CompletedNCT00965185Updated Dec 11, 2017Results posted

Statin Therapy to Improve Atherosclerosis in HIV Patients

An interventional study of atorvastatin and Placebo in Cardiovascular Disease, HIV and Atherosclerosis, sponsored by Massachusetts General Hospital. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2017-12-11.

Sponsored by Massachusetts General Hospital · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 40
Allocation: Randomized
Ages: 18 Years to 60 Years
Sex: All

Study 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.

Conditions studied

Cardiovascular Disease
HIV
Atherosclerosis
Inflammation
Statins, HMG-CoA
HIV Infections

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Keywords

Cardiovascular Disease
HIV
Atherosclerosis
Inflammation
Statins
treatment experienced

In context

Cardiovascular Diseases

4,904 studies on the registry are indexed under Cardiovascular Diseases; 920 are open to participants now.

This study's enrollment of 40 is below the median of 100 across 2,738 interventional studies indexed under Cardiovascular Diseases.

Browse Cardiovascular Diseases studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 60 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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

Exclusion criteria

Exclusion criteria:

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:
1. More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization
2. More than 2 myocardial perfusion studies within the past 12 months
3. More than 2 CT angiograms within the past 12 months
4. 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

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 40 participants (actual)

Study arms

Experimental
Atorvastatin
20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.
Drug: atorvastatin
Placebo comparator
placebo
Drug: Placebo

Interventions

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

What researchers measure

Primary outcomes

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

Secondary outcomes

Plaque Progression
12 month percent change in plaque volume
Time frame: Measured at baseline and 1 year
Endothelial Function
Assessment of endothelial function was to be measured by endothelial vasodilator function.
Time frame: 1 year
Immune Function
12 month change in CD4 T-lymphocytes
Time frame: Measured at baseline and 1 year
Lipid Profile
12 month change in lipid profile
Time frame: Measured at baseline and 1 year
C-reactive Protein (CRP)
12 month change in Log CRP concentration
Time frame: Measured at baseline and 1 year
Adipocytokines
12 month change in IL-6
Time frame: 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
Time frame: Measured at baseline, 1, 3, 6, 9, and 12 months

Results

Posted Feb 26, 2015

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).

Participant flow

This study enrolled men and women with HIV disease, no history of cardiovascular disease or cardiac symptoms, and evidence of subclinical atherosclerosis at Massachusetts General Hospital in Boston, MA USA. The study was done from November, 2009 to January, 2014.

Participant flow — Overall Study
Milestone	Atorvastatin	Placebo
Started	19	21
1 month visit	18	21
3 month visit	18	21
6 month visit	18	21
9 month visit	18	21
Completed	17	20
Not completed	2	1
Withdrew: Lost to follow-up	2	0
Withdrew: Withdrawal by subject	0	1

Outcome measures

PrimaryCoronary and Aortic Plaque Inflammation

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

Time frame:: Measured at baseline and 1 year
Reported as:: Mean · ratio

Coronary and Aortic Plaque Inflammation
ratio	Atorvastatin	Placebo
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)

SecondaryPlaque Progression

12 month percent change in plaque volume

Time frame:: Measured at baseline and 1 year
Reported as:: Mean · Percent change

Plaque Progression
Percent change	Atorvastatin	Placebo
12 month change in total plaque volume	-4.7 (-25.4 to 15.9)	18.2 (1.5 to 59.9)
12 month change in non-calcified plaque volume	-19.4 (-39.2 to 9.3)	20.4 (-7.1 to 94.4)

SecondaryEndothelial Function

Assessment of endothelial function was to be measured by endothelial vasodilator function.

Time frame:: 1 year

No measurements were reported for this outcome.

