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The Effects of Statin Therapy on Coronary Flow Reserve and Inflammatory Markers in HIV-Positive Patients

Primary Purpose

Human Immunodeficiency Virus (HIV), Cardiovascular Disease (CVD)

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Rosuvastatin
Sponsored by
Ottawa Heart Institute Research Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Human Immunodeficiency Virus (HIV) focused on measuring Human immunodeficiency virus (HIV), Statin therapy, Cardiovascular disease (CVD), Coronary Flow Reserve (CFR), Positron Emission Tomography (PET), Myocardial contrast echocardiography (MCE)

Eligibility Criteria

40 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 40-90 years of age
  • documented evidence of HIV infection
  • on standard antiretroviral therapy(ART) for >1 years
  • viral load persistently below the limits of detection while on ART
  • current Cluster of Differentiation Antigen 4 (CD4) count >350 cells/microlitre
  • baseline Framingham risk score of 10-20%

Exclusion Criteria:

  • uncontrolled diabetes mellitus (glycated hemoglobin (HbA1C) >6.5% or fasting glucose >7.0 mmol/L)
  • uncontrolled hypertension (systolic blood pressure >160 or diastolic blood pressure >90)
  • known coronary artery disease (CAD) e.g. previous myocardial infarction, revascularization procedure, or history of angina
  • chronic renal failure (glomerular filtration rate (GFR) <60 ml/min)
  • total cholesterol >5.8 mmol/L
  • Low-density lipoprotein (LDL) cholesterol >4.0 mmol/L
  • already receiving a statin for baseline dyslipidemia
  • pregnant or lactating
  • active untreated Hepatitis B or C
  • diagnosis or clinical evidence of a concomitant inflammatory/autoimmune disease
  • patients at baseline demonstrating regional perfusion abnormalities (confined to individual coronary territories) following stress MCE will be excluded and further management will be according to local best practice guidelines

Sites / Locations

  • The Ottawa Hospital-General Campus
  • University of Ottawa Heart Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Rosuvastatin

No rosuvastatin

Arm Description

Rosuvastatin 10mg once daily for 6 months.

No rosuvastatin- this group will continue with their current medical therapy for 6 months.

Outcomes

Primary Outcome Measures

Correlation between coronary flow reserve (CFR) and maximum target to background ratio (TBRmax).
At baseline, correlation between CFR by MCE and vascular inflammation (TBRmax) by FDG-PET/CT will be assessed. We anticipate good overall concurrence.

Secondary Outcome Measures

Change in CFR
Changes in CFR as measured by MCE will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin. Our study will be one of the first to examine the effects of rosuvastatin on measures of both inflammation and CFR in HIV+ patients.
Change in TBRmax.
Changes in vascular inflammation (TBRmax) as measured by FDG-PET/CT will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin.
Change in neurocognitive function
Changes in neurocognitve function as measured by a neuropsychological test battery (AMS-III Spatial Span, WAIS-R Digit Symbol, Hopkins Verbal Learning Test, Grooved Pegboard, Trail Making Tests A&B, Letter Numbering Sequencing , Patient's Assessment of Own Functioning, Center for Epidemiologic Studies-Depression Scale) will be evaluated over six months .

Full Information

First Posted
August 20, 2014
Last Updated
October 3, 2018
Sponsor
Ottawa Heart Institute Research Corporation
Collaborators
Ontario HIV Treatment Network
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1. Study Identification

Unique Protocol Identification Number
NCT02234492
Brief Title
The Effects of Statin Therapy on Coronary Flow Reserve and Inflammatory Markers in HIV-Positive Patients
Official Title
The Effects of Statin Therapy on Coronary Flow Reserve and Inflammatory Markers in HIV-Positive Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
October 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ottawa Heart Institute Research Corporation
Collaborators
Ontario HIV Treatment Network

