugs per day. Upon completing the 4 weeks of treatment, participants will repeat the initial assessments.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not Applicable

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

30Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Experimental	Participants will receive treatment with atazanavir and placebo lopinavir/ritonavir.	Drug: Atazanavir Drug: Placebo
2	Experimental	Participants will receive treatment with lopinavir/ritonavir and placebo atazanavir.	Drug: Lopinavir/ritonavir Drug: Placebo
3	Placebo Comparator	Participants will receive treatment with placebos for both drugs.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Atazanavir	Drug	400 mg of atazanavir (two 200-mg capsules) per day for 4 weeks	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Leg blood flow response to the intra-femoral artery infusion of methacholine chloride		Measured at Week 4

Secondary Outcomes

Measure	Description	Time Frame
Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study		Measured at Week 4

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy and lean with normal lipids
Not infected with HIV or viral hepatitis

Exclusion Criteria:

Accepts Healthy Volunteers

Yes

Sex

Male

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

65 Years

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Michael P. Dubé, MD	Indiana University	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Indiana University School of Medicine		Indianapolis	Indiana	46202	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
18636958	Result	Dube MP, Shen C, Greenwald M, Mather KJ. No impairment of endothelial function or insulin sensitivity with 4 weeks of the HIV protease inhibitors atazanavir or lopinavir-ritonavir in healthy subjects without HIV infection: a placebo-controlled trial. Clin Infect Dis. 2008 Aug 15;47(4):567-74. doi: 10.1086/590154.

ID	Term
D000069446	Atazanavir Sulfate
D061466	Lopinavir

ID	Term
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009842	Oligopeptides