SecondaryImmune Function

12 month change in CD4 T-lymphocytes

Time frame:: Measured at baseline and 1 year
Reported as:: Mean · cells per microliter

Immune Function
cells per microliter	Atorvastatin	Placebo
Immune Function	17 (-68 to 101)	4 (-72 to 80)

SecondaryLipid Profile

12 month change in lipid profile

Time frame:: Measured at baseline and 1 year
Reported as:: Mean · mmol/L

Lipid Profile
mmol/L	Atorvastatin	Placebo
12 month change in total cholesterol	-1.23 (-1.53 to -0.93)	0.12 (-0.12 to 0.37)
12 month change in HDL cholesterol	0.02 (-0.11 to 0.16)	-0.04 (-0.17 to 0.09)
12 month change in direct LDL	-1.00 (-1.38 to 0.61)	0.30 (0.04 to 0.55)
12 month change in triglycerides	-0.10 (-0.46 to 0.44)	0.08 (-0.46 to 0.38)

SecondaryC-reactive Protein (CRP)

12 month change in Log CRP concentration

Time frame:: Measured at baseline and 1 year
Reported as:: Mean · log(mg/L)

C-reactive Protein (CRP)
log(mg/L)	Atorvastatin	Placebo
C-reactive Protein (CRP)	-0.3 (-0.6 to 0.0)	0.1 (-0.2 to 0.3)

SecondaryAdipocytokines

12 month change in IL-6

Time frame:: Measured at baseline and 1 year
Reported as:: Mean · pg/ml

Adipocytokines
pg/ml	Atorvastatin	Placebo
Adipocytokines	-1.25 (-2.90 to 0.40)	0.41 (-0.44 to 1.26)

SecondaryLiver 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

Time frame:: Measured at baseline, 1, 3, 6, 9, and 12 months
Reported as:: Number · participants

Liver Function Tests (LFTs)
participants	Atorvastatin	Placebo
Liver Function Tests (LFTs)	3	2

Adverse events

Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Atorvastatin	—	2/19 (10.5%)	13/19 (68.4%)
Placebo	—	1/21 (4.8%)	14/21 (66.7%)

Most frequent serious events

Most frequent serious events
Event	Atorvastatin	Placebo
Fallopian tube cystReproductive system and breast disorders	1/19	0/21
Gastrointestinal virus induced dehydrationGastrointestinal disorders	1/19	0/21
Hepatocellular carcinomaHepatobiliary disorders	0/19	1/21

Most frequent other events

Most frequent other events
Event	Atorvastatin	Placebo
Muscle aches or crampsMusculoskeletal and connective tissue disorders	6/19	5/21
Loose stoolsGastrointestinal disorders	3/19	1/21
Liver function test abnormalitiesHepatobiliary disorders	3/19	2/21
NauseaGastrointestinal disorders	1/19	2/21
Elevated fasting blood glucoseMetabolism and nutrition disorders	0/19	2/21
RashSkin and subcutaneous tissue disorders	0/19	1/21
Abdominal PainGeneral disorders	0/19	1/21

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Atorvastatin	Placebo	Total
<=18 years	0	0	0
Between 18 and 65 years	19	21	40
>=65 years	0	0	0

Age, Continuous
Age, Continuous(years)	Atorvastatin	Placebo	Total
Mean	52.2 ± 3.8	50.0 ± 5.6	51.1 ± 4.9

Sex: Female, Male
Sex: Female, Male(Participants)	Atorvastatin	Placebo	Total
Female	4	4	8
Male	15	17	32

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Atorvastatin	Placebo	Total
White	13	13	26
Black	3	3	6
Asian	0	1	1
Hispanic	1	1	2
More than one race	2	1	3
Unknown	0	2	2

Region of Enrollment
Region of Enrollment(participants)	Atorvastatin	Placebo	Total
United States	19	21	40

Study locations

1 site

Massachusetts General Hospital
Boston, Massachusetts 02114, United States

References and documents

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 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 11, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00965185
Lead sponsor: Massachusetts General Hospital
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Responsible party: Steven K. Grinspoon, MD (Professor of Medicine, Harvard Medical School, Massachusetts General Hospital) — Principal investigator
First posted: Aug 25, 2009
Start date: Sep 2009
Primary completion: Jan 2014
Completion: Jan 2014
Results posted: Feb 26, 2015
Last update: Dec 11, 2017

Study contacts

Steven K. Grinspoon, MD

principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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