NCT00965185

Brief Summary

In HIV patients, statin therapy will attenuate plaque inflammation, thus, making plaques less vulnerable, will deter plaque progression, and improve endothelial function. In addition to known cholesterol-lowering and C-reactive protein lowering effects, immunomodulatory effects of statins will lead to a shift from pro-inflammatory monocyte and T cell subsets to less atherogenic subpopulations.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Sep 2009

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 25, 2009

Completed
7 days until next milestone

Study Start

First participant enrolled

September 1, 2009

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2014

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

February 26, 2015

Completed
Last Updated

December 11, 2017

Status Verified

November 1, 2017

Enrollment Period

4.3 years

First QC Date

August 24, 2009

Results QC Date

January 30, 2015

Last Update Submit

November 9, 2017

Conditions

Cardiovascular DiseaseHIVAtherosclerosisInflammationStatins, HMG-CoAHIV Infections

Keywords

Cardiovascular DiseaseHIVAtherosclerosisInflammationStatinstreatment experienced

Outcome Measures

Primary Outcomes (1)

  • Coronary and Aortic Plaque Inflammation

    12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)

    Measured at baseline and 1 year

Secondary Outcomes (7)

  • Plaque Progression

    Measured at baseline and 1 year

  • Endothelial Function

    1 year

  • Immune Function

    Measured at baseline and 1 year

  • Lipid Profile

    Measured at baseline and 1 year

  • C-reactive Protein (CRP)

    Measured at baseline and 1 year

  • +2 more secondary outcomes

Study Arms (2)

Atorvastatin

EXPERIMENTAL

20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.

Drug: atorvastatin

placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

atorvastatinDRUG

20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.

Atorvastatin
PlaceboDRUG

Placebo

placebo

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Men and women age 18-60 with previously diagnosed HIV disease
  • Subclinical coronary artery disease as defined by presence of one or more plaque on coronary CTA without history of cardiac events or cardiac symptoms and no evidence of critical coronary stenosis. Target to background ratio (TBR) as determined by PET of \> 1.6.
  • Stable anti-retroviral (ARV) therapy as defined by no changes in ARV regimen for \>6 months
  • LDL-cholesterol \>70 mg/dL and \<130 mg/dL

You may not qualify if:

  • History of acute coronary syndrome
  • Contraindication to statin therapy
  • Current statin use
  • AST or ALT two times greater than the upper limit of normal or receiving treatment for active liver disease
  • Renal disease or creatinine \>1.5 mg/dL (given the risk of contrast nephropathy during CT angiography of the heart)
  • Infectious illness within past 3 months
  • Contraindication to beta-blocker (including moderate to severe asthma or heart block) or nitroglycerin use as these drugs are given as part of the standard cardiac CT protocol. Previous allergic reaction to beta blocker or nitroglycerin.
  • Body weight greater than 300 lbs due to CT scanner table limitations
  • Patients with previous allergic reactions to iodine-containing contrast media
  • Active illicit drug use
  • Patients who report any significant radiation exposure over the course of the year prior to randomization. Significant exposure is defined as:
  • More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization
  • More than 2 myocardial perfusion studies within the past 12 months
  • More than 2 CT angiograms within the past 12 months
  • Any subjects with history of radiation therapy.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

  • Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, Williams KC, Lo J, Grinspoon SK. Arterial inflammation in patients with HIV. JAMA. 2012 Jul 25;308(4):379-86. doi: 10.1001/jama.2012.6698.

    PMID: 22820791BACKGROUND

  • Lo J, Lu MT, Ihenachor EJ, Wei J, Looby SE, Fitch KV, Oh J, Zimmerman CO, Hwang J, Abbara S, Plutzky J, Robbins G, Tawakol A, Hoffmann U, Grinspoon SK. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2015 Feb;2(2):e52-63. doi: 10.1016/S2352-3018(14)00032-0. Epub 2015 Jan 9.

    PMID: 26424461RESULT

  • deFilippi C, Christenson R, Joyce J, Park EA, Wu A, Fitch KV, Looby SE, Lu MT, Hoffmann U, Grinspoon SK, Lo J. Brief Report: Statin Effects on Myocardial Fibrosis Markers in People Living With HIV. J Acquir Immune Defic Syndr. 2018 May 1;78(1):105-110. doi: 10.1097/QAI.0000000000001644.

    PMID: 29419569DERIVED

MeSH Terms

Conditions

Cardiovascular DiseasesAtherosclerosisInflammationHIV Infections

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

PyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeptanoic AcidsFatty AcidsLipids

Limitations and Caveats

FDG-PET scan data was interpretable in only a limited subset of participants as a result of technical problems with manual co-registration (outcome 1). We were unable to collect data for endothelial function due to equipment malfunction (outcome 3).

Results Point of Contact

Title
Dr. Steven K Grinspoon
Organization
Massachusetts General Hospital
sgrinspoon@mgh.harvard.edu
617-724-9109

Study Officials

  • Steven K. Grinspoon, MD

    Massachusetts General Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine, Harvard Medical School

Study Record Dates

First Submitted

August 24, 2009

First Posted

August 25, 2009

Study Start

September 1, 2009

Primary Completion

January 1, 2014

Study Completion

January 1, 2014

Last Updated

December 11, 2017

Results First Posted

February 26, 2015

Record last verified: 2017-11

Locations

US(1)