Cardiovascular DiseaseNCT00965185

Statin Therapy to Improve Atherosclerosis in HIV Patients

A study testing atorvastatin in people with Cardiovascular Disease and HIV, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Cardiovascular Disease, HIV, Atherosclerosis
What is being tested?: atorvastatin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 40 participants
Where: 1 siteUnited States
Study dates: Sep 2009to Jan 2014
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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

Show all 18Show fewer

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.
Patients already scheduled or being considered for a procedure or treatment requiring significant radiation exposure (e.g., radiation therapy, PCI, or catheter ablation of arrhythmia) within 12 months of randomization
Pregnancy or breastfeeding
Coronary artery luminal narrowing >70% seen on coronary CTA

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients

Conditions: Cardiovascular Disease, HIV, Atherosclerosis, Inflammation, Statins, HMG-CoA, HIV Infections
Being tested: atorvastatin, Placebo
Keywords: Cardiovascular Disease, HIV, Atherosclerosis, Inflammation, Statins, treatment experienced
Medical subject headings: Cardiovascular Diseases, Atherosclerosis, Inflammation, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT00965185
Study group	Role	What they receive
Atorvastatin	Experimental	20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months. Receives: Drug: atorvastatin
placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Coronary and Aortic Plaque Inflammation
12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)
Measured: Measured at baseline and 1 year

Secondary outcomes (7)

Plaque Progression
12 month percent change in plaque volume
Measured: Measured at baseline and 1 year
Endothelial Function
Assessment of endothelial function was to be measured by endothelial vasodilator function.
Measured: 1 year
Immune Function
12 month change in CD4 T-lymphocytes
Measured: Measured at baseline and 1 year
Lipid Profile
12 month change in lipid profile
Measured: Measured at baseline and 1 year
C-reactive Protein (CRP)
12 month change in Log CRP concentration
Measured: Measured at baseline and 1 year
Adipocytokines
12 month change in IL-6
Measured: Measured at baseline and 1 year
Liver Function Tests (LFTs)
Number of participants with LFT abnormalities (greater than or equal to 3 times the upper limit of normal).
For reference, the normal ranges for AST and ALT are shown below. Please note that the normal range for ALT at Labcorp changed over the course of the study. AST and ALT elevations were determined based on the normal range at the time the lab test was performed.
ALT: 0-40 IU/L, 0-44 IU/L, or 0-55 IU/L AST: 0-40 IU/L
Measured: Measured at baseline, 1, 3, 6, 9, and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2009Jan 2014

First posted25 Aug 2009 (estimated)
Study startSep 2009
Primary completionJan 2014
Study completionJan 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00965185
Sponsor's protocol ID: 2008-P-000257
Other IDs: R01HL095123, HL 095123
Status last verified: Nov 2017
First submitted: 24 Aug 2009
Last updated: 11 Dec 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 22820791
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.
PubMed 26424461
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.
PubMed 29419569

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients
ClinicalTrials.gov ID: NCT00965185
Acronym / sponsor ID: 2008-P-000257
Conditions: Cardiovascular Disease, HIV, Atherosclerosis, Inflammation, Statins, HMG-CoA, HIV Infections
Keywords: Cardiovascular Disease, HIV, Atherosclerosis, Inflammation, Statins, treatment experienced
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: Sep 2009
Primary completion: Jan 2014 (actual)
Study completion: Jan 2014 (actual)
First posted: 25 Aug 2009 (estimated)
Results: Posted 26 Feb 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Atorvastatin	Experimental	Drug: atorvastatin20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.
placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (18 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
atorvastatin20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.	Drug	Atorvastatin
PlaceboPlacebo	Drug	placebo

Primary outcome

Coronary and Aortic Plaque Inflammation
Time frame: Measured at baseline and 1 year
12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)

7 secondary outcomes

Plaque Progression
Time frame: Measured at baseline and 1 year
Endothelial Function
Time frame: 1 year
Immune Function
Time frame: Measured at baseline and 1 year
Lipid Profile
Time frame: Measured at baseline and 1 year
C-reactive Protein (CRP)
Time frame: Measured at baseline and 1 year
Adipocytokines
Time frame: Measured at baseline and 1 year
Liver Function Tests (LFTs)
Time frame: Measured at baseline, 1, 3, 6, 9, and 12 months

Results and safety

Results posted to the registry on 26 Feb 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Atorvastatin	19	17
Placebo	21	20

Primary outcome: Coronary and Aortic Plaque Inflammation

Time frame: Measured at baseline and 1 year. Mean (95% Confidence Interval). Unit: ratio

Measure	Atorvastatin n = 10	Placebo n = 11
Mean FDG-PET TBR of aorta	0.04 (-0.08 to 0.16)	-0.05 (-0.28 to 0.17)
Mean FDG-PET TBR of most diseased segment of aorta	-0.03 (-0.17 to 0.12)	-0.06 (-0.25 to 0.13)

Population analysed: All participants with baseline and 12 month PET and CT scans of acceptable image quality to permit assessment of change over time in identical regions in serial scans. As a result, only a limited number of participants could be included.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Atorvastatin	2 of 19 (10.5%)	13 of 19 (68.4%)	Not reported
Placebo	1 of 21 (4.8%)	14 of 21 (66.7%)	Not reported

Limitations and caveats (from the sponsor): 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).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 22820791Subramanian 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.
Results publication: PubMed 26424461Lo 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.
Derived from this study: PubMed 29419569deFilippi 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Steven K. Grinspoon, MD principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing atorvastatin in people with Cardiovascular Disease and HIV, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Coronary and Aortic Plaque Inflammation (time frame: Measured at baseline and 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00965185, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2017.