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether the use of rosuvastatin in Human Immunodeficiency Virus (HIV) infected individuals lowers inflammation in blood vessels, improves blood circulation in the small arteries that provide nutrients to the heart muscle and improves neurocognitive function.
Detailed Description
HIV is a chronic inflammatory disease. Patients with HIV are at a high risk of cardiovascular disease (CVD) which may be related to this state of chronic inflammation. HIV infected individuals are at up to four times higher risk of suffering a heart attack (also know as acute coronary syndrome). The medicine rosuvastatin, commonly used to treat high cholesterol, has been shown to reduce inflammation in arteries in the general population and also in patients with high risk for heart problems. 72 subjects with HIV infection will be enrolled and divided into 2 groups of 36. Group 1: Treatment Group: Participants will receive a low dose of rosuvastatin, 10mg, for 6 months in addition to their current medical therapy. Group 2: Control Group: Participants will not receive rosuvastatin for 6 months and will continue with their current medical therapy. Participants in both groups will undergo blood tests, Myocardial Contrast Echocardiography (MCE) scan and a Positron Emission Tomography/Computed Tomography PET/CT scan using a radioactive tracer called fluorodeoxyglucose (FDG-PET), monocyte and serum cytokine studies at baseline and 6 months. 10 subjects without HIV will also be enrolled to undergo monocyte and serum cytokine blood tests only, for comparison.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus (HIV), Cardiovascular Disease (CVD)
Keywords
Human immunodeficiency virus (HIV), Statin therapy, Cardiovascular disease (CVD), Coronary Flow Reserve (CFR), Positron Emission Tomography (PET), Myocardial contrast echocardiography (MCE)

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rosuvastatin
Arm Type
Active Comparator
Arm Description
Rosuvastatin 10mg once daily for 6 months.
Arm Title
No rosuvastatin
Arm Type
No Intervention
Arm Description
No rosuvastatin- this group will continue with their current medical therapy for 6 months.
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Other Intervention Name(s)
Crestor
Intervention Description
Comparison of rosuvastatin to no rosuvastatin
Primary Outcome Measure Information:
Title
Correlation between coronary flow reserve (CFR) and maximum target to background ratio (TBRmax).
Description
At baseline, correlation between CFR by MCE and vascular inflammation (TBRmax) by FDG-PET/CT will be assessed. We anticipate good overall concurrence.
Time Frame
At baseline
Secondary Outcome Measure Information:
Title
Change in CFR
Description
Changes in CFR as measured by MCE will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin. Our study will be one of the first to examine the effects of rosuvastatin on measures of both inflammation and CFR in HIV+ patients.
Time Frame
At 6 months
Title
Change in TBRmax.
Description
Changes in vascular inflammation (TBRmax) as measured by FDG-PET/CT will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin.
Time Frame
At 6 months
Title
Change in neurocognitive function
Description
Changes in neurocognitve function as measured by a neuropsychological test battery (AMS-III Spatial Span, WAIS-R Digit Symbol, Hopkins Verbal Learning Test, Grooved Pegboard, Trail Making Tests A&B, Letter Numbering Sequencing , Patient's Assessment of Own Functioning, Center for Epidemiologic Studies-Depression Scale) will be evaluated over six months .
Time Frame
At 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 40-90 years of age documented evidence of HIV infection on standard antiretroviral therapy(ART) for >1 years viral load persistently below the limits of detection while on ART current Cluster of Differentiation Antigen 4 (CD4) count >350 cells/microlitre baseline Framingham risk score of 10-20% Exclusion Criteria: uncontrolled diabetes mellitus (glycated hemoglobin (HbA1C) >6.5% or fasting glucose >7.0 mmol/L) uncontrolled hypertension (systolic blood pressure >160 or diastolic blood pressure >90) known coronary artery disease (CAD) e.g. previous myocardial infarction, revascularization procedure, or history of angina chronic renal failure (glomerular filtration rate (GFR) <60 ml/min) total cholesterol >5.8 mmol/L Low-density lipoprotein (LDL) cholesterol >4.0 mmol/L already receiving a statin for baseline dyslipidemia pregnant or lactating active untreated Hepatitis B or C diagnosis or clinical evidence of a concomitant inflammatory/autoimmune disease patients at baseline demonstrating regional perfusion abnormalities (confined to individual coronary territories) following stress MCE will be excluded and further management will be according to local best practice guidelines
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Girish Dwivedi, MD MRCP PhD
Organizational Affiliation
University of Ottawa Heart Institute, Harry Perkins Institute of Medical Research
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Gary Small, MD MRCP
Organizational Affiliation
Ottawa Heart Institute Research Corporation
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital-General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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The Effects of Statin Therapy on Coronary Flow Reserve and Inflammatory Markers in HIV-Positive Patients

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